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Hydrochloric Acid → [1-(7-Cyclopropyl-6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-(9H-purin-6-yl)-amine

HRID 243370
Notes
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Reaction equation

HRID 243370 reaction equation
[CH:1]1([C:4]2[C:9]3[N:10]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:11]([C@@H:13]([NH:15][C:16]4[N:24]=[CH:23][N:22]=[C:21]5[C:17]=4[N:18]=[CH:19][N:20]5C4CCCCO4)[CH3:14])=[N:12][C:8]=3[CH:7]=[CH:6][C:5]=2[F:37])[CH2:3][CH2:2]1.Cl>CO.O1CCOCC1>[CH:1]1([C:4]2[C:9]3[N:10]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:11]([CH:13]([NH:15][C:16]4[N:24]=[CH:23][N:22]=[C:21]5[C:17]=4[N:18]=[CH:19][NH:20]5)[CH3:14])=[N:12][C:8]=3[CH:7]=[CH:6][C:5]=2[F:37])[CH2:3][CH2:2]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 68158162[(S)-1-(7-Cyclopropyl-6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine

Product 1

HCID 178463569[1-(7-Cyclopropyl-6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-(9H-purin-6-yl)-amineYield 48.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent
HCID 31275
1,4-Dioxane
Solvent

Procedure

To a mixture of [(S)-1-(7-cyclopropyl-6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine (20 mg, 0.04 mmol) in MeOH (2 mL) was added 4N HCl in dioxane (0.25 mL) and the reaction mixture stirred at RT for 30 min. The volatiles were removed under reduced pressure and the resulting residue purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 10-90%, 0.1% HCO2H in acetonitrile/water) to afford 198 (8 mg, 48%). LCMS (Method K): RT 3.74 and 3.81 min [M+H]+ 414.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.89 (1H, br s), 8.19-7.97 (2H, m), 7.90-7.30 (7H, m), 7.04-6.95 (1H, dd, J=11.67, 8.76 Hz), 5.29 (1H, br s), 1.52 (3H, d, J=6.81 Hz), 1.28-1.18 (1H, m), 0.43-0.29 (2H, m), 0.25-0.08 (2H, m)

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe resulting residue purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 10-90%, 0.1% HCO2H in acetonitrile/water)

Sources & evidence

ORD record
ord-46ea6fefc83447c691df466030671e7f
Source dataset
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08653089B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes