Tert-Butylamine → N-tert-Butyl-2-(6-fluoro-1-(2-morpholino-2-oxoethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246269ノート

反応式

HRID 246269 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[N:21]=[C:22]4[C:28]([C:29]([OH:31])=O)=[CH:27][N:26]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:23]4=[N:24][CH:25]=3)=[N:7][N:8]2[CH2:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:52]([NH2:56])([CH3:55])([CH3:54])[CH3:53]>C1COCC1>[C:52]([NH:56][C:29]([C:28]1[C:22]2[C:23](=[N:24][CH:25]=[C:20]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]([CH2:11][C:12]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)=[O:13])[N:7]=3)[N:21]=2)[N:26]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:37])([CH3:38])[CH3:39])[CH:27]=1)=[O:31])([CH3:55])([CH3:54])[CH3:53]

参加物

5

反応物 3

HCID 6385Tert-ButylamineHCID 682631,1'-CarbonyldiimidazoleHCID 712800952-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 1

HCID 71280344N-tert-Butyl-2-(6-fluoro-1-(2-morpholino-2-oxoethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide収率 70%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

In a 15 ml round-bottomed flask, 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (110 mg, 0.20 mmol) was suspended in THF (3 ml) and 1,1′-carbonyldiimidazole (39 mg, 0.24 mmol) was added. The light yellow suspension was stirred at 60° C. for 45 min during which time all solids dissolved. The reaction mixture was cooled to room temperature, tert-butylamine (0.20 ml, 1.9 mmol) was added, and the reaction was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-80% EtOAc) to afford 84 mg (70%) of 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white solid.

後処理

  1. dissolutiondissolved
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringthe reaction was stirred at room temperature overnight
  4. customThe reaction mixture was quenched with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-80% EtOAc)

出典と根拠

ORDレコード
ord-14ec1fb4e65f476489de835396448f41
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…