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

HRID 1842904Notes

Reaction equation

HRID 1842904 reaction equation
[Si:1]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:22])[C:19]([OH:21])=O)=[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.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[Cl:55][C:56]1[CH:57]=[C:58]([N:62]2[C:66]([CH2:67][NH2:68])=[CH:65][C:64]([C:69]([F:72])([F:71])[F:70])=[N:63]2)[CH:59]=[CH:60][CH:61]=1>C(Cl)Cl>[Si:1]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:22])[C:19]([NH:68][CH2:67][C:66]3[N:62]([C:58]4[CH:59]=[CH:60][CH:61]=[C:56]([Cl:55])[CH:57]=4)[N:63]=[C:64]([C:69]([F:72])([F:71])[F:70])[CH:65]=3)=[O:21])=[CH:14][C:13]=2[F:23])[CH2:10][CH2:11]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66644230(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamineHCID 708164012-(4-(1-(Tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanoic acid

Product 1

HCID 708159202-(4-(1-(tert-butyldimethylsilyloxy)-cyclopropyl)-3-fluorophenyl)-N-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)propanamideYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)propanoic acid (190 mg, 0.56 mmol, 1 eq) in DCM (10 mL) was added DIPEA (0.29 mL, 1.68 mmol, 3 eq) followed by EDC.HCl (128 mg, 0.67 mmol, 1.2 eq) and HOBt (103 mg, 0.67 mmol, 1.2 eq) at RT and stirred for 10 min when (1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine (175 mg, 0.56 mmol) was added and the mixture stirred for 3 h. After completion of the reaction the reaction mixture was washed with H2O (15 mL), brine (10 mL), dried (Na2SO4) and the solvents evaporated. The crude product was purified by CC using EtOAc/PE (3:7) to get 2-(4-(1-(tert-butyldimethylsilyloxy)-cyclopropyl)-3-fluorophenyl)-N-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)propanamide (103 mg; 31%) as off white solid (TLC system: EtOAc/PE (3:7) Rf: 0.5).

Workup

  1. additionwas added
  2. customAfter completion of the reaction the reaction mixture
  3. washwas washed with H2O (15 mL), brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. customthe solvents evaporated
  6. customThe crude product was purified by CC

Sources & evidence

ORD record
ord-f288688769704c53b9e94b62741cede3
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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