Potassium Carbonate → 5-{1-tert-Butyl-2-[2-(1-methyl-1H-pyrazol-4-yl)-phenyl]-1H-benzimidazol-5-yl}-pyrimidin-2-ylamine

HRID 1966677Notes

Reaction equation

HRID 1966677 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:11]2[CH:17]=[CH:18][C:19]([C:21]3[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=3)=[CH:20][C:10]=2[N:9]=1.[CH3:28][N:29]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[N:30]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:13]([N:12]1[C:11]2[CH:17]=[CH:18][C:19]([C:21]3[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=3)=[CH:20][C:10]=2[N:9]=[C:8]1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:32]1[CH:31]=[N:30][N:29]([CH3:28])[CH:33]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 585419535-[2-(2-bromo-phenyl)-1-tert-butyl-1H-benzimidazol-5-yl]-pyrimidin-2-ylamine

Product 1

HCID 585419705-{1-tert-Butyl-2-[2-(1-methyl-1H-pyrazol-4-yl)-phenyl]-1H-benzimidazol-5-yl}-pyrimidin-2-ylamineYield 34%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-[2-(2-bromo-phenyl)-1-tert-butyl-1H-benzimidazol-5-yl]-pyrimidin-2-ylamine (70 mg, 0.17 mmol) in DMF (5 mL) and H2O (1 mL) are added 1-methylpyrazole-4-boronic acid pinacol ester (52 mg, 0.25 mmol), Pd(PPh3)4 (19 mg, 0.017 mmol) and K2CO3 (23 mg, 0.17 mmol) at room temperature. The solution is heated to 120° C. for 1 hour in a microwave reactor. The solution is cooled down and 3-mercaptopropyl-functionalized silica gel (500 mg) is added. The solution is stirred for 15 minutes and then filtered. The filtrate is washed with H2O (10 mL) and is extracted with EtOAc (3×15 mL). The combined organic layer is dried (MgSO4), filtered and concentrated. The residue is purified by silica gel flash chromatography eluting with 10% MeOH in CH2Cl2 to afford the title compound (24 mg, 34%) as a white solid. LCMS (ESMS): m/z 424.20 (M++1)

Workup

  1. temperatureThe solution is cooled down
  2. addition3-mercaptopropyl-functionalized silica gel (500 mg) is added
  3. filtrationfiltered
  4. washThe filtrate is washed with H2O (10 mL)
  5. extractionis extracted with EtOAc (3×15 mL)
  6. dry with materialThe combined organic layer is dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel flash chromatography
  10. washeluting with 10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-4808f7d8cc244fb1a7d3175ad589f0aa
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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