Cesium carbonate → 5-{1-tert-Butyl-2-[2-(2,4-dimethyl-oxazol-5-yl)-phenyl]-1H-benzimidazol-5-yl}-pyrimidin-2-ylamine

HRID 1966752

Reaction equation

HRID 1966752 reaction equation
[C:1]([N:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]3[CH:15]=[N:16][C:17]([NH2:20])=[N:18][CH:19]=3)=[CH:13][C:8]=2[N:7]=[C:6]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1I)([CH3:4])([CH3:3])[CH3:2].[CH3:28][C:29]1[O:30][CH:31]=[C:32]([CH3:34])[N:33]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([N:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]3[CH:15]=[N:16][C:17]([NH2:20])=[N:18][CH:19]=3)=[CH:13][C:8]=2[N:7]=[C:6]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:31]1[O:30][C:29]([CH3:28])=[N:33][C:32]=1[CH3:34])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 1389612,4-DimethyloxazoleHCID 585420695-[1-tert-butyl-2-(2-iodo-phenyl)-1H-benzimidazol-5-yl]-pyrimidin-2-ylamine

Product 1

HCID 585419305-{1-tert-Butyl-2-[2-(2,4-dimethyl-oxazol-5-yl)-phenyl]-1H-benzimidazol-5-yl}-pyrimidin-2-ylamineYield 41%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
140 °C

Procedure

To a vial are added 5-[1-tert-butyl-2-(2-iodo-phenyl)-1H-benzimidazol-5-yl]-pyrimidin-2-ylamine (50 mg, 0.107 mmol), 2,4-dimethyl-oxazole (21 mg, 0.216 mol), palladium(II) acetate (5 mg, 0.022 mmol), PPh3 (6 mg, 0.023 mmol) and Cs2CO3 (70 mg, 0.215 mmol) in DMF (1.5 mL). The reaction mixture is stirred at 140° C. for 18 hours. The reaction mixture is diluted with EtOAc/water. The organic layer is separated, washed with brine, dried under anhydrous Na2SO4, filtered and concentrated. The residue is purified by silica gel flash column chromatography with 0-5% MeOH/CH2Cl2 as the eluent. The product fractions are collected and concentrated to afford the title compound (19 mg, 41%) as an off-white solid. LCMS (ESMS): m/z 439.86 (M++1)

Workup

  1. customThe organic layer is separated
  2. washwashed with brine
  3. customdried under anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by silica gel flash column chromatography with 0-5% MeOH/CH2Cl2 as the eluent
  7. customThe product fractions are collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c897844a27c649219e060d5138cf8e00
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Linked notes

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