Synthesis and Crystal Structures of 4,5-Dihydroimidazo[1,5-b]pyrazol-6-ones

Key words

chloral - acetophenones - pyrazolines - heterocycles - imidazo­-[1,5-b]pyrazolones

Recent reviews on the synthesis and properties of heterocycles condensed to a pyrazole core have reported that these are an important source of bioactive molecules.[1] [2] Imidazopyrazoles have been recognized as substances of significant chemical, biological and medicinal interest.[3,4] By far, the most well-known compounds are those pertaining to the imidazo[1,2-b]pyrazole family, which have been described as possessing noteworthy anticancer,[4] [5] [6] antibacterial,[7] [8] and anti-inflammatory[9] [10] properties, among others. 5-Aminopyrazoles, the synthetic methods for which have been extensively reviewed,[11] are the main preparative intermediates for imidazo[1,2-b]pyrazoles.[12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] The synthesis and properties of imidazo[4,5-c]pyrazoles have also received considerable attention.[30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] 5-Aminopyrazoles have also been of great utility in preparing these compounds.[32] [33] [36] [40] [41] However, synthetic methodology for obtaining imidazo[1,5-b]pyrazole derivatives is notably lacking, and very little is known about these compounds.[3] [4] Only a few individual examples having this uncommon ring fusion have been previously prepared; for example, by cyclodehydration of substituted pyrazolylmethylacetamides leading to 2,3-dihydroimidazo[1,5-b] derivatives related to cyclized histamine,[43] preparation of 2,3-dihydro-1H-imidazo[1,5-b]pyrazole-4,6(3aH,5H)-dione from 1-(benzylideneamino)-5-(2-hydroxyethyl)hydantoin,[44] and the synthesis of hexahydro-4,4-dimethyl-1,3a-diaryl-6-oxo-1H-imidazo[1,5-b]pyrazole-3-carbonitriles from α-aminoisobutyrophenone phenyl hydrazones.[45] Concerning imidazopyrazolones, studies on the synthesis, properties and usefulness of substances exhibiting [1,2-b],[46] [47] [48] [49] [50] [4,5-c],[51] [52] and [3,4-b][45] ring systems have been successful. However, the synthesis of imidazo[1,5-b]pyrazol-6-ones remains to be achieved. To our knowledge, this paper describes the first synthetic approach to this class of compounds.

In an earlier work we synthesized novel 3-aryl-5-dichloromethyl-2-pyrazolines 5 starting from chloral, a cheap multipurpose starting material for organic synthesis,[53] and inexpensive, commercially available acetophenones. 2,2,2-Trichloroethylideneacetophenones 3 and 2,2-dichlorovinylacetophenones 4 were key intermediates (Scheme [1]).[54] [55] Taking into account the specific molecular arrangement of compounds 5 – two active centers of opposite polarity and the presence of an electrophilic dichloromethyl group attached to C-5 instead of the nucleophilic amino group present in 5-aminopyrazoles – we envisaged that compounds 5 could be of key interest as they offer privileged access to still unattainable imidazo[1,5-b]pyrazol-6-ones. The results of this study are detailed here, concluding in an effective method for preparing hitherto unknown 2-aryl-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-ones 10, as displayed in Scheme [2]. Pyrazolines 5 were treated with toluenesulfonyl isocyanate to obtain the corresponding toluenesulfonylaminocarbonyl intermediates 7, which were subjected to base treatment and directly provided the desired products (Table [1]). The scope of this method could also be extended by using aryl and alkyl isocyanates, which allowed the synthesis of the target 2,5-diaryl- and 5-alkyl-2-aryl-4,5-dihydroimidazo[1,5-b]pyrazol-6-ones 12 (Table [2]). It should be noted that, because of their utility for preparing a diversity of fused heterocyclic compounds, 5-aminopyrazoles have become key reagents for organic and medicinal chemistry.[56] However, these intermediates are not able to form an imidazo[1,5-b]pyrazole ring system. Conversely, we have overcome this limitation through 5-dichloromethylpyrazolines 5. Furthermore, these appear to be promising agents offering many other possibilities to prepare a wide variety of fused heterocycles.

Scheme 1 Synthesis of 5-dichloromethyl-2-pyrazolines 5 through chloral derivatives. Ar: (a) C₆H₅; (b) 4-ClC₆H₄; (c) 4-BrC₆H₄; (d) 4-MeC₆H₄; (e) 4-MeOC₆H₄; (f) 4-O₂NC₆H₄; (g) 4-PhC₆H₄; (h) 2-C₁₀H₇; (i) 2,4-Cl₂C₆H₃; (j) 3-BrC₆H₄

A series of 3-aryl-5-dichloromethyl-2-pyrazolines 5 was prepared by applying our previously reported synthetic method,[54] which involves preparation and dehydration of chloralacetophenones 2 to obtain the corresponding 2,2,2-trichloroethylideneacetophenones 3, selective electrochemical reduction[55] [57] to give dichlorovinylacetophenones 4, and treatment with hydrazine hydrate.

To investigate the first synthetic approach to products 10 through pyrazolines 5, compound 5d was selected as a model. Reaction with tosyl isocyanate led to the previously unknown 5-dichloromethyl-3-p-tolyl-N-tosyl-2-pyrazoline-1-carboxamide (7d; Ar = p-tolyl) in 96% yield (Scheme [2]). Next, a cyclization process promoted by strong bases, such as potassium tert-butoxide or lithium diisopropylamide, was attempted, but provided disappointing results, since complex mixtures of unidentifiable products were observed. However, on heating to reflux in triethylamine, the progressive formation of a single product was observed. This was isolated and spectroscopically identified as the hitherto unknown 2-(4-methylphenyl)-5-toluenesulfonyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10d; yield 65%), the molecular structure of which was confirmed by X-ray crystallographic analysis (Figure [1]).[58]

Figure 1 X-ray crystal structure of compound 10d (thermal ellipsoids drawn at the 50% probability level)

Scheme 2 Synthesis of 2-aryl-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-ones 10 from pyrazolines 5

In view of this successful result, products 10a, 10d, 10e, and 10h–j were similarly obtained from their respective precursors 7 in boiling triethylamine; however, other conversions required operating at higher reaction temperature using a sealed vessel under pressure (Table [1]). Successful results were also obtained with a more rapid and efficient one-pot preparative process. Thus, mixtures of compounds 5 with toluenesulfonyl isocyanate and triethylamine were heated at 130 °C for two hours, directly providing the desired products 10 in fair to good yields (Table [1]). It is clear that the formation of these products is explicable by initial generation of intermediates 7, which, under suitable basic experimental conditions, can undergo internal attack at the dichloromethyl group, leading to intermediates 8, the chemical evolution of which would occur by hydrogen chloride elimination to give intermediates 9. Finally, these would undergo an isomerization process to give the most stable products 10 (Scheme [2]).

Table 1 Preparation of Imidazo[1,5-b]pyrazol-6-ones 10

Entry	Intermediate 7	Yield (%)*	Product 10	Yield (%)*
a		97		50a (63)c
b		92		63b (75)c
c		92		38b (57)c
d		96		65a (70)c
e		97		46a (77)c
f		93		55b (88)c
g		98		60b (68)c
h		83		78a (82)c
i		70		80b (85)c
j		80		65a (82)c

* Isolated yield

^a At reflux temperature.

^b At 130 °C.

^c At 130 °C (one-pot process).

Once the synthesis of compounds 10 had been achieved, we focused on expanding the novel preparative method to obtain 2,5-diaryl- and 5-alkyl-2-aryl-4,5-dihydroimidazo[1,5-b]pyrazol-6-ones 12 by using aryl and alkyl isocyanates as acylating agents. Thus, reactions of a range of pyrazolines 5 with a variety of aryl and alkyl isocyanates were carried out to obtain novel derivatives 11 in moderate to good yields. The geometrical characteristics of these compounds­ were determined by X-ray crystallographic analysis of 5-dichloromethyl-N-(4-chlorophenyl)-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide (11f; Figure [2]).[59]

Figure 2 X-ray crystal structure of compound 11f (thermal ellipsoids drawn at the 50% probability level)

Cyclizations of intermediates 11 promoted by potassium tert-butoxide, diisopropylamide or triethylamine were ineffective. Conversely, employing DBU as base afforded good results for the targeted dihydroimidazo[1,5-b]pyrazol-6-ones 12, which were obtained in fair to good yields (Table [2]).

The molecular structure of one of these compounds: 5-(4-bromophenyl)-2-p-tolyl-4,5-dihydro-imidazo[1,5-b]-pyrazol-6-one (12h) was determined by X-ray crystallographic analysis (Figure [3]).[60]

To conclude, a new and highly flexible synthetic method for preparing imidazo[1,5-b]pyrazoles is reported that provides straightforward access to previously unattainable 4,5-dihydroimidazo[1,5-b]pyrazol-6-ones through 5-dichloro-methyl-2-pyrazolines. Given the previous scant progress in generating this type of ring fusion, these novel products are not only of high interest in themselves, but also in terms of exploring their possible biological properties. The development of syntheses for other classes of heterocyclic compounds by applying a similar strategy also appears feasible.

