Ethylamine → N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1-ethyl-1H-imidazol-2-yl)phenethoxy)propanamide

HRID 909940Notes

Reaction equation

HRID 909940 reaction equation
[CH2:1]([NH2:3])[CH3:2].[CH:4](=O)[CH:5]=O.C([O-])(=O)C.[NH4+:12].[CH:13]1([N:19]([CH2:35][CH:36]([O:39][CH3:40])[O:37][CH3:38])[C:20](=[O:34])[CH2:21][CH2:22][O:23][CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([CH:32]=O)[CH:27]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>CO.C(Cl)Cl>[CH:13]1([N:19]([CH2:35][CH:36]([O:39][CH3:40])[O:37][CH3:38])[C:20](=[O:34])[CH2:21][CH2:22][O:23][CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]3[N:3]([CH2:4][CH3:5])[CH:1]=[CH:2][N:12]=3)[CH:27]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 6341EthylamineHCID 7860GlyoxalHCID 517165Ammonium AcetateHCID 59290390N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-formylphenethoxy)propanamide

Product 1

HCID 59290485N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1-ethyl-1H-imidazol-2-yl)phenethoxy)propanamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Ethylamine (70% in water, 0.526 mL), followed by oxalaldehyde (40% in water, 0.889 mL) and ammonium acetate (473 mg) were added to a stirred solution of N-cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-formylphenethoxy)propanamide [Example 10, Step ii)] (400 mg) in methanol (3 mL). The mixture was stirred for 36 h. DCM was added and the mixture was washed with water. The volatiles were removed under vacuum and the crude product was purified by flash silica chromatography, elution gradient 50%-100% ethyl acetate in isohexane to afford the subtitled compound (98 mg). 1H NMR (400 MHz, CD3OD) δ 7.42-7.31 (m, 4H), 7.22 (d, J=1.5 Hz, 1H), 7.02 (d, J=1.3 Hz, 1H), 4.54 and 4.39 (2×t, J=5.5 Hz, 1H), 4.06-3.98 and 3.70-3.62 (2×m, 1H), 4.06 (q, J=7.3 Hz, 2H), 3.74-3.63 (m, 4H), 3.39-3.25 (m, 2H), 3.36 (s, 3H), 3.34 (s, 3H), 2.93-2.88 (m, 2H), 2.69-2.61 (m, 2H), 1.82-1.02 (m, 10H), 1.34 (t, J=6.8 Hz, 3H); a ˜1:1 mixture of rotamers is observed.

Workup

  1. washthe mixture was washed with water
  2. customThe volatiles were removed under vacuum
  3. customthe crude product was purified by flash silica chromatography, elution gradient 50%-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-a434fec82db7409f9336860b360dfede
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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