Ethylenediamine → 2-(6-chloro-1-methylindol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 245840노트

반응식

HRID 245840 반응식
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:41])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[CH:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:41])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[CH:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

참가 물질

5

반응물 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861872-(6-chloro-1-methyl-1H-indol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

생성물 1

HCID 712886932-(6-chloro-1-methylindol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide수율 66.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (54 mg, 0.091 mmol) was dissolved in dichloromethane (0.5 ml) and trifluoroacetic acid (0.28 ml, 3.63 mmol) was added. The dark red solution was stirred at room temperature for 2 h then concentrated. The residue was redissolved in dichloromethane (0.5 ml) and ethylenediamine (0.37 ml, 5.48 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 28 mg (63%) of 2-(6-chloro-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a yellow powder.

후처리

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in dichloromethane (0.5 ml)
  3. stirringThe reaction mixture was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resulting suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

출처 및 근거

ORD 기록
ord-a871f75a1d5542a4aca404567010a087
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

반응 노트

불러오는 중…