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 869077노트

반응식

HRID 869077 반응식
[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

참가 물질

4

반응물 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

생성물 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 acid수율 100%

시약·촉매·용매 1

HCID 21899815MeOH tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-0a4cd230cb044168b111087bbf20efd2
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969341B2

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