Hydrochloric Acid → 4-[3-(7-tert-butylcarbamoyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-5-difluoromethoxy-indazol-1-yl]-butyric acid

HRID 246302

反応式

HRID 246302 の反応式
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[N:19]([CH2:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N)CN.Cl>ClCCl.O>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:28])[F:29])[CH:24]=4)[N:19]([CH2:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 4

HCID 313Hydrochloric Acid2 回HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712794494-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid

生成物 1

HCID 712803514-[3-(7-tert-butylcarbamoyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-5-difluoromethoxy-indazol-1-yl]-butyric acid収率 42.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

In a round-bottomed flask, 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-butyric acid (80 mg, 0.13 mmol) was dissolved in dichloromethane (0.7 ml) and trifluoroacetic acid (0.40 ml, 5.2 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.7 ml) and ethylenediamine (0.53 ml, 7.85 mmol) was added. The reaction was stirred at room temperature for 1 h then diluted with water and acidified with 1 M HCl then conc. HCl to pH=˜4. The resulting suspension was filtered and washed with hot water and ethyl acetate and the product was dried under high vacuum to provide 27 mg (41%) of 4-[3-(7-tert-butylcarbamoyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-5-difluoromethoxy-indazol-1-yl]-butyric acid as a brown powder. MS: (M+Na)+=509; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 9.09 (s, 1H), 8.39 (s, 1H), 8.22 (d, J=2.0 Hz, 1H), 7.86-7.92 (m, 2H), 7.42 (dd, J=9.1, 2.3 Hz, 1H), 7.21 (t, J=74.3 Hz, 1H), 4.59 (t, J=6.8 Hz, 2H), 2.26-2.33 (m, 2H), 2.08-2.19 (m, 2H), 1.51 (s, 9H).

後処理

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.7 ml)
  3. stirringThe reaction was stirred at room temperature for 1 h
  4. filtrationThe resulting suspension was filtered
  5. washwashed with hot water and ethyl acetate
  6. customthe product was dried under high vacuum

出典と根拠

ORDレコード
ord-deaf2f73e1c64ade8647b2806744c96f
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

関連ノート

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