Diethyl chlorophosphate → N-(10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)-5-methyl-1,2-oxazole-4-carboxamide

HRID 1059430Notes

Reaction equation

HRID 1059430 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[CH:4][C:3]=1[C:7]([OH:9])=O.P(Cl)(OCC)(OCC)=O.[NH2:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]2[S:29][C:28]3[N:30]=[CH:31][CH:32]=[N:33][C:27]=3[N:26]([CH2:34][O:35][CH3:36])[C:25]=2[CH:37]=1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C>[CH3:36][O:35][CH2:34][N:26]1[C:25]2[CH:37]=[C:21]([CH2:20][NH:19][C:7]([C:3]3[CH:4]=[N:5][O:6][C:2]=3[CH3:1])=[O:9])[CH:22]=[CH:23][C:24]=2[S:29][C:28]2[N:30]=[CH:31][CH:32]=[N:33][C:27]1=2

Participants

8

Reactant 4

HCID 13139Diethyl chlorophosphateHCID 25517Ammonium ChlorideHCID 14252405-Methylisoxazole-4-carboxylic acidHCID 186704238-aminomethyl-10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazine

Product 1

HCID 18670495N-(10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)-5-methyl-1,2-oxazole-4-carboxamideYield 49.6%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 520 mg of 5-methyl-1,2-oxazole-4-carboxylic acid and 0.75 ml of triethylamine in tetrahydrofuran (10 ml) was ice-cooled. After adding 0.8 ml of diethyl chlorophosphate, the resulting mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added 5 ml of a solution of 750 mg of 8-aminomethyl-10-methoxymethyl-10H-pyrazino[2,3-b][1,4]-benzothiazine in tetrahydrofuran and the resulting mixture was stirred at room temperature for 1.5 hours. Next, the reaction mixture was distributed into ethyl acetate and an aqueous solution of ammonium chloride. The organic layer was extracted, washed with water and dried over anhydrous sodium 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 520 mg of N-(10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)-5-methyl-1,2-oxazole-4-carboxamide. Further, the product was treated by the same method as the one of Example 434 to thereby give 310 mg of the title compound as yellow crystals.

Workup

  1. temperaturecooled
  2. stirringthe resulting mixture was stirred at room temperature for 1.5 hours
  3. extractionThe organic layer was extracted
  4. washwashed with water
  5. dry with materialdried over anhydrous sodium 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-b448375fa64c465a8fa6487554a71adb
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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