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

HRID 410514Notes

Reaction equation

HRID 410514 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([C:34]([NH2:36])=[O:35])[CH2:33][CH2:32][C:27]4(OCC[O:28]4)[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.Cl>C1COCC1.C([O-])(O)=O.[Na+]>[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([C:34]([NH2:36])=[O:35])[CH2:25][CH2:26][C:27](=[O:28])[CH2:32][CH2:33]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 672577948-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carboxamide

Product 1

HCID 672560721-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-oxocyclohexanecarboxamideYield 74.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
23 °C

Procedure

To a suspension of 8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carboxamide (700 mg, 1.35 mmol) in anhydrous THF (2 ml) and was added concentrated HCl (5.53 ml, 67.4 mmol). The resulting dark yellow solution was stirred at 23° C. for 6 h. The mixture was diluted with saturated aqueous NaHCO3 (80 ml) and extracted with EtOAc (2×70 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude oil was triturated with hexanes and diethyl ether which afforded 1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-oxocyclohexanecarboxamide (683 mg, 1.01 mmol, 74.6%) as an tan solid. MS APCI: [M+H]+ m/z 476.1.

Workup

  1. extractionextracted with EtOAc (2×70 ml)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude oil was triturated with hexanes and diethyl ether which

Sources & evidence

ORD record
ord-30502c5dcc1b4b66a2f5b8fbdef0a903
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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