Triethylamine → HCID 15512824, compound

HRID 1978840Notes

Reaction equation

HRID 1978840 reaction equation
[CH2:1]([C@@H:8]([NH:25][CH3:26])[CH2:9][N:10]1[CH2:15][CH2:14][C:13]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[O:23][CH3:24])=[CH:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:34]1([N:40]=[C:41]=[O:42])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>ClCCl>[CH2:1]([C@@H:8]([N:25]([CH3:26])[C:41]([NH:40][CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1)=[O:42])[CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[O:23][CH3:24])[CH2:12][CH2:11]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 18502Cyclohexyl isocyanateHCID 15512827{(1R)-1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-1,2,5,6-tetrahydropyridin-1-yl]-ethyl}-methyl-amine2×

Product 1

HCID 15512824HCID 15512824, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under a N2 atmosphere, a solution of {(1R)-1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-1,2,3,6-tetrahydropyridin-1-yl]-ethyl}-methyl-amine (0.17 g, 0.48 mmole, described as intermediate 12 above) and triethylamine (0.15 mL, 1.0 mmole) in dichloromethane (10 mL) was cooled to 0° C. and a solution of cyclohexyl isocyanate (0.070 mL, 0.51 mmole) was added dropwise. The resulting mixture was stirred at 0° C. to room temperature (ice melt) overnight. The solvent was evaporated and the residue dissolved in EtOAc (25 mL) and water (25 mL). The layers were separated and the organics washed with water (25 mL), brine (30 mL) and dried over Na2SO4. Filtration and concentration gave the crude product which was purified by flash chromatography (elution with EtOAc) to yield 0.19 g (83% yield) of 1-{(1R)-1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-1,2,5,6-tetrahydro-4H-pyridin-1-yl]-ethyl}-3-cyclohexyl-1-methyl-urea. An ethanolic solution of the product was heated to gentle reflux and 1 equivalent of fumaric acid in hot ethyl alcohol solution was added to afford the fumarate salt of the titled compound as a white solid.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in EtOAc (25 mL)
  3. customThe layers were separated
  4. washthe organics washed with water (25 mL), brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationFiltration and concentration
  7. customgave the crude product which
  8. customwas purified by flash chromatography (elution with EtOAc)

Sources & evidence

ORD record
ord-809d0f1df0464e5487b8ea40f698212e
Source dataset
uspto-grants-2001_05
Patent number
US06239126B1

Reaction notes

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