Table 2 Preparation of Imidazo[1,5-b]pyrazol-6-ones 12

Entry	Isocyanate	Intermediate 11	Yield (%)a	Product 12	Yield (%)a
a			50		40
b			43		70
c			51		53
d			74		70
e			70		75
f			70		83
g			72		62
h			71		64
i			63		51
j			61		54
k			60		50

^a Isolated yield.

Figure 3 X-ray crystal structure of compound 12h (thermal ellipsoids drawn at the 50% probability level)

NMR spectra were recorded with a Bruker AV-300 or Bruker AV-400 with tetramethylsilane as internal reference. High-resolution mass spectra (HRMS) were obtained with a time-of-flight (TOF) instrument equipped with electrospray ionization (ESI). IR spectra were recorded with Nicolet Impact 400 or Jasco FTIR-4700LE spectrophotometers. Microanalyses were performed with a Carlo Erba EA-1108 analyser. Melting points were determined with a Büchi Melting point B-540, and are uncorrected. 3-Aryl-5-dichloromethyl-2-pyrazolines 5 were prepared as previously described.[54]

Synthesis of 7; General Procedure

To a stirred suspension of compound 5 (2.5 mmol) in anhydrous diethyl ether (10 mL), a solution of toluenesulfonyl isocyanate (2.5 mmol) in anhydrous diethyl ether (10 mL) was slowly added dropwise (ca. 1 drop per second) under a nitrogen atmosphere. The stirring was continued for 10 min at r.t., and the precipitate was collected by filtration and crystallized from the appropriate solvent.

5-Dichloromethyl-3-phenyl-1-tosylaminocarbonyl-2-pyrazoline (7a)

Yield: 1.04 g (97%); white prisms; mp 168 °C (dec) (MeCN).

IR (Nujol): 3285, 1698, 1599, 1379, 1346, 1163, 1078, 895, 866, 848, 785, 673 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.44 (s, 3 H), 3.51 (dd, J = 18.3, 11.3 Hz, 1 H), 3.63 (dd, J = 18.3, 5.8 Hz, 1 H), 4.88 (ddd, J = 11.3, 5.8, 2.6 Hz, 1 H), 6.41 (d, J = 2.6 Hz, 1 H), 7.35 (d, J = 8.2 Hz, 2 H), 7.43–7.50 (m, 3 H), 7.72 (dd, J = 6.3, 1.8 Hz, 2 H), 7.99 (d, J = 8.2 Hz, 2 H), 8.67 (br s, 1 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.76 (CH₃), 35.15 (CH₂), 63.26 (CH), 71.11 (CHCl₂), 126.98 (CH), 128.42 (CH), 129.00 (CH), 129.62 (C), 129.67 (CH), 131.38 (CH), 136.04 (C), 145.00 (C), 148.41 (C=O), 155.12 (C=N).

MS: m/z (%) = 425 (0.5) [M]⁺, 427 (0.4) [M⁺+2], 228 (11), 197 (12), 155 (29), 145 (100), 128 (18), 91 (70), 77 (22).

Anal. Calcd for C₁₈H₁₇Cl₂N₃O₃S: C, 50.71; H, 4.02; N, 9.86; S, 7.52. Found: C, 50.83; H, 3.96; N, 9.85; S, 7.50.

5-Dichloromethyl-3-(4-chlorophenyl)-1-tosylaminocarbonyl-2-pyrazoline (7b)

Yield: 1.06 g (92%); white needles; mp 224 °C (dec) (MeCN).

IR (Nujol): 3330, 1706, 1600, 1408, 1346, 1166, 1087, 821, 785, 664 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.44 (s, 3 H), 3.47 (dd, J = 18.3, 11.3 Hz, 1 H), 3.59 (dd, J = 18.3, 5.8 Hz, 1 H), 4.88 (ddd, J = 11.3, 5.8, 2.6 Hz, 1 H), 6.40 (d, J = 2.6 Hz, 1 H), 7.34 (d, J = 8.3 Hz, 2 H), 7.41 (d, J = 8.6 Hz, 2 H), 7.66 (d, J = 8.6 Hz, 2 H), 7.99 (d, J = 8.3 Hz, 2 H), 8.74 (br s, 1 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.76 (CH₃), 35.05 (CH₂), 63.43 (CH), 71.03 (CHCl₂), 128.12 (C), 128.22 (CH), 128.42 (CH), 129.30 (CH), 129.68 (CH), 135.96 (C), 137.50 (C), 145.07 (C), 148.35 (C=O), 154.00 (C=N).

MS: m/z (%) = 459 (0.2) [M]⁺, 461 (0.2) [M⁺+2], 268 (10), 197 (20), 179 (100), 155 (35), 91 (77), 64 (20).

Anal. Calcd for C₁₈H₁₆Cl₃N₃O₃S: C, 46.92; H, 3.50; N, 9.12; S, 6.96. Found: C, 46.90; H, 3.49; N, 9.08; S, 7.00.

3-(4-Bromophenyl)-5-dichloromethyl-1-tosylaminocarbonyl-2-pyrazoline (7c)

Yield: 1.16 g (92%); white needles; mp 231 °C (dec) (MeCN).

IR (Nujol): 3331, 1706, 1593, 1404, 1347, 1166, 1072, 1009, 821, 784, 666 cm^–1.

¹H NMR (CDCl₃, 300 MHz): δ = 2.44 (s, 3 H), 3.47 (dd, J = 18.3, 11.1 Hz, 1 H), 3.59 (dd, J = 18.3, 6.0 Hz, 1 H), 4.88 (ddd, J = 11.1, 6.0, 2.4 Hz, 1 H), 6.40 (d, J = 2.4 Hz, 1 H), 7.58 (m, 4 H), 7.34 (d, J = 8.5 Hz, 2 H), 7.99 (d, J = 8.5 Hz, 2 H), 8.75 (br s, 1 H).

¹³C NMR (CDCl₃, 75.4 MHz): δ = 21.76 (CH₃), 35.00 (CH₂), 63.46 (CH), 71.03 (CHCl₂), 125.90 (C), 128.38 (CH), 128.42 (CH), 128.57 (C), 129.69 (CH), 132.26 (CH), 135.98 (C), 145.08 (C), 148.35 (C=O), 154.09 (C=N).

MS: m/z (%) = 503 (0.15) [M]⁺, 505 (0.18) [M⁺+2], 306 (7), 308 (11), 223 (85), 225 (77), 197 (34), 155 (61), 144 (82), 91 (100), 65 (32).

Anal. Calcd for C₁₈H₁₆BrCl₂N₃O₃S: C, 42.79; H, 3.19; N, 8.32; S, 6.35. Found: C, 42.81; H, 3.26; N, 8.30; S, 6.30.

5-Dichloromethyl-3-(4-methylphenyl)-1-tosylaminocarbonyl-2-pyrazoline (7d)

Yield: 1.06 g (96%); white prisms; mp 203 °C (dec) (MeCN).

IR (Nujol): 3293, 1696, 1350, 1168, 1072, 852, 782, 734, 668 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.40 (s, 3 H), 2.44 (s, 3 H), 3.48 (dd, J = 18.3, 11.2 Hz, 1 H), 3.59 (dd, J = 18.3, 5.6 Hz, 1 H), 4.85 (ddd, J = 11.2, 5.6, 2.3 Hz, 1 H), 6.41 (d, J = 2.3 Hz, 1 H), 7.25 (d, J = 7.8 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H), 7.61 (d, J = 7.8 Hz, 2 H), 7.99 (d, J = 8.1 Hz, 2 H), 8.71 (br s, 1 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.62 (CH₃), 21.75 (CH₃), 35.18 (CH₂), 63.16 (CH), 71.14 (CHCl₂), 126.85 (C), 126.94 (CH), 128.40 (CH), 129.65 (CH), 129.70 (CH), 136.07 (C), 141.96 (CH), 144.95 (C), 148.40 (C=O), 155.17 (C=N).

MS: m/z (%) = 439 (1) [M]⁺, 441 (0.8) [M⁺+2], 242 (34), 244 (21), 197 (45), 159 (100), 155 (63), 132 (38), 115 (30), 91 (95), 89 (31), 65 (53).

Anal. Calcd for C₁₉H₁₉Cl₂N₃O₃S: C, 51.82; H, 4.35; N, 9.54; S, 7.28. Found: C, 52.02; H, 4.42; N, 9.52; S, 7.33.

5-Dichloromethyl-3-(4-methoxyphenyl)-1-tosylaminocarbonyl-2-pyrazoline (7e)

Yield: 1.10 g (97%); white needles; mp 217 °C (dec) (MeCN).

