Sodium Hydroxide → 4-((5-Chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)(4-chloro-2-fluorophenyl)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylic acid

HRID 869077Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 869077
[Cl:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([NH:10][CH:11]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=2[F:42])[C:12]2[C:13]([C:30]([O:32]CC)=[O:31])=[N:14][N:15]([C:20]3[C:21]([O:28][CH3:29])=[N:22][C:23]([O:26][CH3:27])=[N:24][CH:25]=3)[C:16]=2[CH:17]([CH3:19])[CH3:18])[CH:3]=1.[OH-].[Na+]>C1COCC1.CO>[Cl:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([NH:10][CH:11]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=2[F:42])[C:12]2[C:13]([C:30]([OH:32])=[O:31])=[N:14][N:15]([C:20]3[C:21]([O:28][CH3:29])=[N:22][C:23]([O:26][CH3:27])=[N:24][CH:25]=3)[C:16]=2[CH:17]([CH3:18])[CH3:19])[CH:3]=1

Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 89602440ethyl 4-((5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)(4-chloro-2-fluorophenyl)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate

Produkt 1

HCID 896112354-((5-Chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)(4-chloro-2-fluorophenyl)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylic acidAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21899815MeOH tetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 465 mg (0.743 mmol) ethyl 4-((5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)(4-chloro-2-fluorophenyl)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate (product from step 184.2) in 7.42 ml THF/MeOH (1:1) under N2 atmosphere was cooled down to 0° C. After that 2.60 ml (5.20 mmol) of a 2M NaOH solution was added drop wise and the solution was stirred at 0° C. for 10 min and at RT for 1.5 hour. The solvent was evaporated, diluted in 50 ml CH2Cl2 and washed with 1M citric acid aqueous solution (30 ml). The water phase was extracted twice with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered and evaporated to give 461 mg (0.741 mmol, 100% yield) of the title compound as a foam, which was used in the next step without purification. LCMS: (M+H)=591/593; tR=0.97 min (LC-MS 4). HPLC: tR=4.69 min (HPLC 7). TLC: R=0.14 (CH2Cl2/MeOH 20:1).

Aufarbeitung

  1. customThe solvent was evaporated
  2. additiondiluted in 50 ml CH2Cl2
  3. washwashed with 1M citric acid aqueous solution (30 ml)
  4. extractionThe water phase was extracted twice with CH2Cl2
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-0a4cd230cb044168b111087bbf20efd2
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969341B2

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