A Facile Approach to the Synthesis of 3-(6-Chloro-thiazolo[5,4-b]pyridin-2-ylmethoxy)-2,6-difluoro-benzamide (PC190723)

Abstract

Practical synthesis of PC 190723, a bacterial cell division protein Ftsz inhibitor, has been achieved in a high overall yield of 45% in six steps from commercially available starting materials.

Key words

antibacterial agents - cell division inhibitors - thiazolo[5,4-b]pyridine - FtsZ

• References and Notes

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• 9 Analytical and spectral data: beige solid; mp 166–168 °C; ¹H NMR (400 MHz, CDCl₃): δ = 6.29 (d, J = 9.2 Hz, 1 H), 7.43 (d, J = 9.6 Hz, 1 H), 14.10 (s, 1 H), 15.00 (br s, 1 H); MS (ESI): m/z = 203.04 [M + Na]⁺; HRMS (ESI): m/z [M⁺ + Na]⁺ calcd for C₇H₄N₂O₄: 203.0069; found: 203.0070
• 10 Analytical and spectral data: yellow solid; mp 220–222 °C; ¹H NMR (400 MHz, DMSO-d ₆): δ = 5.72 (s, 2 H), 7.10 (td, J = 9.0, 2.0 Hz, 1 H), 7.41 (td, J = 9.2, 5.2 Hz, 1 H), 7.81 (br s, 1 H), 8.10 (br s, 1 H), 8.65 (d, J = 2.4 Hz, 1 H), 8.72 (d, J = 2.0 Hz, 1 H); MS (ESI): m/z = 378.04 [M + Na]⁺, 394.02 [M + K]⁺. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 170.85, 161.12, 155.67, 152.83 (dd, J = 240.35, 6.3 Hz), 148.33 (dd, J = 247.95, 9.6 Hz), 146.20, 145.95, 141.97 (dd, J = 11.2, 3.3 Hz), 129.92, 129.36, 117.16–116.71 (m), 111.32 (d, J = 4.2 Hz), 111.09 (d, J = 3.2 Hz), 69.29; ¹⁹F NMR (500 MHz, DMSO-d ₆): δ = –122.78 (dd, J = 10.0, 5.0 Hz, 6-F), –133.55 (d, J = 10.0 Hz, 2-F); MS (ESI): m/z = 378.04 [M + Na]⁺, 394.02 [M + K]⁺; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₈ClF₂N₃O₂S: 377.9892; found: 377.9895