Sodium Carbonate → HCID 57829820, compound

HRID 1855539Notes

Reaction equation

HRID 1855539 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+].[CH3:32][O:33][C:34]1[CH:35]=[C:36]([NH2:46])[CH:37]=[CH:38][C:39]=1[N:40]1[CH:44]=[C:43]([CH3:45])[N:42]=[CH:41]1.[C:47]([C:51]1[CH:52]=[C:53]([NH:57][C:58]2[C:63]([F:64])=[CH:62][N:61]=[C:60](Cl)[N:59]=2)[N:54]([CH3:56])[N:55]=1)([CH3:50])([CH3:49])[CH3:48].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:47]([C:51]1[CH:52]=[C:53]([NH:57][C:58]2[C:63]([F:64])=[CH:62][N:61]=[C:60]([NH:46][C:36]3[CH:37]=[CH:38][C:39]([N:40]4[CH:44]=[C:43]([CH3:45])[N:42]=[CH:41]4)=[C:34]([O:33][CH3:32])[CH:35]=3)[N:59]=2)[N:54]([CH3:56])[N:55]=1)([CH3:50])([CH3:48])[CH3:49]

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenyl2×HCID 23676156Sodium t-butoxideHCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)anilineHCID 86633642HCID 86633642, compound2×

Product 1

HCID 57829820HCID 57829820, compoundYield 30.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Palladium(II) acetate (5.4 mg, 0.024 mmol) and 2-(dicyclohexylphosphino)biphenyl (17 mg, 0.048 mmol) were stirred in dioxane (2.7 mL) for 10 minutes at 20° C. under an atmosphere of nitrogen. Sodium tert.-butoxide (44 mg, 0.45 mmol), 3-methoxy-4-(4-methyl-imidazole-1-yl)-phenylamine (61 mg, 0.30 mmol) and (5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-(2-chloro-5-fluoro-pyrimidin-4-yl)-amine (94 mg, 0.33 mmol, WO2008099210) were added. The reaction was heated for 30 minutes to 200° C. in a microwave oven. Palladium(II) acetate (5.4 mg, 0.024 mmol), 2-(dicyclohexylphosphino)-biphenyl (17 mg, 0.048 mmol), sodium carbonate (48 mg, 0.45 mmol), (5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-(2-chloro-5-fluoro-pyrimidin-4-yl)-amine (85 mg, 0.3 mmol) and dioxane (1 mL) were added. The reaction was heated again for 30 minutes to 200° C. in a microwave oven. Water was added to the cooled reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using dichloromethane and then dichloromethane/methanol (19:1 v/v) as eluent to yield the title compound as a yellow solid (41 mg, 30%). MS ISP (m/e): 451.2 (100) [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=8.02 (s, 1H), 7.60 (s, 1H), 7.30 (s, 1H), 7.09 (d, 1H), 7.03 (m, 2H), 6.82 (s, 1H), 6.45 (br s, 1H, NH), 6.11 (s, 1H), 3.73 (s, 3H), 3.72 (s, 3H), 2.29 (s, 3H), 1.32 (s, 9H).

Workup

  1. temperatureThe reaction was heated for 30 minutes to 200° C. in a microwave oven
  2. temperatureThe reaction was heated again for 30 minutes to 200° C. in a microwave oven
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-3c3b932de4504b76b3b29d10693ccf7f
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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