Sodium hydride → HCID 68157559, compound

HRID 243277Notes

Reaction equation

HRID 243277 reaction equation
[N:1]1[C:9]([NH2:10])=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][CH:2]=1.[H-].[Na+].Br[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]=[CH:27][CH:28]=[CH:29][C:17]=2[N:16]=1>CN(C=O)C>[C:20]1([N:19]2[C:18]3[CH:26]=[CH:27][CH:28]=[CH:29][C:17]=3[N:16]=[C:15]2[CH2:14][N:5]2[CH:6]=[N:7][C:8]3[C:4]2=[N:3][CH:2]=[N:1][C:9]=3[NH2:10])[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68157796HCID 68157796, compoundHCID 178508693HCID 178508693, compound

Product 1

HCID 68157559HCID 68157559, compoundYield 6.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 9H-purin-6-ylamine (61 mg, 0.454 mmol) in DMF (1 mL) was added NaH (60% in mineral oil, 18 mg, 0.454 mmol) and the suspension was stirred at RT for 10 min under a nitrogen atmosphere. 2-Bromomethyl-1-phenyl-1H-benzoimidazole from Example 5 (0.454 mmol) in DMF (3 mL) was subsequently added and the reaction mixture was stirred at RT for 1 h. The crude reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated under reduced pressure. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM), then triturated with diethyl ether and purified by preparative HPLC (Phenomenex Gemini 5 μm C18 on a gradient 20-98% 0.1% HCO2H in acetonitrile/water). Crystallization from EtOAc/MeOH afforded 106 as a white solid (10 mg, 6%). LCMS: RT 3.47 min [M+H]+ 342.1. 1H NMR (CDCl3, 400 MHz): δ 8.21 (1H, s), 7.87 (1H, s), 7.84 (1H, d, J=8.01 Hz), 7.48-7.43 (3H, m), 7.36-7.20 (4H, m), 7.12 (1H, d, J=8.03 Hz), 5.57 (2H, s), 5.50 (2H, br)

Workup

  1. stirringthe reaction mixture was stirred at RT for 1 h
  2. customThe crude reaction mixture
  3. washwas washed with MeOH
  4. washthe product eluted with 2M NH3/MeOH
  5. additionThe product containing fractions
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)
  8. customtriturated with diethyl ether
  9. custompurified by preparative HPLC (Phenomenex Gemini 5 μm C18 on a gradient 20-98% 0.1% HCO2H in acetonitrile/water)
  10. customCrystallization from EtOAc/MeOH

Sources & evidence

ORD record
ord-b59e4516aabf4b92b04ddc6d90d589d7
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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