Tetrahydrofuran → Ethyl 4-[1-[(10-(methoxymethyl)-10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl]carbamoyl]piperidin-4-yl]-2-methylbutanoate

HRID 1059364Notes

Reaction equation

HRID 1059364 reaction equation
[N:1]1[C:10]2[NH:9][C:8]3[CH:11]=[C:12]([CH2:15]C(O)=O)[CH:13]=[CH:14][C:7]=3[S:6][C:5]=2[N:4]=[CH:3][CH:2]=1.C([N:21]([CH2:24]C)CC)C.[N-]=[N+]=[N-].P([O-])(OC1C=CC=CC=1)(OC1C=CC=CC=1)=[O:30].[NH:46]1[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][CH:54]([CH3:60])[C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH2:48][CH2:47]1.[O:61]1[CH2:65]CC[CH2:62]1>C(OCC)(=O)C>[CH3:62][O:61][CH2:65][N:9]1[C:8]2[CH:11]=[C:12]([CH2:15][NH:21][C:24]([N:46]3[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][CH:54]([CH3:60])[C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH2:48][CH2:47]3)=[O:30])[CH:13]=[CH:14][C:7]=2[S:6][C:5]2[N:4]=[CH:3][CH:2]=[N:1][C:10]1=2

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 11298836Ethyl 4-(piperidin-4-yl)-2-methylbutanoateHCID 1867013310H-Pyrazino[2,3-b][1,4]benzothiazine-8-acetic acidHCID 21964642Diphenylphosphate azide

Product 1

HCID 18670562Ethyl 4-[1-[(10-(methoxymethyl)-10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl]carbamoyl]piperidin-4-yl]-2-methylbutanoate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.7 g of 10H-pyrazino[2,3-b][1,4]benzothiazine-8-acetic acid in tetrahydrofuran (50 ml) were added 0.35 ml of triethylamine and 0.55 ml of diphenyl phosphate azide and the resulting mixture was stirred at room temperature for 3 hours. Next, it was heated under reflux for 1.5 hours. After adding 0.55 g of ethyl 4-(piperidin-4-yl)-2-methylbutanoate, the resulting mixture was reacted at room temperature for 1 hour. After adding ethyl acetate, the reaction mixture 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 dichloromethane/methanol) to thereby give 0.66 g of the title compound as a yellow oily substance.

Workup

  1. temperatureNext, it was heated
  2. temperatureunder reflux for 1.5 hours
  3. customthe resulting mixture was reacted at room temperature for 1 hour
  4. washthe reaction mixture was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationAfter distilling off the solvent under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (eluted with dichloromethane/methanol)

Sources & evidence

ORD record
ord-e7bbc59923dd46089f7334316f7b69c9
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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