Hydrochloric Acid → 1-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxamide

HRID 1040169Notes

Reaction equation

HRID 1040169 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([C:30]#[N:31])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.[OH-:32].[Na+].Cl>>[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([C:30]([NH2:31])=[O:32])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 584561351-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarbonitrile

Product 1

HCID 584563021-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxamideYield 8.7%

Conditions

Temperature
100 °C

Procedure

A mixture of 1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarbonitrile (45 mg, 0.10 mmol) and NaOH (1M in MeOH, 0.5 ml, 0.50 mmol) was heated at 100° C. in the microwave for 16 hrs. The mixture was brought to pH=3 by addition of HCl (1.0 N in H2O) and then partitioned between EtOAc (5 mL) and brine (5 mL). The organic layer was separated, dried (Na2SO4), filtered and the volatiles were removed under reduced pressure. The residue was purified by HPLC (gradient elution 40% to 100% CH3CN in H2O/0.1% TFA, 20 mins, 20 ml/min) to give the title compound (4.0 mg, 8.67 μmol, 8.5% yield) as a white solid.

Workup

  1. custompartitioned between EtOAc (5 mL) and brine (5 mL)
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe volatiles were removed under reduced pressure
  6. customThe residue was purified by HPLC (gradient elution 40% to 100% CH3CN in H2O/0.1% TFA, 20 mins, 20 ml/min)

Sources & evidence

ORD record
ord-185887d8fa5144f9a5578bc0a3b93dba
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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