IR (Nujol): 3314, 1695, 1609, 1346, 1257, 1180, 1069, 832, 788, 733, 665 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.43 (s, 3 H), 3.44 (dd, J = 18.2, 11.3 Hz, 1 H), 3.58 (dd, J = 18.2, 5.7 Hz, 1 H), 3.86 (s, 3 H), 4.84 (ddd, J = 11.3, 5.7, 2.6 Hz, 1 H), 6.40 (d, J = 2.6 Hz, 1 H), 6.94 (d, J =8.9 Hz, 2 H), 7.32 (d, J = 8.4 Hz, 2 H), 7.65 (d, J = 8.9 Hz, 2 H), 7.98 (d, J = 8.4 Hz, 2 H), 8.62 (br s, 1 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.67 (CH₃), 35.55 (CH₂), 55.80 (CH₃), 63.35 (CH), 71.29 (CHCl₂), 114.59 (CH), 122.44 (C), 128.49 (CH), 128.73 (CH), 129.64 (CH), 136.55 (C), 144.84 (C), 148.53 (C=O), 154.81 (C=N), 162.37 (C).

MS: m/z (%) = 455 (0.3) [M]⁺, 457 (0.2) [M⁺+2], 258 (11), 260 (7), 197 (18), 175 (100), 155 (30), 160 (27), 91 (45), 65 (15).

Anal. Calcd for C₁₉H₁₉Cl₂N₃O₄S: C, 50.01; H, 4.20; N, 9.21; S, 7.03. Found: C, 50.04; H, 4.16; N, 9.18; S, 7.07.

5-Dichloromethyl-3-(4-nitrophenyl)-1-tosylaminocarbonyl-2-pyrazoline (7f)

Yield: 1.10 g (93%); yellow needles; mp 248 °C (dec) (MeCN).

IR (Nujol): 3329, 1709, 1596, 1586, 1517, 1350, 1167, 1087, 1069, 848, 665 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 2.39 (s, 3 H), 3.50 (dd, J = 18.5, 5.5 Hz, 1 H), 3.67 (dd, J = 18.5, 11.5 Hz, 1 H), 5.06 (ddd, J = 11.5, 5.5, 2.8 Hz, 1 H), 6.56 (d, J = 2.8 Hz, 1 H), 7.42 (d, J = 7.9 Hz, 2 H), 7.86 (d, J = 7.9 Hz, 2 H), 8.23 (d, J = 8.6 Hz, 2 H), 8.30 (d, J = 8.6 Hz, 2 H), 11.61 (br s, 1 H).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 21.02 (CH₂), 35.14 (CH₂), 63.98 (CH), 72.30 (CHCl₂), 123.72 (CH), 127.58 (CH), 128.36 (CH), 129.44 (CH), 136.24 (C), 136.86 (C), 144.02 (C), 148.25 (C), 148.96 (C=O), 152.66 (C=N).

MS: m/z (%) = 470 (0.12) [M]⁺, 398 (6), 334 (25), 273 (4), 197 (22), 190 (61), 155 (61), 144 (34), 91 (100), 65 (32).

Anal. Calcd for C₁₈H₁₆Cl₂N₄O₅S: C, 45.87; H, 3.42; N, 11.89; S, 6.80. Found: C, 45.78; H, 3.40; N, 11.97; S, 6.81.

5-Dichloromethyl-3-(4-biphenylyl)-1-tosylaminocarbonyl-2-pyrazoline (7g)

Yield: 1.23 g (98%); yellow powder; mp 238 °C (dec) (MeCN/DMF).

IR (Nujol): 3275, 1692, 1594, 1344, 1162, 1076, 896, 841, 788, 732, 702, 663 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 2.39 (s, 3 H), 3.46 (dd, J = 18.4, 5.4 Hz, 1 H), 3.65 (dd, J = 18.4, 11.3 Hz, 1 H), 5.00 (ddd, J = 11.3, 5.4, 2.4 Hz, 1 H), 6.55 (d, J = 2.4 Hz, 1 H), 7.34–7.51 (m, 5 H), 7.68–7.79 (m, 4 H), 7.87 (d, J = 8.2 Hz, 2 H), 8.04 (d, J = 8.3 Hz, 2 H), 11.42 (1 H, br s).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 21.04 (CH₃), 34.38 (CH₂), 63.43 (CH), 72.46 (CHCl₂), 125.58 (C), 126.76 (CH), 127.60 (CH), 127.88 (CH), 128.01 (CH), 129.00 (CH), 129.20 (CH), 129.42 (CH), 137.02 (C), 139.15 (C), 142.09 (C), 143.93 (C), 148.93 (C=O), 154.10 (C=N).

MS: m/z (%) = 501 (1) [M]⁺, 503 (0.8) [M⁺+2], 429 (9), 304 (24), 306 (16), 221 (100), 197 (12), 155 (19), 91 (36).

Anal. Calcd for C₂₄H₂₁Cl₂N₃O₃S: C, 57.37; H, 4.21; N, 8.36; S, 6.38. Found: C, 57.45; H, 4.22; N, 8.41; S, 6.34.

5-Dichloromethyl-3-(2-naphthyl)-1-tosylaminocarbonyl-2-pyrazoline (7h)

Yield: 0.99 g (83%); white powder; mp 129–131 °C (dec) (Et₂O).

IR (ATR): 3243, 1695, 1597, 1440, 1376, 1067, 756, 780, 659 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.49 (s, 3 H), 3.62 (dd, J = 11.4, 18.4 Hz, 1 H), 3.76 (dd, J = 5.7, 18.4 Hz, 1 H), 4.93 (ddd, J = 2.6, 5.7, 11.4 Hz, 1 H), 6.45 (d, J = 2.6 Hz, 1 H), 7.35 (d, J = 8.3 Hz, 2 H), 7.56 (m, 2 H), 7.91 (m, 4 H), 8.03 (d, J = 8.1 Hz, 3 H), 8.75 (s, 1 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 22.56 (CH₃), 35.95 (CH₂), 64.18 (CH), 71.96 (CH), 123.87 (CH), 127.96 (CH), 128.75 (CH), 129.26 (CH), 129.45 (CH), 129.71 (CH), 130.47 (CH), 133.72 (C), 135.40 (C), 136.86 (C), 145.83 (C), 155.92 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₂₀Cl₂N₃O₃S: 476.0597; found: 476.0595.

5-Dichloromethyl-3-(3,4-dichlorophenyl)-1-tosylaminocarbonyl-2-pyrazoline (7i)

Yield: 0.87 g (70%); white powder; mp 205–207 °C (dec) (Et₂O).

IR (ATR): 3382, 1741, 1672, 1527, 1446, 1311, 855, 824, 749, 733, 688 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 2.39 (s, 3 H), 3.46 (dd, J = 10.7, 18.2 Hz, 1 H), 3.57 (dd, J = 5.5, 18.2 Hz, 1 H), 4.90 (m, 1 H), 6.39 (d, J = 1.8 Hz, 1 H), 7.35 (d, J = 7.9 Hz, 2 H), 7.54 (q, J = 7.8 Hz, 2 H), 7.80 (s, 1 H), 7.89 (d, J = 8.1 Hz, 2 H), 8.69 (s, 1 H).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 22.41 (CH₃), 35.74 (CH₂), 64.86 (CH), 73.88 (CH), 126.75 (CH), 129.25 (CH), 129.45 (CH), 130.38 (C), 130.50 (CH), 131.87 (CH), 134.40 (C), 136.40 (C), 136.67 (C), 145.96 (C), 149.05 (C), 153.71 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₆Cl₄N₃O₃S: 493.9661; found: 493.9679.

3-(3-Bromophenyl)-5-dichloromethyl-1-tosylaminocarbonyl-2-pyrazoline (7j)

Yield: 1.01 g (80%); white powder; mp 209–210 °C (dec) (Et₂O).

IR (ATR): 3240, 1716, 1696, 1442, 1420, 1170, 1072, 767, 664 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.43 (s, 3 H), 3.46 (dd, J =11.5, 18.4 Hz, 1 H), 3.57 (dd, J = 5.8, 11.5 Hz, 1 H), 4.89 (ddd, J = 2.6, 5.8, 11.5 Hz, 1 H), 6.40 (d, J = 2.6 Hz, 1 H), 7.3 (m, 3 H), 7.57 (dd, J = 7.7, 0.9 Hz, 1 H), 7.63 (d, J = 7.7 Hz, 1 H), 7.86 (t, J = 1.7 Hz, 1 H), 7.98 (d, J = 8.3 Hz, 2 H), 8.80 (s, 1 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 22.60 (CH₃), 35.78 (CH₂), 64.25 (CH), 71.84 (CH), 123.95, 126.39 (CH), 129.24 (CH), 130.50 (CH), 131.32 (CH), 132.43 (C), 134.96 (CH), 136.70 (C), 145.90 (C), 149.75 (C), 154.49 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₇BrCl₂N₃O₃S: 503.9546; found: 503.9537.

