4-Azido-1H-pyrrolo[2,3-b]pyridine synthesis

Yield:361370-27-6 66%

Reaction Conditions:

with sodium azide;ammonium chloride in N,N-dimethyl-formamide at 110;

Steps:

1H-4-azido-pyrrolo[2,3-b]pyridine] (FH6353)

1H-4-chloro-pyrrolo[2,3-b]pyridine (0.765 g, 5 mmol, 1 eq.) was dissolved in DMF (15 mL, 3 mL / mmol SM), and NH₄CI (1 .34 g, 25 mmol, 5 eq.) were added, followed by NaN₃ (1 .63 g, 25 mmol, 5 eq.). The mixture was heated to 1 10°C. After 7 H, the mixture was allowed to cool to ambient temperature, diluted with EA, and poured into half-sat. aq. NaHC0₃ solution. The layers were separated and the water layer washed twice with EA. The organic layers were combined, dried over Na₂S0₄, filtered and evaporated till dryness. The residue was purified by column chromatography (30 % EA/PET) to give FH6353 (0.53 g, 3.32 mmol) as a white solid in 66 % yield. ¹H NMR (300 MHz, DMSO-d₆) δ: 6.46 (dd, J = 3.3, 1 .8 Hz, 1 H , H-3), 6.88 (d, J = 5.4 Hz, 1 H, H-5), 7.46 (dd, J = 3.6, 2.4 Hz, 1 H, H-2), 8.18 (d, J = 5.1 Hz, 1 H, H-6), 1 1 .86 (br. s, 1 H, NH). ¹³C NMR (75 MHz, DMSO-d₆) δ: 96.94 (C-3), 105.03 (C-5), 1 1 1 .99 (C-3a), 125.89 (C-2), 139.45 (C-7a), 143.72 (C-6), 149.94 (C-4). HRMS (ESI): calculated for C₇H₆N₅ [M+H]⁺): 160.0618, found: 160.0585. Melting point: 180 °C (decomposed).

References:

WO2019/76633,2019,A1 Location in patent:Page/Page column 36; 67