2,3-Dihydroxybutanedioic 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 tartrate

HRID 69551Notes

Reaction equation

HRID 69551 reaction equation
[C:1]([OH:10])(=[O:9])[CH:2]([CH:4]([C:6]([OH:8])=[O:7])[OH:5])[OH:3].[F:11][C:12]([F:54])([F:53])[C:13]1[CH:14]=[C:15]([C:23]([CH3:52])([CH3:51])[C:24]([N:26]([CH3:50])[C:27]2[C:28]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=3[CH3:49])=[CH:29][C:30]([C@@H:33]3[NH:37][C@@:36]([CH3:41])([C:38]([NH2:40])=[O:39])[CH2:35][CH2:34]3)=[N:31][CH:32]=2)=[O:25])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1>CC(C)=O>[C:6]([CH:4]([CH:2]([C:1]([OH:10])=[O:9])[OH:3])[OH:5])([OH:8])=[O:7].[F:54][C:12]([F:11])([F:53])[C:13]1[CH:14]=[C:15]([C:23]([CH3:51])([CH3:52])[C:24]([N:26]([CH3:50])[C:27]2[C:28]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=3[CH3:49])=[CH:29][C:30]([C@@H:33]3[NH:37][C@@:36]([CH3:41])([C:38]([NH2:40])=[O:39])[CH2:35][CH2:34]3)=[N:31][CH:32]=2)=[O:25])[CH:16]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:18]=1

Participants

4

Reactant 2

HCID 8752,3-Dihydroxybutanedioic 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 86636100(5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide tartrate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

Acetone (7 ml) was added to tartaric acid (126.15 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). The resulting slurry was set up to temperature cycle (0-40° C.) whilst stirring at 500 rpm. After 1 hour, a thick, gel-like material had formed. Further acetone (13 ml) was then added in order to improve the mobility of the material. The reaction was temperature cycled for a further 3 days whilst stirring. The solid was then isolated and allowed to dry at 45° C. overnight to obtained the title compound in a crystalline form (463 mg). Onset melt 211° C. by DSC.

Workup

  1. dissolutionto dissolve the acid
  2. customwas set up to temperature cycle (0-40° C.)
  3. customa thick, gel-like material had formed
  4. waitcycled for a further 3 days
  5. stirringwhilst stirring
  6. customThe solid was then isolated
  7. customto dry at 45° C. overnight

Sources & evidence

ORD record
ord-f61dd536f89945a0b19ec3c90a142a61
Source dataset
uspto-grants-2014_09
Patent number
US08822504B2

Reaction notes

Loading…