2-(Dicyclohexylphosphino)biphenyl → 4-((Cyclopropylmethoxy)methyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

HRID 59146Notes

Reaction equation

HRID 59146 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][O:9][CH2:10][CH:11]2[CH2:13][CH2:12]2)[CH:5]=[C:4]([CH2:14][O:15][CH2:16][C:17]([F:20])([F:19])[F:18])[N:3]=1.[CH3:21][O:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[N:30]1[CH:34]=[C:33]([CH3:35])[N:32]=[CH:31]1)[NH2:26].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH:11]1([CH2:10][O:9][CH2:8][C:6]2[CH:5]=[C:4]([CH2:14][O:15][CH2:16][C:17]([F:20])([F:19])[F:18])[N:3]=[C:2]([NH:26][C:25]3[CH:27]=[CH:28][C:29]([N:30]4[CH:34]=[C:33]([CH3:35])[N:32]=[CH:31]4)=[C:23]([O:22][CH3:21])[CH:24]=3)[N:7]=2)[CH2:13][CH2:12]1

Participants

6

Reactant 3

HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)anilineHCID 117821330HCID 117821330, compound

Product 1

HCID 863438944-((Cyclopropylmethoxy)methyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

2-Chloro-4-((cyclopropylmethoxy)methyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (approximately 50% pure, 33 mg, 0.11 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (26 mg, 0.13 mmol), palladium (II) acetate (4 mg, 0.02 mmol), 2-(dicyclohexylphosphino)-biphenyl (6 mg, 0.02 mmol) cesium carbonate (69 mg, 0.21 mmol) and dioxane (2 mL) were mixed in a vial. The vial was capped, evacuated and flushed with nitrogen. The mixture was heated by microwave irradiation at 120° C. for 1.5 h. The mixture was filtered through a pad of silica, the pad was washed with 10% methanol in ethyl acetate. The solvents were evaporated and the residue was purified by preparative HPLC to give the title compound as a dry film, 15 mg (28%).

Workup

  1. customThe vial was capped
  2. customevacuated
  3. customflushed with nitrogen
  4. filtrationThe mixture was filtered through a pad of silica
  5. washthe pad was washed with 10% methanol in ethyl acetate
  6. customThe solvents were evaporated
  7. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-21d6e830dfa845ddb2ce942f4c643352
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

Loading…