Cyclopropylamine → 2-[3-(2-Cyclopropylaminoethyl)phenyl]-1h-benzimidazole-4-carboxamide

HRID 736695Notes

Reaction equation

HRID 736695 reaction equation
O1CCO[CH:2]1[CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[NH:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:22]([NH2:24])=[O:23])[C:15]=3[N:14]=2)[CH:10]=[CH:11][CH:12]=1.[CH:25]1([NH2:28])[CH2:27][CH2:26]1.C([BH3-])#N.[Na+]>C(O)(=O)C.O.CS(C)=O.CO>[CH:25]1([NH:28][CH2:2][CH2:6][C:7]2[CH:8]=[C:9]([C:13]3[NH:17][C:16]4[CH:18]=[CH:19][CH:20]=[C:21]([C:22]([NH2:24])=[O:23])[C:15]=4[N:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH2:27][CH2:26]1

Participants

8

Reactant 3

HCID 69828CyclopropylamineHCID 5003444Sodium cyanoborohydrideHCID 685329682-(3-[1,3]dioxolan-2-ylmethylphenyl)-1H-benzimidazole-4-carboxamide

Product 1

HCID 167271802-[3-(2-Cyclopropylaminoethyl)phenyl]-1h-benzimidazole-4-carboxamide

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of EXAMPLE 10A (300 mg, 0.88 mmol) in acetic acid (10 mL) and water (20 mL) was heated at 70° C. for 20 hours. After cooling, the solution was concentrated to give a light yellow solid. To a solution of the crude aldehyde (80 mg) in dimethyl sulfoxide (2 mL) and methanol (3 mL) was added cyclopropylamine (60 μL) and the mixture stirred at ambient temperature for 1 hour. Sodium cyanoborohydride (54 mg, 0.86 mmol) was added and the mixture heated at 55° C. overnight. Volatiles were removed and the residue purified by HPLC (Zorbax, C-18, 250×2.54 column, Mobile phase A: 0.1% trifluoroacetic acid in water; B: 0.1% trifluoroacetic acid in acetonitrile; 0-100% gradient) to provide 8.8 mg of the title compound as a trifluoroacetate salt. To a solution of this salt in 1:1 methanol/dichloromethane (1 mL) was added 1M HCl in ether (3 mL). Concentration afforded the title compound as a hydrochloride salt. 1H NMR (CD3OD): δ 0.91-1.03 (m, 4H), 2.83-2.89 (m, 1H), 3.23-3.29 (m, 2H), 3.49-3.55 (m, 2H), 7.70-7.79 (m, 3H), 8.03-8.13 (m, 3H), 8.20 (s, 1H),

Workup

  1. temperatureAfter cooling
  2. concentrationthe solution was concentrated
  3. customto give a light yellow solid
  4. temperaturethe mixture heated at 55° C. overnight
  5. customVolatiles were removed
  6. customthe residue purified by HPLC (Zorbax, C-18, 250×2.54 column, Mobile phase A: 0.1% trifluoroacetic acid in water; B: 0.1% trifluoroacetic acid in acetonitrile; 0-100% gradient)

Sources & evidence

ORD record
ord-e401853e7bcd4303a21cd4a5420bdfbd
Source dataset
uspto-grants-2009_09
Patent number
US07595406B2

Reaction notes

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