Sodium hydride → 9-(6-fluoro-1-phenyl-1H-benzoimidazol-2-ylmethyl)-9H-purin-6-ylamine

HRID 243456Notes

Reaction equation

HRID 243456 reaction equation
[H-].[Na+].[N:3]1[C:11]([NH2:12])=[C:10]2[C:6]([NH:7][CH:8]=[N:9]2)=[N:5][CH:4]=1.Cl[CH2:14][C:15]1[N:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:18]2[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:17]=2[N:16]=1>CN(C=O)C>[F:30][C:27]1[CH:28]=[CH:29][C:17]2[N:16]=[C:15]([CH2:14][N:7]3[CH:8]=[N:9][C:10]4[C:6]3=[N:5][CH:4]=[N:3][C:11]=4[NH2:12])[N:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:18]=2[CH:26]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 623773732-(chloromethyl)-6-fluoro-1-phenyl-1H-1,3-benzodiazoleHCID 178508693HCID 178508693, compound

Product 1

HCID 681573209-(6-fluoro-1-phenyl-1H-benzoimidazol-2-ylmethyl)-9H-purin-6-ylamine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

Sodium hydride, NaH (60% in mineral oil, 23 mg, 0.69 mmol) was added to a suspension of 9H-purin-6-ylamine (93 mg, 0.69 mmol) in DMF (1 mL) under a nitrogen atmosphere. The reaction mixture was stirred for 15 min then 2-chloromethyl-6-fluoro-1-phenyl-1H-benzoimidazole (148 mg, 0.57 mmol) in DMF (1 mL) added. After 30 min stirring at RT, the temperature was increased to 70° C. and stirring continued for 3 h. The volatiles were removed under reduced pressure and the resulting residue partitioned between DCM and water. The aqueous phase was extracted with DCM (×3) and the combined organic fractions dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2N NH3/MeOH in DCM) to afford still impure 9-(6-fluoro-1-phenyl-1H-benzoimidazol-2-ylmethyl)-9H-purin-6-ylamine. Impure 9-(6-fluoro-1-phenyl-1H-benzoimidazol-2-ylmethyl)-9H-purin-6-ylamine was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a gradient 20-98%, 0.1% HCO2H in acetonitrile/water) to afford pure 376 as a white solid (45 mg, 22%). LCMS (Method K): RT 3.18 min [M+H]+ 360.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.06 (1H, s), 8.04 (1H, s), 7.68-7.55 (6H, m), 7.21 (2H, br s), 7.15-7.08 (1H, m), 6.97 (1H, dd, J=8.98, 2.55 Hz), 5.58 (2H, s)

Workup

  1. stirringAfter 30 min stirring at RT
  2. stirringstirring
  3. waitcontinued for 3 h
  4. customThe volatiles were removed under reduced pressure
  5. customthe resulting residue partitioned between DCM and water
  6. extractionThe aqueous phase was extracted with DCM (×3)
  7. dry with materialthe combined organic fractions dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2N NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-fb68975756c84993907da89ad358e89d
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…