Lithium hydroxide, monohydrate → HCID 90281476, compound

Participants

Reaction Steps

tert-Butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-5-methoxy-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (380 mg, 0.9 mmol) was dissolved in 12 mL of THF/MeOH/H2O (3/2/1) and to it was added LiOH.H2O (116 mg, 2.7 mmol). The reaction mixture was allowed to stir at ambient temperature for 3 hours and then purified by RP HPLC eluting with acetonitrile/water to afford 220 mg of 2-(2-bromo-5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetic acid. Dissolved 200 mg of the above acid (0.7 mmol) and (S)-methyl 3-(3-allylphenyl)-2-aminopropanoate hydrochloride (197 mg, 0.77 mmol) in 5 mL of DMF and to it was added N,N-diisopropylethylamine (366 μL, 2.1 mmol). The reaction mixture was cooled down to 0° C. and to it was added HATU (319 mg, 8.4 mmol), and then it was allowed to stir at ambient temperature for 20 minutes. The reaction mixture was purified by RP HPLC eluting with acetonitrile/water (with 0.1% TFA) to afford 210 mg (0.43 mmol) of (S)-methyl 3-(3-allylphenyl)-2-(2-(2-bromo-5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)acetamido)propanoate which was dissolved in 5 mL of CH2Cl2 and cooled down to 0° C. To it were added N,N-diisopropylethylamine (0.15 mL, 0.86 mmol), di-tert-butyl carbonate (113 mg, 0.86 mmol) and 4-dimethylaminopyridine (5.2 mg, 0.04 mmol). The resulting mixture was allowed to stir for 5 minutes and then partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, dried over MgSO4, filtered and the filtrate was concentrated to dryness. It was purified by silica gel chromatography eluting with EtOAc/hexanes) to afford 230 mg of (S)-tert-butyl 3-(2-(3-(3-allylphenyl)-1-methoxy-1-oxopropan-2-ylamino)-2-oxoethyl)-2-bromo-5-methoxy-1H-pyrrolo[3,2-b]pyridine-1-carboxylate MS (m/z): 586.0 [M+H]+; HPLC retention time 4.86 min (5-99% acetonitrile:water with 0.05% formic acid).

Provenance & Evidence