1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxypropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Participants

Reaction Steps

A mixture of 2-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (200 mg, 0.638 mmol), (S)-2-aminopropan-1-ol (57 mg, 0.765 mmol), EDCI (366 mg, 1.914 mmol), HOBt (258 mg, 1.914 mmol) and DIPEA (247 mg, 1.914 mmol) in dry DMF (10 mL) was stirred for 16 hours at room temperature. Water (10 mL) was added, the formed precipitate was separated by filtration, washed with methanol (1 mL) then was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 30% acetonitrile/70% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 60% acetonitrile/40% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min.) to afford (S)-2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxypropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (46 mg, 26% for two steps) as a yellow solid. LCMS: (M+H)+=371; 1H NMR (300 MHz, DMSO+D2O): δ 9.14 (s, 1H), 8.59 (d, 1H, J=8.7 Hz), 8.36 (s, 1H), 7.72 (s, 1H), 7.27 (dd, 1H, J1=8.4 Hz, J2=1.8 Hz), 4.23-4.18 (m, 1H), 3.55 (d, 1H, J=4.2 Hz), 1.25 (d, 1H, J=6.6 Hz).

Provenance & Evidence