Benzoic Acid → (5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide benzoate

HRID 69552Notes

Reaction equation

HRID 69552 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:10][C:11]([F:53])([F:52])[C:12]1[CH:13]=[C:14]([C:22]([CH3:51])([CH3:50])[C:23]([N:25]([CH3:49])[C:26]2[C:27]([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=3[CH3:48])=[CH:28][C:29]([C@@H:32]3[NH:36][C@@:35]([CH3:40])([C:37]([NH2:39])=[O:38])[CH2:34][CH2:33]3)=[N:30][CH:31]=2)=[O:24])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1>C1(C)C=CC=CC=1>[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:53][C:11]([F:10])([F:52])[C:12]1[CH:13]=[C:14]([C:22]([CH3:50])([CH3:51])[C:23]([N:25]([CH3:49])[C:26]2[C:27]([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=3[CH3:48])=[CH:28][C:29]([C@@H:32]3[NH:36][C@@:35]([CH3:40])([C:37]([NH2:39])=[O:38])[CH2:34][CH2:33]3)=[N:30][CH:31]=2)=[O:24])[CH:15]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:17]=1

Participants

4

Reactant 2

HCID 243Benzoic AcidHCID 44472503(5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide2×

Product 1

HCID 86636101(5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide benzoateYield 62.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
40 °C

Procedure

Toluene (3.5 ml) was added to benzoic acid (102.65 mg, 1 eg) in order to dissolve the acid. The acid solution was then added to 500 mg of (5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide (Example 1). After heating to 40° C. and then cooling down to 20° C., the reaction was seeded with benzoate crystals of Example 1 which were obtained through a small scale evaporation experiment (50 mg) from toluene). The reaction was then temperature cycled for 3 days. The solid which formed was isolated and allowed to dry at 45° C. overnight to obtain the title compound (374 mg) as a crystalline form. Onset melt 131° C. by DSC.

Workup

  1. dissolutionto dissolve the acid
  2. temperaturecooling down to 20° C.
  3. customThe solid which formed
  4. customwas isolated
  5. customto dry at 45° C. overnight

Sources & evidence

ORD record
ord-a9bae647380a4b9e84ecc84cc7fb730d
Source dataset
uspto-grants-2014_09
Patent number
US08822504B2

Reaction notes

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