Citric 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 citrate

HRID 69553Notes

Reaction equation

HRID 69553 reaction equation
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([C:13]([CH3:42])([CH3:41])[C:14]([N:16]([CH3:40])[C:17]2[C:18]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=3[CH3:39])=[CH:19][C:20]([C@@H:23]3[NH:27][C@@:26]([CH3:31])([C:28]([NH2:30])=[O:29])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:45]([OH:57])(=[O:56])[CH2:46][C:47]([CH2:52][C:53]([OH:55])=[O:54])([C:49]([OH:51])=[O:50])[OH:48]>C1(C)C=CC=CC=1>[C:45]([OH:57])(=[O:56])[CH2:46][C:47]([CH2:52][C:53]([OH:55])=[O:54])([C:49]([OH:51])=[O:50])[OH:48].[F:44][C:2]([F:1])([F:43])[C:3]1[CH:4]=[C:5]([C:13]([CH3:41])([CH3:42])[C:14]([N:16]([CH3:40])[C:17]2[C:18]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=3[CH3:39])=[CH:19][C:20]([C@@H:23]3[NH:27][C@@:26]([CH3:31])([C:28]([NH2:30])=[O:29])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

4

Reactant 2

HCID 311Citric 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-prolinamide

Product 1

HCID 86636102(5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide citrate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

25 mg of (5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methy)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide (Example 1) were dispensed into a HPLC vial followed by 7.6 mg (1 eq) citric acid. 250 μL of toluene were then dispensed on to the solid and the reaction was set to temperature cycle (0-40° C.) whilst stirring at 500 rpm. After 2.5 days, the solid was isolated by filtration at ambient. Onset melt ca.90° C. by DSC followed by decomposition.

Workup

  1. customwas set to temperature cycle (0-40° C.)
  2. customthe solid was isolated by filtration at ambient
  3. custom90° C.

Sources & evidence

ORD record
ord-4f9d87b1baf54162b16922ec3bb1320e
Source dataset
uspto-grants-2014_09
Patent number
US08822504B2

Reaction notes

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