N-methyl-N-(trimethylsilyl)trifluoroacetamide → 1-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)-1-azoniabicyclo[2.2.2]octane-4-carboxylate

HRID 1059375Notes

Reaction equation

HRID 1059375 reaction equation
[N:1]12[CH2:8][CH2:7][C:4]([C:9]([OH:11])=[O:10])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.CN([Si](C)(C)C)C(=O)C(F)(F)F.Cl[CH2:25][C:26]1[CH:27]=[CH:28][C:29]2[S:34][C:33]3[N:35]=[CH:36][CH:37]=[N:38][C:32]=3[NH:31][C:30]=2[CH:39]=1>C(#N)C>[N:38]1[C:32]2[NH:31][C:30]3[CH:39]=[C:26]([CH2:25][N+:1]45[CH2:8][CH2:7][C:4]([C:9]([O-:11])=[O:10])([CH2:5][CH2:6]4)[CH2:3][CH2:2]5)[CH:27]=[CH:28][C:29]=3[S:34][C:33]=2[N:35]=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 32510N-methyl-N-(trimethylsilyl)trifluoroacetamideHCID 117470388-Chloromethyl-10H-pyrazino[2,3-b][1,4]benzothiazineHCID 13760939Quinuclidine-4-carboxylic acid

Product 1

HCID 186706771-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)-1-azoniabicyclo[2.2.2]octane-4-carboxylateYield 14.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

0.620 g of 1-azabicyclo[2.2.2]octane-4-carboxylic acid was dissolved in 40 ml of acetonitrile. After adding 3.98 g of N-methyl-N-(trimethylsilyl)trifluoroacetamide, the resulting mixture was stirred for 2 hours. Next, 0.998 g of 8-chloromethyl-10H-pyrazino[2,3-b][1,4]benzothiazine was added thereto and the resulting mixture was heated under reflux for 4 hours. After distilling off the solvent under reduced pressure, the residue was dissolved in methanol/dichloromethane. After adding diethyl ether, the mixture was filtered and the residue was purified by High-porous gel chromatography (CHP20P, mfd by Mitsubishi Chemical Industries, 75-150μ) (eluted with methanol/water) to thereby give 0.21 g of the title compound as a yellow powder.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux for 4 hours
  3. distillationAfter distilling off the solvent under reduced pressure
  4. dissolutionthe residue was dissolved in methanol/dichloromethane
  5. additionAfter adding diethyl ether
  6. filtrationthe mixture was filtered
  7. customthe residue was purified by High-porous gel chromatography (CHP20P, mfd by Mitsubishi Chemical Industries, 75-150μ) (eluted with methanol/water)

Sources & evidence

ORD record
ord-749fd764ca0d4a5ab2632083708a8b52
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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