Synthesis of 10; General Procedures

Method (a): A suspension of 7 (0.5 mmol) in triethylamine (10 mL) was heated to reflux for 4 h. Then, the solvent was removed in vacuo and the residue was washed with cold water (25 mL), leaving a solid that was collected by filtration, dried and crystallized from the appropriate solvent.

Method (b): Compound 7 (0.5 mmol) and triethylamine (10 mL) were placed in a sealed pressurized reaction vessel and heated at 130 °C for 2 h. After cooling, the solvent was removed in vacuo and the residue was washed with cold water (25 mL), leaving a solid that was collected by filtration, dried and crystallized from the appropriate solvent.

One-Pot Procedure; Method (c): Pyrazoline 5 (0.6 mmol), toluenesulfonyl isocyanate (0.72 mmol) and triethylamine (10 mL) were placed in a sealed pressurized reaction vessel and heated at 130 °C for 2 h. After cooling, the solvent was removed in vacuo and the residue was washed with cold water (25 mL), leaving a solid that was collected by filtration, dried and crystallized from the appropriate solvent.

2-Phenyl-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10a)

Yield: 88 mg (50%) (method A); 134 mg (63%) (method C); white needles; mp 237 °C (dec) (MeOH).

IR (Nujol): 3285, 1698, 1599, 1379, 1346, 1163, 1078, 895, 866, 848, 785, 673 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.44 (s, 3 H), 4.92 (s, 2 H), 6.58 (s, 1 H), 7.36–7.42 (m, 5 H), 7.85 (d, J = 6.7 Hz, 2 H), 8.01 (d, J = 7.9 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.80 (CH₃), 44.53 (CH₂), 99.69 (CH), 126.64 (CH), 128.30 (CH), 128.90 (CH), 129.73 (CH), 130.21 (CH), 131.45 (C), 134.46 (C), 140.90 (C), 144.99 (C=O), 146.23 (C), 160.96 (C=N).

MS: m/z (%) = 353 (33) [M]⁺, 289 (37) [M⁺– SO₂], 260 (14), 245 (10), 199 (9), 155 (19), 128 (100), 115 (29), 91 (98), 65 (34).

Anal. Calcd for C₁₈H₁₅N₃O₃S: C, 61.18; H, 4.28; N, 11.89; S, 9.07. Found: C, 61.28; H, 4.30; N, 11.95; S, 9.10.

2-(4-Chlorophenyl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10b)

Yield: 122 mg (63%) (method b); 174 mg (63%) (method c); white needles; mp 263 °C (dec) (MeOH/CHCl₃).

IR (Nujol): 1790, 1598, 1584, 1565, 1434, 1318, 1169, 1110, 818, 731 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.45 (s, 3 H), 4.93 (s, 2 H), 6.56 (s, 1 H), 7.39 (br s, 4 H), 7.79 (d, J = 7.1 Hz, 2 H), 8.02 (d, J = 7.3 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.83 (CH₃), 44.51 (CH₂), 99.58 (CH), 127.89 (CH), 128.33 (CH), 129.18 (CH), 129.94 (C), 130.24 (CH), 134.28 (C), 135.75 (C), 141.06 (C), 144.90 (C=O), 146.33 (C), 159.82 (C=N).

MS: m/z (%) = 387 (36) [M]⁺, 389 (14) [M⁺+ 2], 323 (30) [M⁺– SO₂], 232 (4), 162 (49), 155 (22), 91 (100), 65 (29).

Anal. Calcd for C₁₈H₁₄ClN₃O₃S: C, 55.74; H, 3.64; N, 10.83; S, 8.27. Found: C, 55.68; H, 3.66; N, 10.78; S, 8.30.

2-(4-Bromophenyl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10c)

Yield: 82 mg (38%) (method b); 147 mg (57%) (method c); white powder; mp 260 °C (dec) (MeOH/Me₂CO).

IR (Nujol): 1782, 1599, 1320, 1173, 1105, 954, 813, 799, 733, 684 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.44 (s, 3 H), 4.91 (d, J =1.0 Hz, 2 H), 6.53 (t, J = 1.0 Hz, 1 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.54 (d, J = 8.5 Hz, 2 H), 7.71 (d, J = 8.5 Hz, 2 H), 8.01 (d, J = 8.2 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.75 (CH₃), 44.48 (CH₂), 99.47 (CH), 124.08 (C), 128.22 (CH), 128.46 (CH), 130.24 (CH), 130.67 (C), 132.21 (CH), 134.73 (C), 141.23 (C), 144.88 (C=O), 146.26 (C), 159.98 (C=N).

MS: m/z (%) = 431 (24) [M]⁺, 433 (23) [M⁺+ 2], 367 (18) [M⁺ – SO₂], 277 (2), 206 (25), 169 (19), 155 (25), 127 (26), 91 (100), 65 (30).

Anal. Calcd for C₁₈H₁₄BrN₃O₃S: C, 50.01; H, 3.26; N, 9.72; S, 7.42. Found: C, 50.10; H, 3.30; N, 9.69; S, 7.35.

2-(p-Tolyl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10d)

Yield: 121 mg (65%) (method a); 154 mg (70%) (method c); white needles; mp 241 °C (dec) (Me₂SO).

IR (Nujol): 1776, 1589, 1330, 1163, 1107, 951, 821, 800, 734, 686, 665 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.37 (s, 3 H), 2.43 (s, 3 H), 4.88 (d, J = 1.0 Hz, 2 H), 6.53 (t, J = 1.0 Hz, 1 H), 7.21 (d, J = 8.0 Hz, 2 H), 7.35 (d, J = 8.2 Hz, 2 H), 7.73 (d, J = 8.0 Hz, 2 H), 7.99 (d, J = 8.2 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.42 (CH₃), 21.77 (CH₃), 44.51 (CH₂), 99.53 (CH), 126.53 (CH), 128.26 (CH), 128.64 (CH), 129.59 (C), 130.17 (CH), 134.40 (C), 139.87 (C), 140.84 (C), 145.01 (C=O), 146.15 (C), 161.03 (C=N).

MS: m/z (%) = 367 (51) [M]⁺, 303 (47) [M⁺ – SO₂], 213 (27), 170 (28), 155 (35), 141 (100), 128 (37), 115 (50), 91 (70), 65 (42).

Anal. Calcd for C₁₉H₁₇N₃O₃S: C, 62.11; H, 4.66; N, 11.44; S, 8.73. Found: C, 62.20; H, 4.69; N, 11.40; S, 8.64.

2-(4-Methoxyphenyl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10e)

Yield: 88 mg (46%) (method b); 176 mg (77%) (method c); white needles; mp 185 °C (dec) (MeOH).

IR (Nujol): 1787, 1756, 1616, 1570, 1529, 1332, 1316, 1284, 1251, 1162, 1104, 1034, 817, 731, 668 cm^–1.

¹H NMR (CDCl₃, 300 MHz): δ = 2.42 (s, 3 H), 3.83 (s, 3 H), 4.88 (d, J = 1.2 Hz, 2 H), 6.50 (t, J = 1.2 HZ, 1 H), 6.92 (d, J = 8.8 Hz, 2 H), 7.35 (d, J = 8.3 HZ, 2 H), 7.77 (d, J = 8.8 Hz, 2 H), 7.99 (d, J = 8.3 Hz, 2 H).

¹³C NMR (CDCl₃, 75.4 MHz): δ = 21.77 (CH₃), 44.50 (CH₂), 55.39 (CH₃), 99.30 (CH), 114.25 (CH), 123.98 (C), 128.00 (CH), 128.21 (CH), 130.15 (CH), 134.05 (C), 140.87 (C), 145.02 (C=O), 146.14 (C), 160.75 (C=N).

MS: m/z (%) = 383 (39) [M]⁺, 319 (7) [M⁺ – SO₂], 228 (12), 172 (27), 158 (100), 143 (28), 115 (39), 91 (65), 65 (22).

Anal. Calcd for C₁₉H₁₇N₃O₄S: C, 59.52; H, 4.47; N, 10.96; S, 8.36. Found: C, 59.44; H, 4.35; N, 10.91; S, 8.43.

2-(4-Nitrophenyl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10f)

Yield: 108 mg (55%) (method b); 211 mg (88%) (method c); white powder; mp 288 °C (dec) (Me₂SO).

IR (Nujol): 3121, 1784, 1576, 1517, 1340, 1310, 1164, 1105, 954, 731, 704, 685, 666 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 2.43 (s, 3 H), 5.15 (s, 2 H), 7.04 (s, 1 H), 7.49 (d, J = 8.2 Hz, 2 H), 7.98 (d, J = 8.2 Hz, 2 H), 8.14 (d, J = 8.4 Hz, 2 H), 8.28 (d, J = 8.4 Hz, 2 H).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 20.46 (CH₃), 44.60 (CH₂), 99.97 (CH), 123.44 (CH), 126.85 (CH), 127.39 (CH), 129.43 (CH), 134.00 (C), 137.23 (C), 142.92 (C), 144.24 (C), 145.20 (C=O), 147.60 (C), 157.13 (C=N).

