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 1749380ノート

反応式

HRID 1749380 の反応式
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]

参加物

7

反応物 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

生成物 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-one収率 103%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-247e438b108e466dae7d5cb2d45e977b
出典データセット
uspto-grants-2015_10
特許番号
US09156824B2

反応ノート

読み込み中…