Betahistine → HCID 15287679, compound

HRID 1655435Notes

Reaction equation

HRID 1655435 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]([C:11]1[CH:12]=[C:13]([S:21][C@@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[S:28][CH2:29][C:30]([OH:32])=O)[CH:14]=[C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:16]=1)([CH3:10])[CH3:9].[CH3:33][NH:34][CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1.C(N(CC)CC)C>C1C=CC=CC=1>[CH3:20][C:17]([C:15]1[CH:14]=[C:13]([S:21][C@@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[S:28][CH2:29][C:30]([N:34]([CH3:33])[CH2:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)=[O:32])[CH:12]=[C:11]([C:8]([CH3:10])([CH3:9])[CH3:7])[CH:16]=1)([CH3:19])[CH3:18]

Participants

6

Reactant 4

HCID 2366BetahistineHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 54279934HCID 54279934, compound

Product 1

HCID 15287679HCID 15287679, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

Oxalyl chloride (0.19 g, 0.0015 moles) was added by syringe to a cold (10° C.) solution of trans-[[2-[[3,5-bis(1,1-dimethylethyl)phenyl]thio]cyclohexyl]thio]acetic acid (0.55 g, 0.0014 moles) in benzene (50 ml). The cold bath was removed and the reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was concentrated to an oil (rotary evaporator). The oil was dissolved in toluene (50 ml) and concentrated to an oil. The process was repeated using tetrahydrofuran (25 ml) instead of toluene. The residue was dissolved in tetrahydrofuran (50 ml). To this solution was added 2-(2-methylaminoethyl)pyridine (0.19 g, 0.0014 moles) and triethylamine (0.22 g) and the reaction mixture was stirred at room temperature for 48 hours. The white solid precipitate was removed by filtration and washed with ethyl acetate (25 ml). The filtrate was concentrated to give the crude product as an oil. The product was purified by silica gel chromatography and dried in vacuo at 100° C. for 1 hour to give the title compound. The structure assignment was supported by NMR, infrared spectroscopy and elemental analysis.

Workup

  1. customThe cold bath was removed
  2. concentrationThe reaction mixture was concentrated to an oil (rotary evaporator)
  3. dissolutionThe oil was dissolved in toluene (50 ml)
  4. concentrationconcentrated to an oil
  5. dissolutionThe residue was dissolved in tetrahydrofuran (50 ml)
  6. stirringthe reaction mixture was stirred at room temperature for 48 hours
  7. customThe white solid precipitate was removed by filtration
  8. washwashed with ethyl acetate (25 ml)
  9. concentrationThe filtrate was concentrated
  10. customto give the crude product as an oil
  11. customThe product was purified by silica gel chromatography
  12. customdried in vacuo at 100° C. for 1 hour

Sources & evidence

ORD record
ord-9a89c7cfcfca4ed983550e4953c1a7f9
Source dataset
uspto-grants-1993_10
Patent number
US05250567

Reaction notes

Loading…