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 2075314노트

반응식

HRID 2075314 반응식
[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]

참가 물질

4

반응물 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

생성물 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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
70 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b5f3c8769f954d8e960e46d43aefef0f
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919504B2

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