Citric Acid → {3-[5-(5-Chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-phenyl}-acetic acid

HRID 2204389Notes

Reaction equation

HRID 2204389 reaction equation
C([O:3][C:4](=[O:42])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([C:14]2[N:18]([CH:19]([CH3:21])[CH3:20])[C:17]3[CH:22]([C:35]4[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=4)[N:23]([C:26]4[CH:31]=[C:30]([Cl:32])[C:29](=[O:33])[N:28]([CH3:34])[CH:27]=4)[C:24](=[O:25])[C:16]=3[CH:15]=2)[CH:7]=1)C.[Li+].[OH-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO.O>[Cl:32][C:30]1[C:29](=[O:33])[N:28]([CH3:34])[CH:27]=[C:26]([N:23]2[C:24](=[O:25])[C:16]3[CH:15]=[C:14]([C:8]4[CH:7]=[C:6]([CH2:5][C:4]([OH:42])=[O:3])[CH:11]=[CH:10][C:9]=4[O:12][CH3:13])[N:18]([CH:19]([CH3:21])[CH3:20])[C:17]=3[CH:22]2[C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)[CH:31]=1

Participants

6

Reactant 3

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 86703197{3-[5-(5-Chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-phenyl}-acetic acid ethyl ester

Product 1

HCID 72205540{3-[5-(5-Chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-phenyl}-acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of {3-[5-(5-chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-phenyl}-acetic acid ethyl ester (Step 118.1) (0.338 mmol) and LiOH (0.675 mmol) in MeOH (1.6 mL) and H2O (0.4 mL) was stirred at rt. After 4 h, the reaction mixture was acidified to pH 4 with 10% aqueous citric acid and extracted with EtOAc (2×). The combined organic phases were dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a white solid. tR: 6.18 min (HPLC 2); ESI-MS: tR=0.98 min, [M]+ 580/582/584 (LC-MS 1); TLC: Rf=0.24 (9:1 CH2Cl2/MeOH).

Workup

  1. extractionextracted with EtOAc (2×)
  2. dry with materialThe combined organic phases were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified

Sources & evidence

ORD record
ord-380ed82d132e423489897a78686d6d26
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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