Cesium carbonate → 4-(1-ethoxyvinyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-(methoxymethyl)pyrimidin-2-amine

HRID 59116Notes

Reaction equation

HRID 59116 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[CH2:9])[CH:5]=[C:4]([CH2:13][O:14][CH3:15])[N:3]=1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][C:24]=1[N:25]1[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26]1)[NH2:21].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:11]([O:10][C:8]([C:6]1[CH:5]=[C:4]([CH2:13][O:14][CH3:15])[N:3]=[C:2]([NH:21][C:20]2[CH:22]=[CH:23][C:24]([N:25]3[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26]3)=[C:18]([O:17][CH3:16])[CH:19]=2)[N:7]=1)=[CH2:9])[CH3:12]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)anilineHCID 1178209822-Chloro-4-(1-ethoxyvinyl)-6-(methoxymethyl)pyrimidine

Product 1

HCID 1178241374-(1-ethoxyvinyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-(methoxymethyl)pyrimidin-2-amineYield 52%

Reagents, catalysts & solvents 2

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

Procedure

2-Chloro-4-(1-ethoxyvinyl)-6-(methoxymethyl)pyrimidine (167 mg, 0.73 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (178 mg, 0.88 mmol), cesium carbonate (476 mg, 1.46 mmol), palladium acetate (25 mg, 0.11 mmol) and 2-(dicyclohexylphosphino)biphenyl (38 mg, 0.11 mmol) in dioxane (4 mL) was heated under argon at 120° C. for 90 minutes in a microwave reactor. The mixture was filtered through a short silica plug which was washed with 10% MeOH in EtOAc (75 mL). The solvent was evaporated and the residue was purified by preparative HPLC to give the title compound 150 mg (52%).

Workup

  1. filtrationThe mixture was filtered through a short silica plug which
  2. washwas washed with 10% MeOH in EtOAc (75 mL)
  3. customThe solvent was evaporated
  4. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-9a29361d11b74941bd41da043a744e7b
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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