Isopropanol → (S)-2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoic acid dibesylate

HRID 1620397Notes

Reaction equation

HRID 1620397 reaction equation
[NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[C:17]([O:19][C@H:20]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=3[N:32]3[CH:36]=[CH:35][C:34]([CH3:37])=[N:33]3)[C:21]([F:24])([F:23])[F:22])[N:16]=[C:15]([NH2:38])[N:14]=2)=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].[C:39]1([S:45]([OH:48])(=[O:47])=[O:46])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.CC(O)C.CCCCCCC>CO>[S:45]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([OH:48])(=[O:47])=[O:46].[S:45]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([OH:48])(=[O:47])=[O:46].[NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[C:17]([O:19][C@H:20]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=3[N:32]3[CH:36]=[CH:35][C:34]([CH3:37])=[N:33]3)[C:21]([F:23])([F:24])[F:22])[N:16]=[C:15]([NH2:38])[N:14]=2)=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 7371Benzenesulfonic AcidHCID 8900HeptaneHCID 25025298Telotristat

Product 1

HCID 131731656(S)-2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoic acid dibesylateYield 85.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the solution of (S)-2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoic acid free base (3.66 mL, 0.05 M, 0.183 mmol) in MeOH was added 1.0N benzenesulfonic acid (0.56 mL, 3.0 equiv.) prepared from IPA. After the solvent was evaporated, 3.0 mL IPA was added to give a clear solution. After adding 4.0 mL heptane in the period of 5 min, the reaction mixture was stirred for 2 hours. The solid was filtered, washed with, dried overnight under vacuum at 45° C. to give 135 mg (85.5% yield) (S)-2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoic acid dibesylate as an off-white solid.

Workup

  1. customAfter the solvent was evaporated
  2. addition3.0 mL IPA was added
  3. customto give a clear solution
  4. filtrationThe solid was filtered
  5. washwashed with,
  6. customdried overnight under vacuum at 45° C.

Sources & evidence

ORD record
ord-337c205a55b54abd91c49d546fe79af7
Source dataset
uspto-grants-2014_07
Patent number
US08772483B2

Reaction notes

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