2-Aminopurine → 9-[(6-Fluoro-1-phenyl-benzimidazol-2-yl)methyl]purin-2-amine

HRID 243453

Reaction equation

HRID 243453 reaction equation
[N:1]1[CH:9]=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][C:2]=1[NH2:10].[H-].[Na+].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:5]3[CH:6]=[N:7][C:8]4[C:4]3=[N:3][C:2]([NH2:10])=[N:1][CH:9]=4)[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 99552-AminopurineHCID 24758Sodium hydrideHCID 623773732-(chloromethyl)-6-fluoro-1-phenyl-1H-1,3-benzodiazole

Product 1

HCID 681580049-[(6-Fluoro-1-phenyl-benzimidazol-2-yl)methyl]purin-2-amineYield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred mixture of 9H-purin-2-ylamine (93 mg, 0.69 mmol) in DMF (1 mL) at RT and under a nitrogen atmosphere was added NaH (60% in mineral oil, 23 mg, 0.69 mmol). After 5 min, 2-chloromethyl-6-fluoro-1-phenyl-1H-benzoimidazole (150 mg, 0.575 mmol) in DMF (1 mL) was added. Stirring was continued for 18 h at RT. The crude reaction mixture was loaded onto an Isolute® SCX-2 cartridge and washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) to afford 372 as a white solid (96 mg, 47%). LCMS (Method K): RT 3.17 min [M+H]+360.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.56 (1H, s), 8.00 (1H, s), 7.70-7.57 (6H, m), 7.16-7.07 (1H, m), 6.97 (1H, dd, J=8.93, 2.50 Hz), 6.43 (2H, s), 5.48 (2H, s)

Workup

  1. waitwas continued for 18 h at RT
  2. customThe crude reaction mixture
  3. washwashed with MeOH
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-92dc46f5ce4f4722b52a79b6614dcca7
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Linked notes

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