Ethylenediamine → 2-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246344

反応式

HRID 246344 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][C:31]4[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=4)[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>C(Cl)Cl>[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][C:31]4[CH:32]=[N:33][N:34]([CH3:36])[CH:35]=4)[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712795822-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

生成物 1

HCID 712798962-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide収率 65.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 2-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (56 mg, 0.09 mmol) in CH2Cl2 (2 mL) was added trifluoroacetic acid (0.5 mL, 6.5 mmol). The reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was dissolved in CH2Cl2 (2 mL) and ethylenediamine (0.2 mL, 2.96 mmol) was added. The reaction mixture was stirred at room temperature for 30 min then quenched with water and extracted with 5% MeOH/CH2Cl2. The organics were dried over MgSO4 and concentrated. The residue was triturated with EtOAc/Et2O and the product was collected via filtration to afford 29 mg (65%) of 2-[5-difluoromethoxy-1-(1-methyl-1H-pyrazol-4-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow solid. MS: (M+Na)+=517; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.62 (br. s., 1H), 8.97 (s, 1H), 8.26 (s, 1H), 8.06 (d, J=1.9 Hz, 1H), 7.85 (d, J=9.1 Hz, 1H), 7.74 (s, 1H), 7.65 (s, 1H), 7.38 (s, 1H), 7.27 (dd, J=9.1, 1.9 Hz, 1H), 7.06 (7, J=75 Hz, 1H), 5.51 (s, 2H), 3.19 (s, 6H), 1.36 (s, 9H).

後処理

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in CH2Cl2 (2 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 30 min
  4. customthen quenched with water
  5. extractionextracted with 5% MeOH/CH2Cl2
  6. dry with materialThe organics were dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was triturated with EtOAc/Et2O
  9. filtrationthe product was collected via filtration

出典と根拠

ORDレコード
ord-1a6fcc3aa03c4830b51b3831db26e9a6
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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