p-Toluenesulfonic acid → HCID 67236687, compound

HRID 1028111Notes

Reaction equation

HRID 1028111 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]3)=[N:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl[C:25]1[N:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=1.CC1C=CC(S(O)(=O)=O)=CC=1.CN(C)C=O>O1CCOCC1.C(OCC)(=O)C>[F:32][C:31]([F:34])([F:33])[C:29]1[CH:28]=[CH:27][N:26]=[C:25]([NH:1][C:2]2[CH:3]=[C:4]([C:8]3[S:12][C:11]([N:13]4[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]4)=[N:10][CH:9]=3)[CH:5]=[CH:6][CH:7]=2)[N:30]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6228DimethylformamideHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 77231057HCID 77231057, compound

Product 1

HCID 67236687HCID 67236687, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of ethyl 1-[5-(3-aminophenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate (42 mg, 0.13 mmol) in dioxane (1.3 mL) was added 2-chloro-4-(trifluoromethyl)pyrimidine (23 mg, 1.3 mmol) and 4-methylbenzenesulfonic acid (24 mg, 0.127 mmol), resulting in the instant formation of a suspension. The mixture was heated to 100° C. and N,N-dimethylformamide (0.5 mL) was added to afford a homogenous mixture. The solution was heated at 100° C. for an additional 2 hours. Thus the mixture was the cooled to room temperature, diluted with ethyl acetate (30 mL), and washed with saturated aqueous sodium bicarbonate (30 mL) and brine (30 mL). The aqueous fractions were further extracted with ethyl acetate (30 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. Purification by CombiFlash (30-100% ethyl acetate:hexanes) provided 22 mg (0.046 mmol, 36% yield) of ethyl 1-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate as a white solid.

Workup

  1. customresulting in the instant formation of a suspension
  2. customto afford a homogenous mixture
  3. temperatureThe solution was heated at 100° C. for an additional 2 hours
  4. temperaturecooled to room temperature
  5. washwashed with saturated aqueous sodium bicarbonate (30 mL) and brine (30 mL)
  6. extractionThe aqueous fractions were further extracted with ethyl acetate (30 mL)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customPurification by CombiFlash (30-100% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-c4f2ca3baebc437c801986caca47e8b5
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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