Potassium Carbonate → HCID 67239865, compound

HRID 1028134Notes

Reaction equation

HRID 1028134 reaction equation
Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]([C:18]2[S:22][C:21]([N:23]3[CH2:29][CH2:28][CH2:27][NH:26][C:25](=[O:30])[CH2:24]3)=[N:20][CH:19]=2)[CH:14]=[C:15]([CH3:17])[CH:16]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>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]>[CH3:17][C:15]1[CH:14]=[C:13]([C:18]2[S:22][C:21]([N:23]3[CH2:29][CH2:28][CH2:27][NH:26][C:25](=[O:30])[CH2:24]3)=[N:20][CH:19]=2)[CH:12]=[C:11]([NH:10][C:2]2[N:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][N:3]=2)[CH:16]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 164271482-Chloro-4-(methylthio)pyrimidineHCID 67236328HCID 67236328, compound

Product 1

HCID 67239865HCID 67239865, compoundYield 56.2%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

To an oven-dried vial was added 2-chloro-4-methylthiopyrimidine (0.885 g, 4.13 mmol), intermediate XX (1.25 g, 4.13 mmol), tris-(dibenzylideneacetone)dipalladium(0) (0.379 g, 0.413 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.985 g, 2.067 mmol), and potassium carbonate (1.143 g, 8.27 mmol). The vial was evacuated and backfilled with Ar (g) 3×. Degassed t-amyl alcohol (13.78 mL) was added, and the mixture was sealed and heated to 90° C. overnight. After cooling to room temperature, diluted with methanol, added 10 g silica, and concentrated in vacuo. Purified by CombiFlash (100:0 to 0:20 dichloromethane:methanol) to afford 4-[5-(3-methyl-5-{[4-(methylsulfanyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (0.990 g, 2.321 mmol, 56% yield) as a yellow solid. MS APCI: [M+H]+ m/z 427.1. rhSYK activity=+++.

Workup

  1. customThe vial was evacuated
  2. additionDegassed t-amyl alcohol (13.78 mL) was added
  3. customthe mixture was sealed
  4. temperatureAfter cooling to room temperature
  5. additiondiluted with methanol
  6. additionadded 10 g silica
  7. concentrationconcentrated in vacuo
  8. customPurified by CombiFlash (100:0 to 0:20 dichloromethane:methanol)

Sources & evidence

ORD record
ord-fe31d0bc8f764123b83deb29d3b37343
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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