Acetic Acid → 1-(4'-{5-[3-(4-Chloro-phenyl)-1-methyl-propylamino]-1-methyl-1H-pyrazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid ethyl ester

HRID 919089Notes

Reaction equation

HRID 919089 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[N:23][N:24]([CH3:27])[C:25]=4[NH2:26])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C:37](=O)[CH3:38])=[CH:31][CH:30]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[N:23][N:24]([CH3:27])[C:25]=4[NH:26][CH:37]([CH3:38])[CH2:36][CH2:35][C:32]4[CH:31]=[CH:30][C:29]([Cl:28])=[CH:34][CH:33]=4)=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2192774-(4-chlorophenyl)butan-2-oneHCID 5003444Sodium cyanoborohydride2×HCID 679595561-[4'-(5-Amino-1-methyl-1H-pyrazol-4-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 679595641-(4'-{5-[3-(4-Chloro-phenyl)-1-methyl-propylamino]-1-methyl-1H-pyrazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

1-[4′-(5-Amino-1-methyl-1H-pyrazol-4-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester (0.125 g, 0.346 mmol) and 4-(4-chloro-phenyl)-butan-2-one (0.095 g, 0.52 mmol) were dissolved in MeOH (5 mL). Acetic acid (0.030 mL, 0.52 mmol) was added along with a few molecular sieves and the reaction stirred at 30° C. overnight. Sodium cyanoborohydride (0.033 g, 0.52 mmol) was then added and the reaction was heated to 60° C. for 4 hours. An additional 0.5 equivalents of sodium cyanoborohydride was added and the reaction continued heating for 1 hour. All solvent was removed and the residue was submitted to EtOAc/H2O workup. The residue was purified twice on silica gel (0-100% EtOAc in hexanes followed by 0-10% MeOH in CH2Cl2) to afford the title compound.

Workup

  1. temperaturethe reaction was heated to 60° C. for 4 hours
  2. temperaturethe reaction continued heating for 1 hour
  3. customAll solvent was removed
  4. customThe residue was purified twice on silica gel (0-100% EtOAc in hexanes followed by 0-10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-9c1cae1d25234f67ba326d71a49ad2ed
Source dataset
uspto-grants-2016_03
Patent number
US09272990B2

Reaction notes

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