(R)-methyl 2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanoate → (R)-2-(4-Chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanoic acid

HRID 711567Notes

Reaction equation

[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@H:25]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:26]([O:28]C)=[O:27])[N:3]=1>CO.[OH-].[Na+]>[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@H:25]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:26]([OH:28])=[O:27])[N:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of (R)-methyl 2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanoate (2.9 g, 6.04 mmol) in MeOH (10 mL) and 1N NaOH (40.0 mL) was stirred at 50° C. for 2 h. UPLC showed 30% starting material remained. Additional saturated NaOH solution (5 mL) was added and the reaction mixture was stirred for 3 h at 50° C. The solvent was removed and the resulting residue was dispersed in H2O (100 mL) and acidified to pH 3 using HCl. After stirring at RT for 2 h, the solid was filtered to give the title compound. [M+H] calc'd for C22H25ClFN3O5, 466. found, 466.

Workup

stirringthe reaction mixture was stirred for 3 h at 50° C
customThe solvent was removed
additionthe resulting residue was dispersed in H2O (100 mL)
stirringAfter stirring at RT for 2 h
filtrationthe solid was filtered

Sources & evidence

ORD record: ord-cc9a6cf4a59b40248ee97f99056827f1
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181255B2

Reaction notes

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