MS: m/z (%) = 398 (5) [M]⁺, 334 (23) [M⁺ – SO₂], 243 (3), 173 (7), 155 (26), 114 (9), 91 (100), 65 (30).

Anal. Calcd for C₁₈H₁₄N₄O₅S: C, 54.27; H, 3.54; N, 14.06; S, 8.05. Found: C, 54.18; H, 3.51; N, 14.16; S, 8.08.

2-(4-Biphenylyl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10g)

Yield: 129 mg (60%) (method b); 176 mg (68%) (method c); white powder; mp 276 °C (dec) (MeOH/Me₂CO).

IR (Nujol): 1788, 1774, 1594, 1326, 1175, 1106, 950, 801, 769, 727, 669 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.45 (s, 3 H), 4.94 (s, 2 H), 6.62 (s, 1 H), 7.35–7.39 (m, 3 H), 7.45 (t, J = 7.5 Hz, 2 H), 7.61 (d, J = 7.5 Hz, 2 H), 7.65 (d, J = 8.2 Hz, 2 H), 7.93 (d, J = 8.2 Hz, 2 H), 8.03 (d, J = 8.3 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.75 (CH₃), 44.51 (CH₂), 99.63 (CH), 127.16 (CH), 127.17 (CH), 127.63 (CH), 127.82 (C), 128.45 (CH), 128.97 (CH), 130.22 (CH), 130.58 (C), 134.78 (C), 140.55 (C), 141.04 (C), 142.67 (C), 144.97 (C=O), 146.19 (C), 160.79 (C=N).

MS: m/z (%) = 429 (71) [M]⁺, 365 (18) [M⁺ – SO₂], 275 (26), 218 (25), 204 (97), 189 (22), 155 (15), 91 (100), 65 (30).

Anal. Calcd for C₂₄H₁₉N₃O₃S: C, 67.12; H, 4.46; N, 9.78; S, 7.47. Found: C, 67.03; H, 4.44; N, 9.85; S, 7.50.

2-(Naphthalen-2-yl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10h)

Yield: 157 mg (78%) (method a); 198 mg (82%) (method c); white powder; mp 250–251 °C (dec) (Et₂O).

IR (ATR): 1722, 1586, 1432, 1374, 1343, 1170, 1105, 780, 686, 661 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 2.40 (s, 3 H), 5.21 (s, 2 H), 7.11 (s, 1 H,), 7.49 (d, J = 8.4 Hz, 2 H), 7.54 (d, J = 8.4 Hz, 2 H), 7.98 (m, 5 H), 8.49 (s, 1 H).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 20.66 (CH₃), 44.77 (CH₂), 99.53 (CH), 125.32 (CH), 126.21 (CH), 126.38 (CH), 127.22 (CH), 127.53 (CH), 127.90 (CH), 128.10 (CH), 128.62 (CH), 129.59 (C), 132.63 (CH), 133.00 (C), 134.12 (C), 142.68 (C), 144.57 (C), 145.29 (C), 159.47 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₈N₃O₃S: 404.1063; found: 404.1051.

2-(3,4-Dichlorophenyl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10i)

Yield: 169 mg (80%) (method b); 215 mg (85%) (method c); white powder; mp 252–253 °C (dec) (Et₂O).

IR (ATR): 1787, 1595, 1427, 1371, 1346, 1299, 1164, 1105, 1027, 814, 664 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 2.40 (s, 3 H), 5.17 (s, 2 H), 7.08 (s, 1 H), 7.48 (d, J = 4.4 Hz, 2 H), 7.71 (d, J = 6.6 Hz, 1 H), 7.88 (d, J = 6.6 Hz, 1 H), 7.97 (d, J = 4.4 Hz, 2 H), 8.13 (s, 1 H).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 22.48 (CH₃), 46.65 (CH₂), 101.34 (CH), 127.55 (CH), 129.18 (C), 124.41 (CH), 131.35 (CH), 132.59 (CH), 133.22 (CH), 133.34 (C), 135.43 (C), 144.81 (C), 146.22 (C), 147.15 (C), 158.56 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₄Cl₂N₃O₃S: 422.0127; found: 422.0146.

2-(3-Bromophenyl)-5-tosyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (10j)

Yield: 143 mg (65%) (method a); 212 mg (82%) (method c); white powder; mp 202–203 °C (dec) (Et₂O).

IR (ATR): 1798, 1590, 1364, 1309, 1160, 1170, 782, 727, 686, 661 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 2.41 (s, 3 H), 5.18 (s, 2 H), 7.07 (s, 1 H), 7 (d, J = 8.2 Hz, 2 H), 7.63 (dd, J = 7.0, 14.1 Hz, 2 H), 7.90 (d, J = 7.0 Hz, 1 H), 7.97 (d, J = 8.1 Hz, 2 H), 8.07 (s, 1 H).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 22.49 (CH₃), 46.89 (CH₂), 101.24 (CH), 123.66 (C), 126.52 (CH), 129.41 (CH), 129.93 (CH), 131.35 (CH), 132.53 (CH), 133.54 (CH), 135.09 (C), 135.45 (C), 144.69 (C), 146.30 (C), 147.13 (C), 159.55 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₅BrN₃O₃S: 432.0012; found: 431.9999.

Synthesis of 11; General Procedure

To a solution of compound 5 (3 mmol) in anhydrous tetrahydrofuran (15 mL), the corresponding isocyanate (3.6 mmol) was added dropwise. The reaction mixture was stirred for 4 h at r.t. under a nitrogen atmosphere. Then, the solvent was evaporated under reduced pressure, obtaining a solid residue that was crystallized from the appropriate solvent. Product 11b was prepared in EtOH instead of THF.

N-Benzyl-5-dichloromethyl-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide (11a)

Yield: 0.56 g (50%); off-white powder; mp 121–122 °C (dec) (EtOAc/ pet ether).

IR (KBr): 3290, 3207, 6064, 2974, 1946, 1890, 1659, 1571, 1554, 1454, 1366, 1299, 1217, 111, 1080, 1028, 874, 818, 780, 745, 695 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.40 (s, 3 H), 3.47 (dd, J = 11.4, 18.2 Hz, 1 H), 3.59 (dd, J = 6.0, 18.2 Hz, 1 H), 4.39 (t, J = 6.0 Hz, 2 H), 4.99 (ddd, J = 2.4, 6, 11.4 Hz, 1 H), 6.43 (t, J = 6 Hz, 1 H), 6.63 (d, J = 2.4 Hz, 1 H), 7.23 (d, J = 8 Hz, 2 H), 7.30 (m, 1 H), 7.37 (m, 4 H), 7.60 (d, J = 8 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 22.39 (CH₃), 35.52 (CH₂), 44.84 (CH₂), 64.55 (CH), 73.46 (CH), 127.33 (CH), 128.26 (CH), 128.46 (CH), 128.79 (C), 129.55 (CH), 130.33 (CH), 139.85 (C), 141.60 (C), 153.09 (C), 155.47 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₂₀Cl₂N₃O: 376.0978; found: 376.0972.

N-Cyclohexyl-5-dichloromethyl-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide (11b)

Yield: 0.48 g (43%); white powder; mp 158–160 °C (dec) (EtOAc/pet ether).

IR (KBr): 3316, 2931, 2849, 1815, 650, 1595, 1528, 1514, 1449, 1415, 1392, 1326, 1253, 1160, 1134, 1079, 938, 871, 818, 752, 704, 646 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 1.20 (m, 3 H), 1.37 (m, 2 H), 1.63 (d, J = 12 Hz, 1 H), 1.74 (m, 2 H), 1.99 (t, J = 11.6 Hz, 2 H), 2.40 (s, 3 H), 3.45 (dd, J = 11.6, 18 Hz, 1 H), 3.65 (dd, J = 6, 18 Hz, 1 H), 3.68 (m, 1 H), 4.94 (m, 1 H), 5.91 (d, J = 8 Hz, 1 H), 6.55 (d, J = 2 Hz, 1 H), 7.23 (d, J = 8 Hz, 2 H), 7.60 (d, J = 8 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 22.45 (CH₃), 25.93 (CH₂), 26.47 (CH₂), 34.52 (CH₂), 34.73 (CH₂), 35.48 (CH₂), 49.87 (CH), 64.50 (CH), 73.62 (CH), 127.28 (CH), 128.92 (C), 130.30 (CH), 141.46 (C), 152.64 (C), 154.81 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₂₄Cl₂N₃O: 368.1291; found: 368.1297.

