Water → (4-Benzyl-6-methyl-pyrimidin-2-yl)-[4-(2-methyl-oxazol-5-yl)-phenyl]-amine

HRID 1855502Notes

Reaction equation

HRID 1855502 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH3:26][C:27]1[O:28][C:29]([C:32]2[CH:37]=[CH:36][C:35]([NH2:38])=[CH:34][CH:33]=2)=[CH:30][N:31]=1.[CH2:39]([C:46]1[CH:51]=[C:50]([CH3:52])[N:49]=[C:48](Cl)[N:47]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.O>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:39]([C:46]1[CH:51]=[C:50]([CH3:52])[N:49]=[C:48]([NH:38][C:35]2[CH:36]=[CH:37][C:32]([C:29]3[O:28][C:27]([CH3:26])=[N:31][CH:30]=3)=[CH:33][CH:34]=2)[N:47]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

7

Reactant 4

HCID 962WaterHCID 15187744-(2-Methyl-1,3-oxazol-5-yl)anilineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 866336184-Benzyl-2-chloro-6-methyl-pyrimidine

Product 1

HCID 57829785(4-Benzyl-6-methyl-pyrimidin-2-yl)-[4-(2-methyl-oxazol-5-yl)-phenyl]-amineYield 61%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

Palladium(II) acetate (9.3 mg, 0.041 mmol) and 2-(dicyclohexylphosphino)biphenyl (30 mg, 0.083 mmol) were stirred in dioxane (1.5 mL) for 15 minutes at room temperature under an atmosphere of nitrogen. Sodium tert.-butylate (76 mg, 0.78 mmol), 4-(2-methyl-oxazol-5-yl)phenylamine (90 mg, 0.52 mmol, CAS 89260-50-4) dissolved in dioxane (0.7 mL) and 4-benzyl-2-chloro-6-methyl-pyrimidine (124 mg, 0.57 mmol) were added. The reaction was heated for 30 minutes to 200° C. in a microwave oven. Water was added and the reaction was extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using dichloromethane and then methylenechloride/methanol (19:1 v/v) as eluent to yield the title compound as a yellow solid (112 mg, 61%). MS ISP (m/e): 357.2 (100) [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.69 (d, 2H), 7.53 (d, 2H), 7.26-7.35 (m, 4H), 7.11-7.12 (m, 2H), 6.45 (s, 1H), 3.97 (s, 2H), 2.52 (s, 3H), 2.36 (s, 3H).

Workup

  1. temperatureThe reaction was heated for 30 minutes to 200° C. in a microwave oven
  2. extractionthe reaction was extracted twice with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-94015e8198e94fa9a4c5d70fc73f4989
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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