1-Hydroxybenzotriazole → N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanamide

HRID 1842897노트

반응식

HRID 1842897 반응식
[Si:1]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:22])[C:19](O)=[O:20])=[CH:14][C:13]=2[F:23])[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[C:65]([C:69]1[CH:73]=[C:72]([CH2:74][NH2:75])[N:71]([C:76]2[CH:81]=[CH:80][CH:79]=[C:78]([Cl:82])[CH:77]=2)[N:70]=1)([CH3:68])([CH3:67])[CH3:66]>C1COCC1.CN(C=O)C.CCOC(C)=O>[C:65]([C:69]1[CH:73]=[C:72]([CH2:74][NH:75][C:19](=[O:20])[CH:18]([C:15]2[CH:16]=[CH:17][C:12]([C:9]3([O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3])[CH2:10][CH2:11]3)=[C:13]([F:23])[CH:14]=2)[CH3:22])[N:71]([C:76]2[CH:81]=[CH:80][CH:79]=[C:78]([Cl:82])[CH:77]=2)[N:70]=1)([CH3:68])([CH3:66])[CH3:67]

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58093530(3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methanamineHCID 708164012-(4-(1-(Tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanoic acid

생성물 1

HCID 70816356N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanamide수율 61.2%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 21974620tetrahydrofuran N,N-dimethylformamide용매

실험 절차

To a stirred solution of 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanoic acid (135 mg, 0.400 mmol, 1 eq) in THF/DMF (3 mL/0.15 mL) was added DIPEA (0.271 mL, 1.6 mmol, 4 eq) followed by TBTU (131 mg, 0.400 mmol, leg) and HOBt (131 mg, 0.400 mmol, 1 eq) at RT and the mixture was stirred for 3 h, then (3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methanamine (175 mg, 0.56 mmol) was added and the mixture stirred for another 36 h. After completion of the reaction the reaction EtOAc was added and the mixture was washed with H2O (15 mL), dried (Na2SO4) and the solvent evaporated. The crude product was purified by CC using EtOAc/cyclohexane (1:4) to get N-((3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methyl)-2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanamide (143 mg; 61%).

후처리

  1. stirringthe mixture stirred for another 36 h
  2. customAfter completion of the reaction
  3. additionwas added
  4. washthe mixture was washed with H2O (15 mL)
  5. dry with materialdried (Na2SO4)
  6. customthe solvent evaporated
  7. customThe crude product was purified by CC

출처 및 근거

ORD 기록
ord-8e564ac2ba6049babb07e1aafd4051b1
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946204B2

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