5-Dichloromethyl-N-(2-ethylhexyl)-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide (11c)

Yield: 0.61 g (51%); pale-yellow oil (silica gel column chromatography; pet ether/EtOAc).

IR (KBr): 3604, 3437, 2730, 2019, 1725, 1681, 1528, 1513, 1466, 1376, 1319, 1296, 1251, 1166, 1136, 873, 813, 729, 720, 634 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 0.90 (m, 6 H), 1.32 (m, 9 H), 2.39 (s, 3 H), 3.25 (m, 2 H), 3.44 (dd, J = 11.6, 18.2 Hz, 1 H), 3.55 (dd, J = 6.2, 18.2 Hz, 1 H), 4.94 (ddd, J = 2.6, 6.2, 11.6 Hz, 1 H), 6.03 (d, J = 5.6, 1 H), 6.58 (d, J = 2.6 Hz, 1 H), 7.22 (d, J = 8 Hz, 2 H), 7.59 (d, J = 8 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 11.72 (CH₃), 15.04 (CH₃), 22.69 (CH₃), 23.83 (CH₂), 24.98 (CH₂), 29.82 (CH₂), 31.61 (CH₂), 35.68 (CH₂), 40.78 (CH), 44.10 (CH2), 64.54 (CH), 73.56 (CH), 127.23 (CH), 128.97 (C), 130.29 (CH), 1141.42 (C), 152.58 (C), 155.64 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₃₀Cl₂N₃O: 398.1760; found: 398.1775.

5-Dichloromethyl-N-phenyl-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide­ (11d)

Yield: 0.80 g (74%); off-white powder; mp 149–150 °C (dec) (EtOAc/ pet ether).

IR (KBr): 3317, 2989, 1938, 1891, 1665, 1594, 1533, 1501, 1448, 1391, 1329, 1313, 1234, 1144, 1112, 1029, 931, 868, 819, 760, 748, 701, 692, 643 cm^–1.

¹H NMR (CDCl₃, 300 MHz): δ = 2.42 (s, 3 H), 3.57 (dd, J = 11.4, 18 Hz, 1 H), 3.65 (dd, J = 6.1, 18 Hz, 1 H), 5.04 (ddd, J = 2.5, 6.1, 11.4 Hz, 1 H), 6.62 (d, J = 2.5 Hz, 1 H), 7.09 (t, J = 7.6 Hz, 1 H), 7.27 (t, J = 7.6 Hz, 2 H), 7.34 (t, J = 7.6 Hz, 2 H), 7.53 (d, J = 8.6 Hz, 2 H), 7.67 (d, J = 8.6 Hz, 2 H), 8.20 (s, 1 H).

¹³C NMR (CDCl₃, 75.4 MHz): δ = 22.54 (CH₃), 35.89 (CH₂), 64.44 (CH), 73.26 (CH), 120.30 (CH), 124.41 (CH), 127.58 (CH), 128.66 (C), 130.02 (CH), 130.54 (CH), 139.01 (C), 142.08 (C), 152.68 (C), 153.78 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₈Cl₂N₃O: 362.0821; found: 362.0826.

5-Dichloromethyl-N-p-tolyl-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide­ (11e)

Yield: 0.79 g (70%); off-white powder; mp 155–156 °C (dec) (EtOAc/ pet ether).

IR (KBr): 3387, 2919, 1913, 1667, 1592, 1532, 1416, 1387, 1315, 1233, 1166, 1104, 1028, 933, 868, 812, 758, 748, 734, 698, 646 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.33 (s, 3 H), 2.42 (s, 3 H), 3.52 (dd, J = 11.4, 18.4 Hz, 1 H), 3.63 (dd, J = 6, 18.4 Hz, 1 H), 5.03 (ddd, J = 2.2, 6, 11.2 Hz, 1 H), 6.61 (d, J = 2.2 Hz, 1 H), 7.14 (d, J = 8 Hz, 2 H), 7.26 (d, J = 8 Hz, 2 H), 7.40 (d, J = 8 Hz, 2 H), 7.66 (d, J = 8 Hz, 2 H), 7.95 (s, 1 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 21.69 (CH₃), 22.43 (CH₃), 35.75 (CH₂), 64.33 (CH), 73.20 (CH), 120.37 (CH), 127.45 (CH), 128.57 (C), 130.41 (CH), 133.89 (C), 136.24 (C), 141.92 (C), 152.71 (C), 153.56 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₂₀Cl₂N₃O: 376.0978; found: 376.0980.

5-Dichloromethyl-N-(4-chlorophenyl)-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide (11f)

Yield: 0.83 g (70%); white needles; mp 174–175 °C (dec) (EtOAc/pet ether).

IR (KBr): 3396, 3066, 1907, 1669, 1590, 1525, 1494, 1416, 1310, 1230, 1166, 1136, 1090, 1010, 935, 846, 757, 729, 673 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.43 (s, 3 H), 3.54 (dd, J = 11.6, 18.4 Hz, 1 H), 3.65 (dd, J = 5.6, 18.4 Hz, 1 H), 5.04 (m, 1 H), 6.60 (br s, 1 H), 7.29 (m, 4 H), 7.48 (d, J = 8.4 Hz, 4 H), 7.66 (d, J = 7.6 Hz, 2 H), 8.02 (s, 1 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 22.45 (CH₃), 35.84 (CH₂), 64.27 (CH), 72.99 (CH), 121.33 (CH), 127.50 (CH), 128.38 (C), 129.18 (C), 129.88 (CH), 130.46 (CH), 137.52 (C), 142.13 (C), 152.36 (C), 153.99 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₇Cl₃N₃O: 396.0432; found: 396.0434.

5-Dichloromethyl-N-(4-fluorophenyl)-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide (11g)

Yield: 0.82 g (72%); off-white needles; mp 165 °C (dec) (Me₂CHOH).

IR (KBr): 3384, 3295, 3029, 1882, 1667, 1636, 1610, 1593, 1510, 1418, 13866, 1525, 1313, 1210, 1096, 849, 832, 767, 734, 703, 607 cm^–1.

¹H NMR (CDCl₃, 300 MHz): δ = 2.42 (s, 3 H), 3.54 (dd, J = 11.4, 18.1 Hz, 1 H), 3.64 (dd, J = 6.3, 18.1 Hz, 1 H), 5.03 (m, 1 H), 6.59 (d, J = 1.8 Hz, 1 H), 7.03 (t, J = 8.4 Hz, 2 H), 7.27 (d, J = 6.6 Hz, 2 H), 7.47 (dd, J = 4.5, 8.7 Hz, 2 H), 7.66 (d, J = 7.8 Hz, 2 H), 7.96 (s, 1 H).

¹³C NMR (CDCl₃, 75.4 MHz): δ = 22.54 (CH₃), 35.92 (CH₂), 64.42 (CH), 73.17 (CH), 116.62 (d, J = 22.4 Hz, CH), 122.13 (d, J = 7.8 Hz, CH), 127.57 (CH), 128.57 (C), 130.55 (CH), 134.92 (d, J = 2.3 Hz, C), 142.16 (C), 152.77 (C), 153.94 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₇Cl₂FN₃O: 380.0727; found: 380.0735.

N-(4-Bromophenyl)-5-(dichloromethyl)-4,5-dihydro-3-p-tolylpyrazole-1-carboxamide (11h)

Yield: 0.94 g (71%); white needles; mp 189–191 °C (dec) (EtOAc/pet ether).

IR (KBr): 3398, 1894, 1673, 1587, 1526, 1513, 1488, 1406, 1324, 1312, 1231, 1071, 1008, 843, 814, 805, 756, 729, 655 cm^–1.

¹H NMR (CDCl₃, 300 MHz): δ = 2.42 (s, 3 H), 3.54 (dd, J = 11.2, 18.3 Hz, 1 H), 3.65 (dd, J = 6.3, 18.3 Hz, 1 H), 5.02 (ddd, J = 2.6, 6.3, 11.2 Hz, 1 H), 6.58 (d, J = 2.6 Hz, 1 H), 7.27 (d, J = 8.0 Hz, 2 H), 7.43 (m, 4 H), 7.66 (d, J = 8.0 Hz, 2 H), 8.00 (s, 1 H).

¹³C NMR (CDCl₃, 75.4 MHz): δ = 22.55 (CH₃), 35.95 (CH₂), 64.36 (CH), 73.07 (CH), 116.82 (C), 121.75 (CH), 127.61 (CH), 128.48 (C), 130.56 (CH), 132.93 (CH), 138.15 (C), 142.25 (C), 152.41 (C), 154.12 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₇BrCl₂N₃O: 439.9927; found: 439.9942.

5-Dichloromethyl-4,5-dihydro-N-p-tolyl-3-phenylpyrazole-1-carboxamide (11i)

Yield: 0.69 g (63%); white needles; mp 196 °C (dec) (EtOAc/pet ether).

