Water → 2-(5-difluoromethoxy-1-pyrrolidin-3-ylmethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246309ノート

反応式

HRID 246309 の反応式
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([CH2:13][N:14]2[C:22]3[C:17](=[CH:18][C:19]([O:23][CH:24]([F:26])[F:25])=[CH:20][CH:21]=3)[C:16]([C:27]3[N:28]=[C:29]4[C:35]([C:36](=[O:42])[NH:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][N:33](COCC[Si](C)(C)C)[C:30]4=[N:31][CH:32]=3)=[N:15]2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[C:38]([NH:37][C:36]([C:35]1[C:29]2[C:30](=[N:31][CH:32]=[C:27]([C:16]3[C:17]4[C:22](=[CH:21][CH:20]=[C:19]([O:23][CH:24]([F:25])[F:26])[CH:18]=4)[N:14]([CH2:13][CH:10]4[CH2:11][CH2:12][NH:8][CH2:9]4)[N:15]=3)[N:28]=2)[NH:33][CH:34]=1)=[O:42])([CH3:41])([CH3:39])[CH3:40]

参加物

7

反応物 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712801373-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-ylmethyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 712799282-(5-difluoromethoxy-1-pyrrolidin-3-ylmethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide収率 36.3%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

In a round-bottomed flask, 3-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-ylmethyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (134 mg, 0.188 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (0.58 ml, 7.53 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1 ml) and ethylenediamine (0.76 ml, 11.3 mmol) was added. The light yellow solution was stirred at room temperature for 45 min then water and ethyl acetate were added. The resulting suspension was filtered and washed with hot water and ethyl acetate then dried under high vacuum to provide 33 mg (35%) of 2-(5-difluoromethoxy-1-pyrrolidin-3-ylmethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow powder. MS: (M+H)+=484; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.06 (s, 1H), 8.38 (s, 1H), 8.21 (s, 1H), 7.94 (d, J=9.1 Hz, 1H), 7.88 (s, 1H), 7.40 (d, J=9.1 Hz, 1H), 7.20 (t, J=74.8 Hz, 1H), 4.50 (d, J=6.8 Hz, 2H), 2.58-2.97 (m, 6H), 1.69-1.84 (m, 1H), 1.51 (s, 9H).

後処理

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1 ml)
  3. stirringThe light yellow solution was stirred at room temperature for 45 min
  4. filtrationThe resulting suspension was filtered
  5. washwashed with hot water and ethyl acetate
  6. customthen dried under high vacuum

出典と根拠

ORDレコード
ord-9665667d24d5426a93bae24270eaf6db
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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