Triethylamine → Ethyl 4-[1-[(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)carbonyl]piperidin-4-yl]-2-methylbutanoate

HRID 1059361Notes

Reaction equation

HRID 1059361 reaction equation
[N:1]1[C:10]2[NH:9][C:8]3[CH:11]=[C:12]([C:15]([OH:17])=O)[CH:13]=[CH:14][C:7]=3[S:6][C:5]=2[N:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.P(Cl)(OCC)(OCC)=O.[NH:34]1[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][CH:42]([CH3:48])[C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:36][CH2:35]1>O1CCCC1.C(OCC)(=O)C>[N:1]1[C:10]2[NH:9][C:8]3[CH:11]=[C:12]([C:15]([N:34]4[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][CH:42]([CH3:48])[C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:36][CH2:35]4)=[O:17])[CH:13]=[CH:14][C:7]=3[S:6][C:5]=2[N:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 13139Diethyl chlorophosphateHCID 11298836Ethyl 4-(piperidin-4-yl)-2-methylbutanoateHCID 1867033910H-pyrazino[2,3-b][1,4]benzothiazine-8-carboxylic acid

Product 1

HCID 18670718Ethyl 4-[1-[(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)carbonyl]piperidin-4-yl]-2-methylbutanoateYield 73.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1 g of 10H-pyrazino[2,3-b][1,4]-benzothiazine-8-carboxylic acid in tetrahydrofuran (50 ml) were added under ice-cooling 0.6 ml of triethylamine and 0.55 ml of diethyl chlorophosphate. The resulting mixture was reacted at room temperature for 0.5 hour. Next, 0.66 g of ethyl 4-(piperidin-4-yl)-2-methylbutanoate was added thereto and the resulting mixture was stirred at room temperature for 12 hours. After adding ethyl acetate to the reaction mixture, the organic layer was washed with water and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 1.0 g of the title compound as a yellow oily substance.

Workup

  1. customThe resulting mixture was reacted at room temperature for 0.5 hour
  2. washthe organic layer was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationAfter distilling off the solvent under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3c86eb56ff4144599a5338b550bfe495
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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