IR (KBr): 3307, 1659, 1593, 1539, 1442, 1403, 1250, 1172, 933, 783, 764, 738, 689 cm^–1.

¹H NMR (CDCl₃, 300 MHz): δ = 2.34 (s, 3 H), 3.52 (dd, J = 11.3, 18.4 Hz, 1 H), 3.64 (dd, J = 6.3, 18.4 Hz, 1 H), 5.03 (ddd, J = 2.4, 6.3, 11.3 Hz, 1 H), 6.12 (d, J = 2.4 Hz, 2 H), 6.89 (d, J = 7.4 Hz, 1 H), 7.20 (t, J = 7.8 Hz, 2 H), 7.28 (d, J = 8.1 Hz, 1 H), 7.37 (s, 1 H), 7.45 (m, 3 H), 7.76 (dd, J = 3.4, 6.8 Hz, 2 H), 7.95 (s, 1 H).

¹³C NMR (CDCl₃, 75.4 MHz): δ = 22.52 (CH₃), 35.81 (CH₂), 64.57 (CH₂), 73.20 (CH), 117.38 (CH), 120.93 (CH), 125.29 (CH), 127.60 (CH), 129.82 (CH), 131.45 (C), 131.61 (CH), 138.85 (C), 139.94 (C), 152.66 (C), 153.61 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₈Cl₂N₃O: 362.0821; found: 362.0821.

5-Dichloromethyl-4,5-dihydro-3-(naphthalen-3-yl)-N-phenylpyrazole-1-carboxamide (11j)

Yield: 0.73 g (61%); off-white powder; mp 146–146 °C (dec) (EtOAc/ pet ether).

IR (KBr): 3382, 1741, 1672, 1595, 1527, 1466, 1323, 825, 749, 688 cm^–1.

¹H NMR (CDCl₃, 300 MHz): δ = 3.65 (dd, J = 11.2, 18.1 Hz, 1 H), 3.78 (dd, J = 6.0, 18.1 Hz, 1 H), 5.09 (ddd, J = 2.4, 6.0, 11.2 Hz, 1 H), 7.08 (t, J = 7.4 Hz, 1 H), 7.34 (t, J = 8.1 Hz, 2 H), 7.54 (m, 4 H), 7.88 (m, 3 H), 8.02 (t, J = 7.4 Hz, 3 H).

¹³C NMR (CDCl₃, 75.4 MHz): δ = 35.80 (CH₂), 64.80 (CH), 73.31 (CH), 120.36 (CH), 124.01 (CH), 124.51 (CH), 127.94 (CH), 128.34 (CH), 128.49 (CH), 128.82 (CH), 128.97 (C), 129.48 (CH), 129.62 (CH), 130.04 (CH), 133.98 (C), 135.24 (C), 138.94 (C), 152.59 (C), 153.70 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₁₈Cl₂N₃O: 398.0821; found: 398.0834.

3-(3-Bromophenyl)-5-dichloromethyl-4,5-dihydro-N-phenylpyrazole-1-carboxamide (11k)

Yield: 0.77 g (61%); off-white powder; mp 138–140 °C (dec) (EtOAc/ pet ether).

IR (KBr): 3308, 1597, 1663, 1530, 1446, 1315, 1233, 873, 764, 750, 688 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 3.59 (dd, J = 11.3, 18.1 Hz, 1 H), 3.64 (dd, J = 5.9, 18.1 Hz, 1 H), 5.01 (m, 1 H), 6.62 (d, J = 1.8 Hz, 2 H), 7.10 (t, J = 7.4 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 2 H), 7.59 (d, J = 6.9 Hz, 1 H), 7.37 (d, J = 7.6 Hz, 1 H), 7.95 (d, J = 9.8 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 35.56 (CH₂), 64.60 (CH), 72.92 (CH), 120.31 (CH), 123.95 (C), 124.52 (CH), 126.05 (CH), 129.64 (CH), 130.29 (CH), 131.24 (CH), 133.39 (C), 134.33 (CH), 138.63 (C), 152.16 (C), 152.36 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₅BrCl₂N₃O: 425.977; found: 425.980.

Synthesis of 12; General Procedure

A mixture of 11 (3 mmol), dioxane (5 mL), and DBU (9 mmol) was stirred for 3 h at 100 °C. The solvent was then evaporated under reduced pressure, leaving a solid residue that was crystallized from the appropriate solvent.

5-Benzyl-2-p-tolyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12a)

Yield: 0.36 g (40%); white powder; mp 202–203 °C (dec) (Me₂CHOH/H₂O).

IR (KBr): 3476, 3031, 1948, 1746, 1585, 1495, 1467, 1445, 1406, 1314, 1298, 1246, 1077, 986, 930, 826, 806, 746, 699, 657, 623 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 2.37 (s, 3 H), 4.24 (br s, 2 H), 4.69 (br s, 2 H), 7.22 (d, J = 6.8 Hz, 2 H), 7.33 (m, 5 H), 7.79 (d, J = 6.8 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 22.20 (CH₃), 44.16 (CH₂), 48.78 (CH₂), 99.08 (CH), 127.12 (CH), 129.12 (CH), 129.91 (CH), 130.27 (CH), 130.43 (C), 136.40 (C), 139.76 (C), 142.66 (C), 150.76 (C), 159.69 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₈N₃O: 304.1444; found: 304.1443.

5-Cyclohexyl-2-p-tolyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12b)

Yield: 0.62 g (70%); beige powder; mp 201–203 °C (dec) (Me₂CHOH/H₂O).

IR (KBr): 3326, 2930, 2851, 1753, 1626, 1575, 1445, 1317, 1298, 1229, 1088, 892, 804, 741, 641 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 1.50 (t, J = 9.2 Hz, 2 H), 1.63 (m, 2 H), 1.76 (d, J = 9.6 Hz, 2 H), 1.79 (s, 1 H), 2.32 (s, 3 H), 3.77 (s, 1 H), 4.52 (s, 2 H), 5.56 (d, J = 7.2 Hz, 1 H), 6.83 (s, 1 H), 7.24 (d, J = 7.6 Hz, 2 H), 7.77 (d, J = 7.6 Hz, 2 H).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 22.19 (CH₃), 25.78 (CH₂), 26.31 (CH₂), 26.66 (CH₂), 31.43 (CH₂), 34.67 (CH₂), 48.83 (CH₂), 53.54 (CH), 99.23 (CH), 127.09 (CH), 130.71 (CH), 131.08 (C), 139.48 (C), 144.76 (C), 149.91 (C), 158.49 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₂₂N₃O: 296.1757; found: 296.1757.

5-(2-Ethylhexyl)-2-p-tolyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12c)

Yield: 0.52 g (53%); off-white powder; mp 106–107 °C (dec) (Me₂CHOH/H₂O).

IR (KBr): 3399, 2960, 2927, 1748, 1674, 1633, 1586, 1529, 1466, 1445, 1406, 1315, 1297, 1236, 1117, 1100, 108, 804, 739, 665 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 1.25 (m, 13 H), 2.38 (s, 3 H), 3.09 (d, J = 4 Hz, 2 H), 3.43 (t, J = 6.8 Hz, 2 H), 4.38 (s, 2 H), 6.52 (s, 1 H), 7.24 (d, J = 8 Hz, 2 H), 7.79 (d, J = 8 Hz, 2 H).

¹³C NMR (CDCl₃, 100.8 MHz): δ = 11.33 (CH₃), 11.76 (CH₃), 14.96 (CH₃), 22.22 (CH), 23.91 (CH₂), 24.48 (CH₂), 25.00 (CH₂), 29.44 (CH₂), 29.78 (CH₂), 31.23 (CH₂), 31.81 (CH₂), 38.88 (CH), 40.61 (CH), 44.33 (CH₂), 45.20 (CH₂), 48.61 (CH₂), 98.92 (CH), 127.09 (CH), 130.28 (CH), 130.43 (C), 139.73 (C), 142.53 (C), 151.04 (C), 159.50 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₂₈N₃O: 326.2227; found: 326.2235.

5-Phenyl-2-p-tolyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12d)

Yield: 0.61 g (70%); white powder; mp 260–261 °C (dec) (Me₂CHOH/H₂O).

IR (KBr): 3063, 1932, 1742, 1599, 1591, 1505, 1459, 1443, 1386, 1324, 1298, 1274, 1173, 1113, 1082, 1065, 953, 856, 836, 812, 745, 686, 656 cm^–1.

¹H NMR (DMSO-d ₆, 300 MHz): δ = 2.32 (s, 3 H), 5.09 (s, 2 H), 6.94 (s, 1 H), 7.19 (m, 1 H), 7.20 (d, J = 9.8 Hz, 2 H), 7.44 (t, J = 9.8 Hz, 2 H), 7.73 (d, J = 10.6 Hz, 2 H), 7.81 (d, J = 10.6 Hz, 2 H).

