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

HRID 1842897Notes

Reaction equation

HRID 1842897 reaction equation
[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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-8e564ac2ba6049babb07e1aafd4051b1
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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