Methanol → Alosetron

HRID 2379162Notes

Reaction equation

HRID 2379162 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][CH2:12][NH:13][CH2:14][C:15]1[N:16]=[CH:17][N:18](S(N(C)C)(=O)=O)[C:19]=1[CH3:20].[C:27](Cl)(Cl)=[O:28].[Cl-].[Cl-].[Cl-].[Al+3].CO>ClCCl>[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]2[C:27](=[O:28])[N:13]([CH2:14][C:15]3[N:16]=[CH:17][NH:18][C:19]=3[CH3:20])[CH2:12][CH2:11][C:3]1=2

Participants

6

Reactant 4

HCID 887MethanolHCID 6371PhosgeneHCID 6451240Aluminum(III) ChlorideHCID 53803528HCID 53803528, compound

Product 1

HCID 2099Alosetron

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-[[[(1-methyl-1H-indol-2-yl)ethyl]amino]methyl]-N,N,5-trimethyl-1H-imidazole-1-sulphonamide (140 mg) in dry dichloromethane (15 ml) was cooled to 5° and the mixture was stirred under nitrogen while phosgene (12% w/w solution in toluene; 1 ml) was added dropwise. The reaction mixture was stirred at room temperature for 2 h, aluminium trichloride (60 mg) was powdered and added, and stirring was continued overnight. After this time methanol (1 ml) was added and the reaction mixture was adsorbed onto FCC silica and purified by FCC eluting with System A (150:8:1) to give the protected derivative of the title compound (42 mg), as a solid, identical (by t.l.c. and m.p.) to the product of Intermediate 27. Deprotection as described in either of Examples 25 or 26 gives the title compound.

Workup

  1. additionwas added dropwise
  2. additionadded
  3. stirringstirring
  4. waitwas continued overnight
  5. custompurified by FCC
  6. washeluting with System A (150:8:1)

Sources & evidence

ORD record
ord-bda355e223a74c89857e7150335a6d66
Source dataset
uspto-grants-1994_11
Patent number
US05360800

Reaction notes

Loading…