¹³C NMR (DMSO-d ₆, 75.4 MHz): δ = 22.35 (CH₃), 46.19 (CH₂), 99.65 (CH), 120.44 (CH), 125.95 (CH), 127.36 (CH), 130.59 (C), 130.91 (CH), 139.95 (C), 143.86 (C), 148.77 (C), 159.44 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₆N₃O: 290.1288; found: 290.1293.

2,5-Di-p-tolyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12e)

Yield: 0.68 g (75%); off-white powder; mp 230–231 °C (dec) (Me₂CHOH/H₂O).

IR (KBr): 3304, 2916, 1894, 1748, 1640, 1594, 1564, 1516, 1442, 1384, 1325, 1297, 1239, 1168, 1065, 953, 860, 813, 731, 627 cm^–1.

¹H NMR (DMF-d ₇, 400 MHz, 100 °C): δ = 2.37 (s, 3 H), 2.97 (3 H, s), 5.11 (s, 2 H), 6.84 (s, 1 H), 7.29 (d, J = 2.0 Hz, 2 H), 7.31 (d, J = 2.0 Hz, 2 H), 7.55 (d, J = 8.2 Hz, 2 H), 7.87 (d, J = 8.2 Hz, 2 H).

¹³C NMR (DMF-d ₇, 100.8 MHz, 100 °C): δ = 20.82 (CH₃), 21.30 (CH₃), 45.98 (CH₂), 98.94 (CH), 120.67 (CH), 127.08 (CH), 130.29 (CH), 130.49 (C), 131.21 (CH), 135.34 (C), 137.47 (C), 139.60 (C), 143.50 (C), 148.65 (C), 159.63 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₈N₃O: 304.1444; found: 304.1453.

5-(4-Chlorophenyl)-2-p-tolyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12f)

Yield: 0.81 g (83%); white needles; mp 298–299 °C (dec) (Me₂NCHO).

IR (KBr): 3296, 1914, 1744, 1633, 1590, 1561, 1496, 1443, 1394, 1328, 1299, 1288, 1098, 954, 859, 823, 801, 732, 629 cm^–1.

¹H NMR (DMF-d ₇, 400 MHz, 110 °C): δ = 2.52 (s, 3 H), 5.27 (s, 2 H), 6.96 (s, 1 H), 7.42 (d, J = 7.6 Hz, 2 H), 7.63 (d, J = 8.8 Hz, 2 H), 7.97 (d, J = 8.8 Hz, 2 H), 7.98 (d, J = 7.6 Hz, 2 H).

¹³C NMR (DMF-d ₇, 100.8 MHz): δ = 21.35 (CH₃), 46.07 (CH₂), 99.39 (CH), 122.15 (CH), 127.25 (CH), 130.06 (CH), 130.38 (CH), 131.30 (C), 139.11 (C), 139.86 (C), 143.59 (C), 148.78 (C), 160.14 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₅ClN₃O: 324.0898; found: 324.0892.

5-(4-Fluorophenyl)-2-p-tolyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12g)

Yield: 0.57 g (62%); white needles; mp 300 °C (dec) (Me₂NCHO).

IR (KBr): 3150, 2926, 1870, 1743, 1581, 1564, 1512, 1442, 1398, 1327, 1299, 1230, 1174, 1116, 1066, 954, 865, 823, 797, 732, 610 cm^–1.

¹H NMR (DMF-d ₇, 400 MHz, 110 °C): δ = 2.38 (m, 3 H), 5.12 (s, 2 H), 6.82 (s, 1 H), 7.26 (m, 4 H), 7.88 (m, 4 H).

¹³C NMR (DMF-d ₇, 100.8 MHz): δ = 26.48 (CH₃), 51.50 (CH₂), 104.26 (CH), 121.80 (d, J = 22.9 Hz, CH), 128.2 (d, J = 8.1 Hz, CH), 132.34 (CH), 135.50 (CH), 136.43 (C), 141.54 (C), 144.89 (C), 148.75 (C), 154.01 (C), 164.79 (C), 165.07 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₅FN₃O: 308.1194; found: 308.1196.

5-(4-Bromophenyl)-2-p-tolyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12h)

Yield: 0.71 g (64%); white needles; mp 306–307 °C (dec) (Me₂NCHO).

IR (KBr): 3297, 1892, 11744, 1634, 1589, 1558, 1488, 1443, 1391, 1327, 1299, 1284, 1237, 1173, 1070, 1064, 1005, 954, 857, 823, 800, 732, 629 cm^–1.

¹H NMR (CDCl₃+TFA-d ₁, 400 MHz): δ = 2.52 (s, 3 H), 5.12 (s, 2 H), 7.52 (d, J = 4 Hz, 1 H), 7.52 (m, 4 H), 7.71 (d, J = 8.2 Hz, 2 H), 7.84 (d, J = 8.2 Hz, 2 H).

¹³C NMR (CDCl₃+TFA-d ₁, 100.8 MHz): δ = 22.57 (CH₃), 49.88 (CH₂), 103.38 (C), 124.71 (C), 125.12 (CH), 129.71 (CH), 133.26 (CH), 135.64 (CH), 136.29 (C), 147.37 (C), 148.88 (C), 149.67 (C), 160.41 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₅BrN₃O: 368.0393; found: 368.0404.

5-p-Tolyl-2-phenyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12i)

Yield: 0.44 g (51%); white powder; mp 130–133 °C (dec) (Me₂CHOH/H₂O).

IR (KBr): 3467, 1735, 1589, 1495, 1440, 1389, 1328, 1199, 083, 955, 776, 733, 697 cm^–1.

¹H NMR (CDCl₃+TFA-d ₁, 400 MHz): δ = 2.38 (s, 3 H), 4.97 (s, 2 H), 6.72 (s, 1 H), 7.27 (s, 2 H), 7.55 (m, 4 H), 7.76 (m, 2 H).

¹³C NMR (CDCl₃+TFA-d ₁, 100.8 MHz): δ = 21.73 (CH₃), 46.94 (CH₂), 100.67 (CH), 121.61 (CH), 127.64 (CH), 130.05 (CH), 131.11 (CH), 134.88 (C), 137.77 (C), 142.65 (C), 148.77 (C), 160.75 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₆N₃O: 290.1288; found: 290.1294.

2-(Naphthalen-3-yl)-5-phenyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12j)

Yield: 0.53 g (54%); white powder; mp 170–172 °C (dec) (CHCl₃/pet ether).

IR (ATR): 2961, 1740, 1583, 1501, 1436, 1385, 1366, 1293, 1171, 970, 862, 794, 681 cm^–1.

¹H NMR (DMF-d ₇, 400 MHz): δ = 5.23 (s, 2 H), 7.11 (s, 1 H), 7.27 (t, J = 7.1 Hz, 2 H), 7.51 (t, J = 7.7 Hz, 2 H), 7.57 (m, 2 H), 7.86 (d, J = 8.3 Hz, 2 H), 7.98 (d, J = 7.0 Hz, 1 H), 8.00 (s, 2 H), 8.17 (d, J = 8.6 Hz, 1 H), 8.54 (s, 1 H).

¹³C NMR (DMF-d ₇, 100.8 MHz): δ = 45.95 (CH₂), 99.48 (CH), 120.40 (CH), 124.94 (CH), 125.60 (CH), 126.31 (CH), 127.43 (CH), 128.65 (CH), 129.25 (CH), 129.36 (CH), 130.05 (CH), 131.32 (C), 134.59 (C), 134.65 (C), 139.97 (C), 143.74 (C), 148.62 (C), 159.58 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₁₆N₃O: 326.1288; found: 326.1278.

2-(3-Bromophenyl)-5-phenyl-4,5-dihydroimidazo[1,5-b]pyrazol-6-one (12k)

Yield: 0.53 g (50%); white needles; mp 132–133 °C (dec) (EtOH).

IR (ATR): 3064, 1714, 1598, 1502, 1391, 1311, 1203, 1065, 785, 751, 679 cm^–1.

¹H NMR (DMSO-d ₆, 400 MHz): δ = 5.13 (s, 2 H), 7.08 (s, 1 H), 7.22 (t, J = 6.4 Hz, 1 H), 7.45 (q, J = 8.5 Hz, 3 H), 7.61 (d, J = 7.9 Hz, 1 H), 7.76 (d, J = 7.8 Hz, 2 H), 7.97 (d, J = 7.3 Hz, 1 H), 8.13 (s, 1 H).

¹³C NMR (DMSO-d ₆, 100.8 MHz): δ = 46.21 (CH₂), 100.06 (CH), 119.40 (C), 120.49 (CH), 123.64 (C), 126.00 (CH), 126.29 (CH), 129.73 (CH), 129.96 (C), 130.49 (CH), 132.46 (CH), 132.99 (CH), 139.67 (C), 144.02 (C), 148.50 (C), 157.68 (C).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₃BrN₃O: 354.0237; found: 354.0244.

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