Triethylamine → HCID 11236296, compound

HRID 1830601Notes

Reaction equation

HRID 1830601 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][C@H:16]([NH2:24])[CH2:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[CH2:11][CH2:10]1.C(N(CC)CC)C.[CH3:32][C:33]1([C:39](Cl)=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][C@H:16]([NH:24][C:39]([C:33]2([CH3:32])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)=[O:40])[CH2:17][C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)[CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 41892451-Methylcyclohexanecarbonyl chlorideHCID 58651186HCID 58651186, compound

Product 1

HCID 11236296HCID 11236296, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1R)-2-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-1-pyridin-4-ylmethyl-ethylamine (726 mg.; 2.23 mmol, from Example 8) in dichloromethane (30 mL) at 0° C. was added triethylamine (0.62 mL; 4.45 mmol) and 1-methyl-1-cyclohexanecarbonyl chloride (356 mg.; 2.23 mmol). The reaction mixture was stirred while allowing to warm to ambient temperature over 1 hour, washed sequentially with saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered, and the solvent removed in vacuo. The crude residue was purified by flash chromatography on silica gel (2% methanol/chloroform) to yield the free base of the title compound as a clear oil (695 mg.; 69%). Treatment with an equimolar amount of fumaric acid in ethanol afforded the fumarate salt as a white amorphous solid, m.p. 145° C.; MS EI M+ @ m/z 450; 1H NMR, 400 MHz, DMSO-d6. Analysis for C27H38N4O2C4H4O4.0.5H2O Calculated: C, 64.68; H, 7.53; N, 9.73 Found: C, 64.97; H, 7.53; N, 9.66

Workup

  1. washwashed sequentially with saturated aqueous NaHCO3 and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customthe solvent removed in vacuo
  5. customThe crude residue was purified by flash chromatography on silica gel (2% methanol/chloroform)

Sources & evidence

ORD record
ord-f5ce683621a0414987e3a847e3f934bd
Source dataset
uspto-grants-2006_06
Patent number
US07067518B2

Reaction notes

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