Ethylenediamine → 2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide

HRID 246266노트

반응식

HRID 246266 반응식
[CH3:1][CH:2]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH2:32][CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[N:23]=3)[N:20]=2)[N:15](COCC[Si](C)(C)C)[CH:14]=1)=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][CH:2]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH2:32][CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[N:23]=3)[N:20]=2)[NH:15][CH:14]=1)=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1

참가 물질

5

반응물 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712883782-[6-Fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)amide

생성물 1

HCID 712883822-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide수율 43.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

2-[6-Fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)amide (75 mg, 0.117 mmol) was combined with dichloromethane (1 mL) then trifluoroacetic acid (0.26 ml, 3.50 mmol) was added. After stirring for 2 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (1 mL) and ethylenediamine (0.23 ml, 3.50 mmol) was added and the reaction was stirred at room temperature for 20 min. The reaction mixture was concentrated in vacuo and the residue was triturated with water (2 mL). The precipitate was filtered, washed with water and dried to afford 26 mg (41%) of 2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide (26 mg, 41%) as a yellow solid. MS: (M+H)+=513; 1H NMR (DMSO-d6) δ: 9.07 (s, 1H), 8.32-8.44 (m, 2H), 8.22 (d, J=8.3 Hz, 1H), 7.73 (d, J=9.8 Hz, 1H), 7.50-7.66 (m, 2H), 7.27 (d, J=7.8 Hz, 1H), 7.03-7.16 (m, 2H), 4.53-4.67 (m, 4H), 4.46 (s, 1H), 3.02-3.25 (m, 2H), 2.98 (t, J=6.5 Hz, 3H), 1.64 (br. s., 5H), 1.29 (d, J=6.5 Hz, 3H).

후처리

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  3. stirringthe reaction was stirred at room temperature for 20 min
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue was triturated with water (2 mL)
  6. filtrationThe precipitate was filtered
  7. washwashed with water
  8. customdried

출처 및 근거

ORD 기록
ord-7594e4ca97c74bc09894f3a4ecb8b896
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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