Sodium bis(trimethylsilyl)amide → 3-(6-Chloro-5-fluoro-pyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one

HRID 1749380노트

반응식

HRID 1749380 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C@H:19]([N:21]2[CH:29]([CH3:30])[C:28]3[C:23](=[CH:24][C:25]([C:31]4[CH:32]=[N:33][N:34]([CH:36]5[CH2:41][CH2:40][CH2:39][CH2:38][O:37]5)[CH:35]=4)=[CH:26][CH:27]=3)[C:22]2=[O:42])[CH3:20])=[CH:15][CH:14]=1.Cl[C:44]1[C:49]([F:50])=[C:48]([Cl:51])[N:47]=[CH:46][N:45]=1>O1CCCC1.C(OCC)(=O)C.O>[Cl:51][C:48]1[N:47]=[CH:46][N:45]=[C:44]([C:29]2([CH3:30])[C:28]3[C:23](=[CH:24][C:25]([C:31]4[CH:32]=[N:33][N:34]([CH:36]5[CH2:41][CH2:40][CH2:39][CH2:38][O:37]5)[CH:35]=4)=[CH:26][CH:27]=3)[C:22](=[O:42])[N:21]2[C@@H:19]([C:16]2[CH:15]=[CH:14][C:13]([O:12][CH3:11])=[CH:18][CH:17]=2)[CH3:20])[C:49]=1[F:50]

참가 물질

7

반응물 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 112866754,6-Dichloro-5-fluoropyrimidineHCID 904082912-[(1R)-1-(4-Methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one

생성물 1

HCID 904080383-(6-Chloro-5-fluoro-pyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one수율 103%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

Add sodium bis(trimethylsilyl)amide (210 mL, 210 mmol, 1 M THF) drop wise over 60 minutes to an ice cold suspension of 2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one (62 g, 144 mmol) and 4,6-dichloro-5-fluoropyrimidine (31 g, 186 mmol) in tetrahydrofuran (620 mL). Stir the solution 60 minutes at 0° C. and then dilute the mixture with ethyl acetate (1 L) and water (1 L). Wash the organic phase with saturated aqueous sodium chloride and evaporate under reduced pressure. Dissolve the residue in 1:1 petroleum ether/ethyl acetate, filter through a pad of silica gel, and evaporate to give the title compound as a yellow foam (83 g, 103%). ES/MS m/z: 562 (M+H).

후처리

  1. washWash the organic phase with saturated aqueous sodium chloride
  2. customevaporate under reduced pressure
  3. dissolutionDissolve the residue in 1:1 petroleum ether/ethyl acetate
  4. filtrationfilter through a pad of silica gel
  5. customevaporate

출처 및 근거

ORD 기록
ord-247e438b108e466dae7d5cb2d45e977b
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156824B2

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