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 2204418Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2204418
[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

Komponenten

4

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21899815MeOH tetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-9513472df4484d37a4d4a2ed9f6ce0f2
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365576B2

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