Potassium Carbonate → HCID 71075371, compound

HRID 1028133Notes

Reaction equation

HRID 1028133 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[C:5]([F:14])=[CH:4][N:3]=1.[NH2:15][C:16]1[CH:17]=[C:18]([C:23]2[S:27][C:26]([N:28]3[CH2:34][CH2:33][CH2:32][NH:31][C:30](=[O:35])[CH2:29]3)=[N:25][CH:24]=2)[CH:19]=[C:20]([CH3:22])[CH:21]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.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]>[F:14][C:5]1[C:6]([O:8][CH:9]2[CH2:13][CH2:12][O:11][CH2:10]2)=[N:7][C:2]([NH:15][C:16]2[CH:17]=[C:18]([C:23]3[S:27][C:26]([N:28]4[CH2:34][CH2:33][CH2:32][NH:31][C:30](=[O:35])[CH2:29]4)=[N:25][CH:24]=3)[CH:19]=[C:20]([CH3:22])[CH:21]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67236328HCID 67236328, compound2×HCID 79081625HCID 79081625, compound

Product 1

HCID 71075371HCID 71075371, compoundYield 71.9%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

2-Chloro-5-fluoro-4-(tetrahydrofuran-3-yloxy)pyrimidine (70 mg, 0.32 mol), 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 97 mg, 0.32 mmol), Pd2(dba)3 (29 mg, 0.032 mmol), XPhos (76 mg, 0.16 mmol) and potassium carbonate (89 mg, 0.64 mmol) were added to a flask. The flask was purged and flushed with argon (3×). Degassed tert-amyl alcohol (1.1 ml) was added, the reaction mixture was purged with nitrogen for 5 min, and then heated to 90° C. overnight. The mixture was cooled to room temperature, diluted with ethyl acetate, treated with water, and extracted with ethyl acetate (×3). The combined organics were washed with brine, dried over sodium sulfate, concentrated, and purified by Combiflash (methanol/dichloromethane eluant) to provide 109 mg (0.23 mmol, 70% yield) of 4-[5-(3-{[5-fluoro-4-(tetrahydrofuran-3-yloxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one. MS APCI: [M+H]+ m/z 485.1. 1H NMR (500 MHz, DMSO-d6) δ 9.53 (s, 1H), 8.30 (d, J=2.9 Hz, 1H), 7.59 (t, J=4.8 Hz, 1H), 7.57 (s, 1H), 7.48 (s, 1H), 7.34 (s, 1H), 6.95 (s, 1H), 5.64 (t, J=4.9 Hz, 1H), 4.16 (s, 2H), 3.97-3.73 (m, 6H), 3.21 (m, 2H), 2.32 (m, 1H), 2.26 (s, 3H), 2.10 (m, 1H), 1.77 (s, 2H). rhSyk=++

Workup

  1. customThe flask was purged
  2. customflushed with argon (3×)
  3. additionDegassed tert-amyl alcohol (1.1 ml) was added
  4. customthe reaction mixture was purged with nitrogen for 5 min
  5. temperatureThe mixture was cooled to room temperature
  6. additiondiluted with ethyl acetate
  7. additiontreated with water
  8. extractionextracted with ethyl acetate (×3)
  9. washThe combined organics were washed with brine
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated
  12. custompurified by Combiflash (methanol/dichloromethane eluant)

Sources & evidence

ORD record
ord-a191a93a88c74da2b96bdcde5ad7b51a
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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