3-(Trifluoromethyl)benzoyl chloride → 5-({[(3-Morpholin-4-ylpropyl)amino]carbonyl}amino)-3-(4-{[3-(trifluoromethyl)benzoyl]amino}phenyl)isothiazole-4-carboxamide

HRID 870999노트

반응식

HRID 870999 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]([NH2:15])=[O:14])=[C:11]([NH:16][C:17]([NH:19][CH2:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[O:18])[S:10][N:9]=2)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[F:38][C:39]([F:50])([F:49])[C:40]1[CH:41]=[C:42]([CH:46]=[CH:47][CH:48]=1)[C:43](Cl)=[O:44]>C1COCC1>[N:23]1([CH2:22][CH2:21][CH2:20][NH:19][C:17]([NH:16][C:11]2[S:10][N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:43](=[O:44])[C:42]4[CH:46]=[CH:47][CH:48]=[C:40]([C:39]([F:38])([F:49])[F:50])[CH:41]=4)=[CH:7][CH:6]=3)[C:12]=2[C:13]([NH2:15])=[O:14])=[O:18])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1

참가 물질

5

반응물 3

HCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 716213173-(4-Aminophenyl)-5-(3-(3-morpholinopropyl)ureido)isothiazole-4-carboxamide

생성물 1

HCID 716214735-({[(3-Morpholin-4-ylpropyl)amino]carbonyl}amino)-3-(4-{[3-(trifluoromethyl)benzoyl]amino}phenyl)isothiazole-4-carboxamide수율 80.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a mixture of 3-(4-aminophenyl)-5-(3-(3-morpholinopropyl)ureido)isothiazole-4-carboxamide (6 mg, 0.015 mmol) and N,N-diisopropylethylamine (0.0078 mL, 0.045 mmol) in 0.8 mL THF at rt was added 3-(trifluoromethyl)benzoyl chloride (0.0024 mL, 0.017 mmol). The reaction was stirred at rt for 2 hours, then quenched with aqueous Na2CO3 solution, stirred 5 min at rt, and then partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The solid was chromatographed eluting with CHCl3, then gradient 2.5% to 10% MeOH in CHCl3. The resulting solid was subjected to an EtOAc/NaHCO3 work-up to remove the presence of any silica gel impurity. Upon evaporation of the EtOAc layer the title compound was obtained as a white solid (7 mg, 76%).

후처리

  1. customquenched with aqueous Na2CO3 solution
  2. stirringstirred 5 min at rt
  3. custompartitioned between EtOAc and aqueous Na2CO3 solution
  4. washthe EtOAc layer washed with H2O, brine
  5. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  6. customThe solid was chromatographed
  7. washeluting with CHCl3
  8. customto remove the presence of any silica gel impurity
  9. customUpon evaporation of the EtOAc layer the title compound

출처 및 근거

ORD 기록
ord-45c6d15b1f8c45efa5cc7e8bd635c529
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969583B2

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