Sodium Hydroxide → 5-(5-Chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrole-3-carboxylic acid

HRID 2204418Notes

Reaction equation

HRID 2204418 reaction equation
[OH-].[Na+].C([O:5][C:6]([C:8]1[C:9]2[C:28](=[O:29])[N:27]([C:30]3[CH:35]=[C:34]([Cl:36])[C:33](=[O:37])[N:32]([CH3:38])[CH:31]=3)[CH:26]([C:39]3[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=3)[C:10]=2[N:11]([CH:23]([CH3:25])[CH3:24])[C:12]=1[C:13]1[C:14]([O:21][CH3:22])=[N:15][C:16]([O:19][CH3:20])=[N:17][CH:18]=1)=[O:7])C>C1COCC1.CO>[Cl:36][C:34]1[C:33](=[O:37])[N:32]([CH3:38])[CH:31]=[C:30]([N:27]2[C:28](=[O:29])[C:9]3[C:8]([C:6]([OH:7])=[O:5])=[C:12]([C:13]4[C:14]([O:21][CH3:22])=[N:15][C:16]([O:19][CH3:20])=[N:17][CH:18]=4)[N:11]([CH:23]([CH3:25])[CH3:24])[C:10]=3[CH:26]2[C:39]2[CH:40]=[CH:41][C:42]([Cl:45])=[CH:43][CH:44]=2)[CH:35]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 867032385-(5-Chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 867032395-(5-Chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

2N Aqueous NaOH (0.208 mmol) was added to a solution of 5-(5-chloro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-4-oxo-1,4,5,6-tetrahydro-pyrrolo[3,4-b]pyrrole-3-carboxylic acid ethyl ester (Example 220) (0.104 mmol) in 1:1 THF/MeOH (2 mL) and the mixture was stirred at 80° C. for 1 h. After evaporation of MeOH, the pH was adjusted to 5 with addition of 10% w/w aqueous citric acid and extracted with EtOAc (3×). The combined organic phases were successively washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The residue was purified by SFC to afford the title compound as a white solid. tR: 1.10 min (HPLC 3); ESI-MS: tR=0.97 min, [M+H]+ 598/600/602 (LC-MS 1); TLC: Rf=0.31 (9:1 CH2Cl2/MeOH).

Workup

  1. customAfter evaporation of MeOH
  2. additionthe pH was adjusted to 5 with addition of 10% w/w aqueous citric acid
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organic phases were successively washed with H2O and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by SFC

Sources & evidence

ORD record
ord-9513472df4484d37a4d4a2ed9f6ce0f2
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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