1-Methylethyl hydrogen sulfate → (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 isopropyl sulfate

HRID 1620399Notes

Reaction equation

HRID 1620399 reaction equation
[CH:1]([O:4][S:5](=[O:8])(=[O:7])[OH:6])([CH3:3])[CH3:2].[NH2:9][C@@H:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[C:25]([O:27][C@H:28]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=3[N:40]3[CH:44]=[CH:43][C:42]([CH3:45])=[N:41]3)[C:29]([F:32])([F:31])[F:30])[N:24]=[C:23]([NH2:46])[N:22]=2)=[CH:17][CH:16]=1)[C:11]([OH:13])=[O:12]>CC(O)C.CO>[CH:1]([O:4][S:5]([OH:8])(=[O:7])=[O:6])([CH3:3])[CH3:2].[NH2:9][C@@H:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[C:25]([O:27][C@H:28]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=3[N:40]3[CH:44]=[CH:43][C:42]([CH3:45])=[N:41]3)[C:29]([F:31])([F:32])[F:30])[N:24]=[C:23]([NH2:46])[N:22]=2)=[CH:17][CH:16]=1)[C:11]([OH:13])=[O:12]

Participants

5

Reactant 2

HCID 813271-Methylethyl hydrogen sulfateHCID 25025298Telotristat

Product 1

HCID 57331287(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 isopropyl sulfateYield 54%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
75 °C

Procedure

1.0N isopropyl sulfuric acid (0.19 mL, 1.04 eq) in IPA was added to a 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, 0.05M, 0.183 mmol) in MeOH and followed by evaporation of solvent to dry. After adding of 6.5 mL MeCN/IPA (3/1) and heating at 75° C., a clear solution was obtained. 2.0 mL solvent was evaporated and stirred overnight. The precipitate was collected by filtration. The cake was washed with heptane, dried at 45° C. under vacuum overnight to give 68 mg (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 isopropyl sulfate, (54% yield).

Workup

  1. customfollowed by evaporation of solvent
  2. customto dry
  3. additionAfter adding of 6.5 mL MeCN/IPA (3/1)
  4. customa clear solution was obtained
  5. custom2.0 mL solvent was evaporated
  6. filtrationThe precipitate was collected by filtration
  7. washThe cake was washed with heptane
  8. customdried at 45° C. under vacuum overnight

Sources & evidence

ORD record
ord-f9f41f5f5f64492eb8990f9e298592e3
Source dataset
uspto-grants-2014_07
Patent number
US08772483B2

Reaction notes

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