Phenyl isocyanate → 3-{4-[(Anilinocarbonyl)amino]phenyl}-5-({[(3-morpholin-4-ylpropyl)amino]carbonyl}amino)isothiazole-4-carboxamide

HRID 870994노트

반응식

HRID 870994 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.[C:38]1([N:44]=[C:45]=[O:46])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1COCC1>[NH:44]([C:45]([NH:1][C:2]1[CH:3]=[CH:4][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[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)=[O:18])[S:10][N:9]=2)=[CH:6][CH:7]=1)=[O:46])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

참가 물질

5

반응물 3

HCID 7672Phenyl isocyanateHCID 81531DiisopropylethylamineHCID 716213173-(4-Aminophenyl)-5-(3-(3-morpholinopropyl)ureido)isothiazole-4-carboxamide

생성물 1

HCID 866892193-{4-[(Anilinocarbonyl)amino]phenyl}-5-({[(3-morpholin-4-ylpropyl)amino]carbonyl}amino)isothiazole-4-carboxamide수율 77%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of 3-(4-aminophenyl)-5-(3-(3-morpholinopropyl)ureido)isothiazole-4-carboxamide (12 mg, 0.030 mmol), N,N-diisopropylethylamine (0.021 mL, 0.120 mmol), and phenyl isocyanate (0.0056 mL, 0.051 mmol) in 1.0 mL THF was stirred at rt for 19 hours. The reaction was quenched with 0.2 mL 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 to a white solid. 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 (12 mg, 77%).

후처리

  1. customThe reaction was quenched with 0.2 mL 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
  6. customrotary evaporated to a white solid
  7. customThe solid was chromatographed
  8. washeluting with CHCl3
  9. customto remove the presence of any silica gel impurity
  10. customUpon evaporation of the EtOAc layer the title compound

출처 및 근거

ORD 기록
ord-23812f0e26f3406e983fe598e3916a67
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969583B2

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