Ethylenediamine → 2-[6-fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 246254노트

반응식

HRID 246254 반응식
[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=4)[N:20]([CH2:28][C:29]4[CH:30]=[N:31][C:32]([N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)=[CH:33][CH:34]=4)[N:19]=3)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])[CH3:5].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=4)[N:20]([CH2:28][C:29]4[CH:30]=[N:31][C:32]([N:35]5[CH2:36][CH2:37][O:38][CH2:39][CH2:40]5)=[CH:33][CH:34]=4)[N:19]=3)[N:16]=2)[NH:11][CH:10]=1)=[O:8])[CH3:5]

참가 물질

5

반응물 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712883572-[6-fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

생성물 1

HCID 712884022-[6-fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide수율 81.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

2-[6-Fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide (50 mg, 0.074 mmol) was combined with dichloromethane (1 mL) and trifluoroacetic acid (0.17 ml, 2.22 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 (0.15 ml, 2.22 mmol) was added. After 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 33 mg (77%) of 2-[6-fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a light yellow solid. MS: (M+H)+=545; 1H NMR (DMSO-d6) δ: 9.14 (s, 1H), 8.52-8.60 (m, 1H), 8.45 (s, 1H), 8.31 (br. s., 1H), 8.19 (d, J=8.3 Hz, 1H), 7.89 (d, J=9.5 Hz, 1H), 7.63 (d, J=8.3 Hz, 1H), 7.16 (t, J=9.0 Hz, 1H), 6.79 (d, J=8.3 Hz, 1H), 5.63 (br. s., 2H), 4.37 (br. s., 1H), 3.65 (br. s., 4H), 3.44-3.57 (m, 2H), 3.39 (br. s., 4H), 3.27 (s, 3H), 1.30 (d, J=6.3 Hz, 3H).

후처리

  1. additionwas added
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  4. concentrationAfter 20 min the 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-230a71ac9ada4125968b988537ea4a8e
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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