Phosgene → Cyclobutyl-6-bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

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Reaction Steps

6-bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine (Preparation 122, 100 mg, 0.36 mmol) was dissolved in dry DMF (1 ml). The solution was degassed and a solution of sodium bis(trimethylsilyl)amide (0.54 ml of a 1M solution in THF, 0.54 mmol) was added. After 20 minutes reaction, a solution of cyclobutylchloroformate [freshly prepared by stirring 40 mg of cyclobutanol with one equivalent of a 20% phosgene solution in toluene (0.275 ml) for 3 h, 0.55 mmol] was added. The reaction was stirred for 2 hours at room temperature then was diluted with ethyl acetate and water. The organic solution was washed with brine, dried over sodium sulphate and concentrated in vacuum. The crude product was purified on silica gel column chromatography eluting with 20% hexane in ethyl acetate to afford the title compound as a white powder (95 mg, 70.2%). 1H-NMR (500 MHz, CDCl3): δ 1.69 (m, 1H), 2.12 (m, 1H), 2.15 (m, 2H), 2.4 (m, 2H), 3.94 (s, 3H), 5.17 (quin, J=7.2 Hz, 1H), 6.54 (s, 1H), 7.6 (s, 1H), 7.62 (s, 1H), 8.14 (s. 1H), 8.51 (s, 1H)

Provenance & Evidence