Hydrochloric Acid → HCID 67248187, compound

HRID 410524Notes

Reaction equation

HRID 410524 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]([C:24]2[S:28][C:27]([CH:29]3[CH2:34][CH2:33][CH:32]([C:35]([O:37]CC)=[O:36])[CH2:31][CH2:30]3)=[N:26][CH:25]=2)[CH:10]=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:12]=1)=[O:5])[CH3:2].[Li+].[OH-].Cl>O1CCCC1.CO>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]([C:24]2[S:28][C:27]([CH:29]3[CH2:34][CH2:33][CH:32]([C:35]([OH:37])=[O:36])[CH2:31][CH2:30]3)=[N:26][CH:25]=2)[CH:10]=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:12]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 67431839HCID 67431839, compound

Product 1

HCID 67248187HCID 67248187, compoundYield 20.02%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of ethyl 4-[5-(3-[(ethylcarbamoyl)amino]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylate (2.030 g, 3.70 mmol) in tetrahydrofuran (13.45 mL) and methanol (5.045 mL) was added aqueous 1N LiOH (11.10 mL, 11.10 mmol). The resulting solution was stirred 2 h at room temperature and 2 h at 50° C. The reaction was cooled to ambient temperature and was then quenched with HCl (11.10 mL, 11.10 mmol) and then diluted with aqueous 25% NH4OAc (to pH=7). The mixture was extracted with 2-Me-THF. The combined organic fractions were washed with brine, dried (Na2SO4), and filtered. The solvent was evaporated under reduced pressure and the resultant residue was purified by column chromatography on silica gel (Combiflash, 0-100% ethanol in dichloromethane) to give a brown oil-solid. The residue was triturated in hot ethyl acetate. Diethyl ether was added and the product was isolated by filtration. The solid was dried to give 4-[5-(3-[(ethylcarbamoyl)amino]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid (396 mg, 0.741 mmol, 20.02% yield) as a mixture of the syn and anti diastereoisomers. MS APCI: [M+H]+ m/z 535.1.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. extractionThe mixture was extracted with 2-Me-THF
  3. washThe combined organic fractions were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customThe solvent was evaporated under reduced pressure
  7. customthe resultant residue was purified by column chromatography on silica gel (Combiflash, 0-100% ethanol in dichloromethane)
  8. customto give a brown oil-solid
  9. customThe residue was triturated in hot ethyl acetate
  10. additionDiethyl ether was added
  11. customthe product was isolated by filtration
  12. customThe solid was dried

Sources & evidence

ORD record
ord-0904b41e29154d1f88d7b03eb2709895
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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