Triethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-cyanomethyl-pyrrolidin-3-yl)-amide

HRID 246232노트

반응식

HRID 246232 반응식
[NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[C:26]5[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=5)[N:20]([CH3:28])[N:19]=4)[N:16]=3)[N:11]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:10]=2)=[O:8])[CH2:2]1.[CH2:37]([N:39](CC)CC)[CH3:38]>ClCCl.BrCC#N>[C:37]([CH2:38][N:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[C:26]5[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=5)[N:20]([CH3:28])[N:19]=4)[N:16]=3)[N:11]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:10]=2)=[O:8])[CH2:2]1)#[N:39]

참가 물질

5

반응물 2

HCID 8471TriethylamineHCID 712883352-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (R)-pyrrolidin-3-ylamide

생성물 1

HCID 866779632-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-cyanomethyl-pyrrolidin-3-yl)-amide수율 45%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 11534Bromoacetonitrile용매

실험 절차

2-(6-Fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (R)-pyrrolidin-3-ylamide from Step 1 was dissolved in dichloromethane with the addition of triethylamine and bromo-acetonitrile. The reaction was concentrated and dried from mixtures of dichloromethane and hexanes. The crude was dissolved in a mixture dichloromethane, tetrahydrofuran, and methanol, supported on silica gel and purified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane (0.5% Et3N). The appropriate fractions were combined and concentrated. The solid obtained was triturated with Et2O and hexanes. The solid was discarded and the mother liquor was concentrated to afford 220 mg (45%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-cyanomethyl-pyrrolidin-3-yl)-amide as a white solid, 220 mg (45% yield). LC-MS (M+H)+=549.

후처리

  1. concentrationThe reaction was concentrated
  2. dry with materialdried from mixtures of dichloromethane and hexanes
  3. dissolutionThe crude was dissolved in a mixture dichloromethane, tetrahydrofuran, and methanol
  4. custompurified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane (0.5% Et3N)
  5. concentrationconcentrated
  6. customThe solid obtained
  7. customwas triturated with Et2O and hexanes
  8. concentrationthe mother liquor was concentrated

출처 및 근거

ORD 기록
ord-63e0407c83e942298d0fa81b70ceefa0
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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