1,1'-Carbonyldiimidazole → tert-butyl (S)-1-(5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

HRID 2075314ノート

反応式

HRID 2075314 の反応式
[CH3:1][NH:2][C:3]1[CH:4]=[C:5]([C:10]2[S:14][C:13]([N:15]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:16][C@@H:17]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[N:12][N:11]=2)[CH:6]=[CH:7][C:8]=1[NH2:9].[C:44](N1C=CN=C1)(N1C=CN=C1)=[O:45]>C1COCC1>[CH3:1][N:2]1[C:3]2[CH:4]=[C:5]([C:10]3[S:14][C:13]([N:15]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:16][C@@H:17]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:18][C:19]4[CH:20]=[CH:21][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:23][CH:24]=4)=[N:12][N:11]=3)[CH:6]=[CH:7][C:8]=2[NH:9][C:44]1=[O:45]

参加物

4

反応物 2

HCID 682631,1'-CarbonyldiimidazoleHCID 57991892tert-Butyl (S)-1-(5-(3-(methylamino)-4-aminophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

生成物 1

HCID 57991869tert-butyl (S)-1-(5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
70 °C

実験手順

The above mentioned crude tert-butyl (S)-1-(5-(3-(methylamino)-4-aminophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate was dissolved in 150 mL THF in a round bottom flask. To this flask was added a 50 mL THF solution of 1,1′-carbonyldiimidazole (1.37 g, 8.45 mmol). The mixture was stirred at 70° C. for 10 hours. After removing the solvent under reduced pressure, the remaining residue was mixed with 200 mL EtOAc. The organic solution was washed with water, three times with saturated ammonium chloride, and dried over sodium sulfate. After removing the solvent, the remaining residue was subjected to silica gel column chromatograph separation using 40% EtOAc in hexane as the eluant. There were two very close major spots on TLC (Rf=0.16, 0.17). The pure fractions for the bottom spot were combined. After removing the solvent, tert-butyl (S)-1-(5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.36 g) was obtained as a tan solid. LCMS (API-ES) m/z (%): 649.3 (100%, M++H); 1H NMR (400 MHz, CDCl3) δ ppm 1.21 (s, 9H) 1.42 (s, 9H) 2.83 (m, 1H) 2.98 (m, 1H) 3.40 (s, 3H) 3.93-4.09 (m, 1H) 4.21-4.44 (m, 2H) 4.97-5.13 (m, 1H) 7.05 (d, J=8.02 Hz, 1H) 7.32 (d, J=7.82 Hz, 2H) 7.50 (m, 3H) 7.60 (s, 1H) 9.24 (s, 1H).

後処理

  1. customAfter removing the solvent under reduced pressure
  2. additionthe remaining residue was mixed with 200 mL EtOAc
  3. washThe organic solution was washed with water, three times with saturated ammonium chloride
  4. dry with materialdried over sodium sulfate
  5. customAfter removing the solvent
  6. customthe remaining residue was subjected to silica gel column chromatograph separation
  7. customAfter removing the solvent

出典と根拠

ORDレコード
ord-b5f3c8769f954d8e960e46d43aefef0f
出典データセット
uspto-grants-2011_04
特許番号
US07919504B2

反応ノート

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