Acetonitrile → 1-[4-(Methylamino)-6-(2-methylphenyl)-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide

HRID 1678433Notes

Reaction equation

HRID 1678433 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])=[O:17])[CH2:12][CH2:11]2)[N:3]=1.[CH3:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].CC#N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:9][NH:8][C:6]1[N:7]=[C:2]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[CH3:30])[N:3]=[C:4]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:28])([F:29])[F:27])=[O:17])[CH2:12][CH2:11]2)[N:5]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 866443121-[4-chloro-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide2×

Product 1

HCID 594477291-[4-(Methylamino)-6-(2-methylphenyl)-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamideYield 30.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 1-[4-chloro-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide (Intermediate 7d, 75 mg, 0.17 mmol, 1.0 equiv), (2-methylphenyl)boronic acid (29 mg, 0.21 mmol, 1.2 equiv), and Na2CO3 (37 mg, 0.35 mmol, 2.0 equiv) in 3:1 CH3CN:H2O was added Pd(PPh3)4 (10 mg, 0.0088 mmol, 0.05 equiv). The reaction mixture was heated at 90° C. for 1 h. The resulting suspension was filtered through an SCX resin (55 □m, 70 A, 2 g/12 mL giga tubes) using MeOH, and the product was recovered by eluting with 2.0 M NH3 in MeOH. The filtrate was concentrated, and the resulting residue was purified using reverse-phase HPLC (XBridge, 10-80% CH3CN/H2O, 0.1% TFA, 12 min) to afford 25 mg (30%) of the title compound. MS (ES+): m/e 485.2 [M+H]+.

Workup

  1. filtrationThe resulting suspension was filtered through an SCX resin (55 □m, 70 A, 2 g/12 mL giga tubes)
  2. customthe product was recovered
  3. washby eluting with 2.0 M NH3 in MeOH
  4. concentrationThe filtrate was concentrated
  5. customthe resulting residue was purified
  6. customreverse-phase HPLC (XBridge, 10-80% CH3CN/H2O, 0.1% TFA, 12 min)

Sources & evidence

ORD record
ord-0421acd43f134a4f9921160e5285d9f0
Source dataset
uspto-grants-2011_08
Patent number
US08008483B2

Reaction notes

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