Methanesulfonyl chloride → HCID 69819408, compound

HRID 1006369Notes

Reaction equation

HRID 1006369 reaction equation
[CH3:1][S:2]([Cl:5])(=[O:4])=[O:3].[ClH:6].Cl.Cl.[CH:9]([C@H:22]1[N:27]2[CH2:28][CH2:29][NH:30][CH2:31][C@H:26]2[CH2:25][N:24]([CH2:32][C:33]2[CH:38]=[C:37]([N:39]3[C:43]([C:44]([F:47])([F:46])[F:45])=[N:42][N:41]=[N:40]3)[CH:36]=[CH:35][C:34]=2[O:48][CH3:49])[CH2:23]1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(CC)C(C)C)(C)C>ClCCl>[ClH:5].[ClH:6].[CH:9]([C@H:22]1[N:27]2[CH2:28][CH2:29][N:30]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:31][C@H:26]2[CH2:25][N:24]([CH2:32][C:33]2[CH:38]=[C:37]([N:39]3[C:43]([C:44]([F:47])([F:46])[F:45])=[N:42][N:41]=[N:40]3)[CH:36]=[CH:35][C:34]=2[O:48][CH3:49])[CH2:23]1)([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86589651HCID 86589651, compound

Product 1

HCID 69819408HCID 69819408, compoundYield 49.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (22.1 mg) was added to a mixture of (4R,9aS)-4-benzhydryl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine trihydrochloride (100 mg) and N,N-diisopropylethylamine (116 μl) in dichloromethane under ice-cooling. After being stirred at the same temperature for 2 hours the mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulphate, and evaporated under reduced pressure. The resulting oil was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol. The fractions containing the objective compound was collected and evaporated under reduced pressure and the resulting residue was treated with 4N hydrogen chloride in ethyl acetate to give (4R,9aR)-4-benzhydryl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]-8-(methylsulfonyl)octahydro-2H-pyrazino[1,2-a]pyrazine dihydrochloride (52.8 mg) as colourless powder.

Workup

  1. temperaturecooling
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with brine
  4. dry with materialdried over magnesium sulphate
  5. customevaporated under reduced pressure
  6. customThe resulting oil was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol
  7. additionThe fractions containing the objective compound
  8. customwas collected
  9. customevaporated under reduced pressure
  10. additionthe resulting residue was treated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-c576dc40075e457aa2968455176913b8
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

Loading…