Methanol → 2-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-2-(7H-purin-6-ylamino)-ethanol

HRID 243351Notes

Reaction equation

HRID 243351 reaction equation
C([O:8][CH2:9][C@H:10]([NH:27][C:28]1[N:36]=[CH:35][N:34]=[C:33]2[C:29]=1[NH:30][CH:31]=[N:32]2)[C:11]1[N:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:14]2[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:13]=2[N:12]=1)C1C=CC=CC=1.B(Br)(Br)Br.CO>C(Cl)Cl>[F:26][C:23]1[CH:24]=[CH:25][C:13]2[N:12]=[C:11]([CH:10]([NH:27][C:28]3[N:36]=[CH:35][N:34]=[C:33]4[C:29]=3[NH:30][CH:31]=[N:32]4)[CH2:9][OH:8])[N:15]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:14]=2[CH:22]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromide2×HCID 68157727[(R)-2-Benzyloxy-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-(7H-purin-6-yl)amine

Product 1

HCID 601621642-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-2-(7H-purin-6-ylamino)-ethanolYield 59.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [(R)-2-benzyloxy-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-(7H-purin-6-yl)amine (124 mg, 0.26 mmol) in anhydrous DCM (3 mL) at 0° C. under a nitrogen atmosphere was added boron tribromide (1.0M in DCM, 0.3 mL, 0.26 mmol) dropwise. The reaction mixture was slowly warmed to RT and stirred at RT for 1 h. Additional BBr3 (0.3 mL) was added and stirring continued for 1 h. MeOH was added then the volatiles removed under reduced pressure. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) to afford 172 (60 mg, 59%). LCMS (Method K): RT 3.11 min [M+H]+ 390.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.93 (0.8H, s), 12.17 (0.2H, s), 8.27-8.01 (2H, m), 7.74-7.43 (6H, m), 7.16-7.01 (1H, m), 6.93-6.79 (1H, m), 5.56-5.31 (1H, m), 5.21-5.02 (1H, m), 3.95-3.74 (2H, m). Signals split due to presence of rotamers/tautomers

Workup

  1. stirringstirring
  2. waitcontinued for 1 h
  3. customthe volatiles removed under reduced pressure
  4. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-dcb7a755d2ff4ad6be77f6f855a4a718
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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