Potassium Phosphate, Tribasic → 1-[4-(methylamino)-6-phenyl-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide

HRID 1678445Notes

Reaction equation

HRID 1678445 reaction equation
C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[C:20]1(B(O)O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl[C:30]1[N:35]=[C:34]([NH:36][CH3:37])[N:33]=[C:32]([N:38]2[CH2:43][CH2:42][CH:41]([C:44]([NH:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[C:54]([F:57])([F:56])[F:55])=[O:45])[CH2:40][CH2:39]2)[N:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:37][NH:36][C:34]1[N:35]=[C:30]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:31]=[C:32]([N:38]2[CH2:39][CH2:40][CH:41]([C:44]([NH:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[C:54]([F:57])([F:55])[F:56])=[O:45])[CH2:42][CH2:43]2)[N:33]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 75806TricyclohexylphosphineHCID 866443121-[4-chloro-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide

Product 1

HCID 252612871-[4-(methylamino)-6-phenyl-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A 5 ml microwave vial was charged with palladium (II) acetate (0.38 mg, 0.0017 mmol, 0.010 equiv), tricyclohexylphosphine (0.95 mg, 0.0034 mmol, 0.020 equiv), and phenyl boronic acid (30.9 mg, 0.253 mmol, 1.50 equiv). A premixed solution of 1,4-dioxane (0.875 ml) and 1-[4-chloro-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide was added, followed by a premixed solution of water (0.125 ml) and potassium phosphate tribasic (71.7 mg, 0.338 mmol, 2.00 equiv). The reaction was heated via a microwave reactor for 20 min at 150° C. The reaction was diluted with water (5 ml) and extracted three times with ethyl acetate (5 ml). The ethyl acetate extracts were combined, dried with Na2SO4, filtered, and concentrated under reduced pressure. The residue was dissolved in 1.5 ml DMSO and purified via reverse-phase HPLC purification to afford the title compound. MS (ES+): m/e 470.9 [M+H]+.

Workup

  1. extractionextracted three times with ethyl acetate (5 ml)
  2. dry with materialdried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in 1.5 ml DMSO
  6. custompurified via reverse-phase HPLC purification

Sources & evidence

ORD record
ord-1f94febe0b1d49859911127ccb3efda1
Source dataset
uspto-grants-2011_08
Patent number
US08008483B2

Reaction notes

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