1-Hydroxybenzotriazole → N-(1-cyclohexyl-5-piperidin-1-ylmethyl-1H-benzimidazol-2-yl)-3-(1-tetrazolyl) benzamide

HRID 1868622Notes

Reaction equation

HRID 1868622 reaction equation
[CH:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([CH2:16][N:17]4[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]4)=[CH:15][C:10]=3[N:9]=[C:8]2[NH2:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:24]1([C:29]2[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=2)[C:32](O)=[O:33])[CH:28]=[N:27][N:26]=[N:25]1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=N>CN(C)C=O.O>[CH:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([CH2:16][N:17]4[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]4)=[CH:15][C:10]=3[N:9]=[C:8]2[NH:23][C:32](=[O:33])[C:31]2[CH:35]=[CH:36][CH:37]=[C:29]([N:24]3[CH:28]=[N:27][N:26]=[N:25]3)[CH:30]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 7502203-(1H-tetrazol-1-yl)benzoic acidHCID 218991781-Cyclohexyl-5-[(piperidin-1-yl)methyl]-1H-benzimidazol-2-amineHCID 21899179Dimethylaminopropyl carbodiimide hydrochloride

Product 1

HCID 21899125N-(1-cyclohexyl-5-piperidin-1-ylmethyl-1H-benzimidazol-2-yl)-3-(1-tetrazolyl) benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1-cyclohexyl-5-piperidin-1-ylmethyl-1H-benzimidazol-2-amine (100 mg, 0.32 mmol, prepared above) and 3-(1-tetrazolyl)-benzoic acid (76 mg, 0.40 mmol) in N,N-dimethylformamide (2 mL) was added 1-hydroxybenzotriazole (57 mg, 0.42 mmol) followed by 1-(3-dimethylaminopropyl)carbodiimide hydrochloride (80 mg, 0.42 mmol). N,N-diisoproplethylamine (100 mg, 0.77 mmol) was then added and the solution was allowed to stir at room temperature. After 18 hr, the reaction mixture was diluted with N,N-dimethylformamide (2 mL) and water (1 mL), filtered, and purified without work-up by preparative scale HPLC. Freeze-drying afforded (N-(1-cyclohexyl-5-piperidin-1-ylmethyl-1H-benzimidazol-2-yl)-3-(1-tetrazolyl) benzamide) as a cream solid (27 mg, 0.056 mmol): 1H NMR (DMSO-d6, 300 MHz) δ 10.20 (s, 1H), 9.30 (broad s, 1H), 8.63 (s, 1H), 8.34 (d, J=10.0 Hz, 1H), 8.02 (d, J=10 Hz, 1H), 7.81-7.64 (m, 2H), 7.64 (s, 1H), 7.33 (d, J=10.0 Hz, 1H), 4.83-4.63 (m, 1H), 4.41-4.29 (m, 2H), 2.99-1.33 (m, 18H). MS: API m/z 485 (M+H+)

Workup

  1. additionN,N-diisoproplethylamine (100 mg, 0.77 mmol) was then added
  2. filtrationfiltered
  3. custompurified without work-up by preparative scale HPLC
  4. customFreeze-drying

Sources & evidence

ORD record
ord-8d444efe0b4346e089c4bcfc07c68400
Source dataset
uspto-grants-2009_12
Patent number
US07635774B2

Reaction notes

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