References
<A NAME="RM01206SS-1">1</A>
Present Address: Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg
30, 2340 Beerse, Belgium.
<A NAME="RM01206SS-2">2</A>
Present Address: Battelle, 505 King Avenue, Columbus, Ohio 43201, USA.
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<A NAME="RM01206SS-5">5</A> For an alternative approach to 3 via a carbonylative Sonogashira coupling-cyclization see:
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<A NAME="RM01206SS-11">11</A> For recent mechanistic studies and industrial application of the Sugasawa reaction,
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<A NAME="RM01206SS-14">14</A>
The yield was determined by a quantitative HPLC assay.
<A NAME="RM01206SS-15">15</A>
2-Isopropylamino-7-methoxy-4-methylene-4,9-dihydro-3-thia-1,9-diazabenz[f]azulen-10-one (11): 1H NMR (400 MHz, DMSO-d
6): δ = 1.14 (d, J = 6.4 H, 6 H), 3.72 (s, 3 H), 3.70-3.85 (m, 1 H), 5.30 (s, 1 H), 5.34 (s, 1 H), 6.70-6.75
(m, 2 H), 6.75 (d, J = 2.4 Hz, 1 H), 7.28 (d, J = 8.5 Hz, 1 H), 7.74 (d, J = 7.5 Hz, 1 H), 10.0 (s, 1 H). 13C NMR (100 MHz, DMSO-d
6): δ = 22.7, 46.3, 55.7, 106.4, 110.6, 116.8, 123.1, 130.1, 131.5, 137.0, 139.6, 160.2,
161.4, 163.9.
<A NAME="RM01206SS-16">16</A> Up to 50% of 11 was formed when the reaction was carried out at 50 °C. Electrophilic reaction of
2-aminothiazoles at C-5 is well precedented. In this case, it may be promoted by ionization
of the C-2 isopropylamino group, although usually strong bases like sodium amide have
been employed to obtain deprotonation at such amino groups. See:
Heterocyclic Compounds
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<A NAME="RM01206SS-17">17</A>
A manuscript describing the complete assembly of BILN 2061 using 3 is in preparation and will be published in due course.
