p-Toluenesulfonic acid → Ethyl 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate

HRID 1028148Notes

Reaction equation

HRID 1028148 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([C:19]2[N:20]=[C:21]([N:24]3[CH2:29][CH2:28][CH:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:26][CH2:25]3)[S:22][CH:23]=2)[CH:16]=[CH:17][CH:18]=1.CC1C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[F:9][C:8]([F:11])([F:10])[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:12][C:13]2[CH:14]=[C:15]([C:19]3[N:20]=[C:21]([N:24]4[CH2:29][CH2:28][CH:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:26][CH2:25]4)[S:22][CH:23]=3)[CH:16]=[CH:17][CH:18]=2)[N:7]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 77231056Ethyl 1-[4-(3-aminophenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate

Product 1

HCID 71075072Ethyl 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-chloro-4-(trifluoromethyl)pyrimidine (42 mg, 0.23 mmol), ethyl 1-[4-(3-aminophenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate (76 mg, 0.23 mmol) and 4-methylbenzenesulfonic acid (44 mg, 0.23 mmol) in dioxane (1 mL) was heated to 100° C. overnight. After cooling to room temperature the reaction was concentrated under reduced pressure. The resulting residue was diluted with 30 mL ethyl acetate and washed with 30 mL saturated aqueous sodium bicarbonate and 30 mL brine. The aqueous layers were further extracted with 30 mL ethyl acetate. The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. Purification by CombiFlash (10-50% ethyl acetate/hexanes) provided 38 mg (0.08 mmol, 35% yield) of ethyl 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate as a white solid.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. additionThe resulting residue was diluted with 30 mL ethyl acetate
  3. washwashed with 30 mL saturated aqueous sodium bicarbonate and 30 mL brine
  4. extractionThe aqueous layers were further extracted with 30 mL ethyl acetate
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by CombiFlash (10-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-6cfa782dab1e4b0b848f29ed5206c2a6
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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