Diboron → HCID 53636997, compound

Participants

Reaction Steps

To a solution of 2-(S)-benzyloxycarbonylamino-4-(2-pyrrolo[3,2-c]pyridin-1-yl-acetylamino)-butyric acid methyl ester (0.51 g, 1.20 mmol) in THF (5 mL) is added diborane (5 mL, 0.500 mmol, 1 M solution in THF). The resulting mixture is stirred at room temperature for 4 hours and then concentrated in vacuo. The residue is suspended in EtOAc (10 mL), treated with 10 drops of H2O, 5 drops of 1 N NaOH and further quenched with saturated NH4Cl solution. The mixture is concentrated in vacuo to about ½ volume, partitioned between EtOAc and 10% Na2CO3 solution and the layers are separated. The aqueous layer is extracted with EtOAc. The combined organic phases are washed with saturated NaCl, dried over MgSO4, filtered and concentrated in vacuo. The crude product obtained is partially purified by column chromatography in a gradient of 2% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2 to afford [2-oxo-1-(2-pyrrolo[3,2-c]pyridin-1-yl-ethyl)-pyrrolidin-3-(S)-yl]-carbamic acid benzyl ester. FAB MS, [M+H]+=379. To a solution of this crude [2-oxo-1-(2-pyrrolo[3,2-c]pyridin-1-yl-ethyl)-pyrrolidin-3-(S)-yl]-carbamic acid benzyl ester in MeOH (10 mL) and AcOH (3 mL) is added a catalytic amount of 10% palladium on activated carbon. The heterogenous mixture is stirred at room temperature under a balloon of H2 for 18 hours. The reaction mixture is filtered through a pad of Celite and washed with MeOH (3×). The crude product is concentrated in vacuo and then azeotroped with toluene to give 3-(S)-amino-1-(2-pyrrolo[3,2-c]pyridin-1-yl-ethyl)-pyrrolidin-2-one acetate as a residue (wet with excess HOAc). FAB MS, [M+H]+=245. The title compound is prepared in CH2Cl2 instead of CH3CN as described in EXAMPLE 1, Part K using the above 3-(S)-amino-1-(2-pyrrolo[3,2-c]pyridin-1-yl-ethyl)-pyrrolidin-2-one acetate in place of 7-(3-(S)-amino-2-oxopyrrolidin-1-ylmethyl)-1-chloro-isoquinoline hydrochloride and 7-methoxynaphthalene-2-sulfonyl chloride as prepared in EXAMPLE 1, Part J. The crude product is partially purified by column chromatography eluting in a gradient of 3% MeOH/CH2Cl2 to 5% MeOH/CH2Cl2. The residue obtained is further purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 80% CH3CN/H2O (0.1% TFA) and the appropriate product fractions are lyophilized to provide the title compound as a white solid.

Provenance & Evidence