Hydrochloric Acid → 2-(4-ethoxybenzyl)-N-cyclohexyl-1-(cyclopropylmethyl)-N-methyl-1H-benzo[d]imidazole-5-carboxamide

HRID 1796478Notes

Reaction equation

HRID 1796478 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]([OH:16])=O)=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH3:26])=[CH:20][CH:19]=2)[CH2:3][CH2:2]1.CN(C(ON1N=N[C:37]2[CH:38]=[CH:39][CH:40]=[N:41][C:36]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:51][CH2:52]N(C(C)C)C(C)C.C1(CN)CCCCC1.Cl>CN(C=O)C.CCOC(C)=O.C(OCC)C>[CH:40]1([N:41]([CH3:36])[C:14]([C:12]2[CH:11]=[CH:10][C:9]3[N:5]([CH2:4][CH:1]4[CH2:3][CH2:2]4)[C:6]([CH2:17][C:18]4[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH3:26])=[CH:22][CH:23]=4)=[N:7][C:8]=3[CH:13]=2)=[O:16])[CH2:39][CH2:38][CH2:37][CH2:52][CH2:51]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 76688CyclohexanemethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22181336HCID 22181336, compound

Product 1

HCID 221813872-(4-ethoxybenzyl)-N-cyclohexyl-1-(cyclopropylmethyl)-N-methyl-1H-benzo[d]imidazole-5-carboxamideYield 91.5%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(Cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carboxylic acid (80 mg, 0.228 mmol) was dissolved in DMF (2 mL) and then HATU (104 mg, 0.274 mmol) was added followed by DIPEA (48 μL, 0.274 mmol). After stirring for 10 min; cyclohexylmethyl amine (0.456 mmol) was added and the resulting mixture was stirred overnight. The mixture was diluted with EtOAc (50 mL), washed with saturated NaHCO3 (2×10 mL) and then H2O (2×10 mL), dried over MgSO4, and concentrated to give a crude amide. The crude residue was purified by silica gel column chromatography to give pure product which was treated with 1 M HCl solution in diethyl ether to form a HCl salt as white solids (93 mg, 78%). 1H NMR (400 MHz, CD3OD): δ 7.66 (s, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.16 (d, J=8.6 Hz, 2H), 6.84 (d, J=8.6 Hz, 2H), 4.30 (s, 2H), 4.10–4.04 (m, 5H), 3.96 (q, J=7.6 Hz, 2H), 3.66–3.54 (m, 1H), 1.90–1.50 (m, 10H), 1.33 (t, J=7.6 Hz, 3H), 1.10–0.98 (m, 1H), 0.50–0.42 (m, 2H), 0.32–0.27 (m, 2H). MS (ESI) (M+H)+=446. Anal. Calcd for C28H35N3O2.2.2HCl: C, 63.96; H, 7.13; N, 7.99. Found: C, 64.11; H, 7.24; N, 7.73.

Workup

  1. stirringthe resulting mixture was stirred overnight
  2. washwashed with saturated NaHCO3 (2×10 mL)
  3. dry with materialH2O (2×10 mL), dried over MgSO4
  4. concentrationconcentrated
  5. customto give a crude amide
  6. customThe crude residue was purified by silica gel column chromatography
  7. customto give pure product which

Sources & evidence

ORD record
ord-1862c08c0c88430ca007a43e1bec649c
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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