Potassium Phosphate, Tribasic → HCID 178437593, compound

HRID 1482892Notes

Reaction equation

HRID 1482892 reaction equation
Cl[C:2]1[CH:3]=[N:4][C:5]([C:8]([C@H:10]2[CH2:15][CH2:14][C@H:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]2)=[CH2:9])=[N:6][CH:7]=1.[F:20][CH:21]([F:45])[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]2[CH:34]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:32]=[C:31]([CH3:44])[CH:30]=2)[N:23]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Cl-].[Na+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:45][CH:21]([F:20])[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]2[CH:34]=[C:33]([C:2]3[CH:3]=[N:4][C:5]([C:8]([C@H:10]4[CH2:15][CH2:14][C@H:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]4)=[CH2:9])=[N:6][CH:7]=3)[CH:32]=[C:31]([CH3:44])[CH:30]=2)[N:23]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 584561714-(difluoromethyl)-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amineHCID 178437632HCID 178437632, compound

Product 1

HCID 178437593HCID 178437593, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of methyl trans-4-[1-(5-chloropyrimidin-2-yl)ethenyl]cyclohexanecarboxylate (8 mg, 0.028 mmol), 4-(difluoromethyl)-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (10.3 mg, 0.028 mmol), tris(dibenzylideneacetone)-dipalladium(0) (1.3 mg, 1.42 μmol), XPhos (1.36 mg, 2.85 μmol) and potassium phosphate tribasic (18 mg, 0.085 mmol) in 1,4-dioxane (2 mL) and water (0.5 mL) was stirred at 110° C. under a nitrogen atmosphere for 3 hours. After cooling to room temperature, the mixture was diluted with brine and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to afford methyl trans-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethenyl}cyclohexanecarboxylate. MS ESI calc'd for C26H28F2N5O2 [M+H]+ 480. found 480. 1H NMR: (400 MHz, CDCl3) δ 8.94 (s, 2H), 8.72 (d, J=4.8 Hz, 1H), 8.62 (d, J=5.2 Hz, 1H), 7.88 (s, 1H), 7.37 (s, 1H), 7.13-7.11 (m, 1H), 7.04-7.03 (m, 1H), 6.43 (s, 1H), 5.48 (s, 1H), 3.69 (s, 3H), 3.09-3.06 (m, 1H), 2.46 (s, 3H), 2.05-2.02 (m, 3H), 1.69-1.62 (m, 3H), 1.39-1.33 (m, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-e411ffe44fb24c60a746be91048831f8
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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