Diisopropylamine → (10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)(pyridin-2-ylmethyl)ketone

HRID 1059410Notes

Reaction equation

HRID 1059410 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.C[O:21][C:22]([C:24]1[CH:25]=[CH:26][C:27]2[S:32][C:31]3[N:33]=[CH:34][CH:35]=[N:36][C:30]=3[N:29]([CH2:37][O:38][CH3:39])[C:28]=2[CH:40]=1)=O.[Cl-].[NH4+]>O1CCCC1.CCCCCC.C(OCC)(=O)C>[CH3:39][O:38][CH2:37][N:29]1[C:28]2[CH:40]=[C:24]([C:22]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[O:21])[CH:25]=[CH:26][C:27]=2[S:32][C:31]2[N:33]=[CH:34][CH:35]=[N:36][C:30]1=2

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 79752-MethylpyridineHCID 25517Ammonium ChlorideHCID 11472176HCID 11472176, compoundHCID 178418339Butyllithium

Product 1

HCID 18670436(10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)(pyridin-2-ylmethyl)ketone

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

0.15 ml of diisopropylamine in tetrahydrofuran (10 ml) was ice-cooled and 1.0 ml of a 1.6 M solution of n-butyllithium in hexane was added thereto. After stirring for 10 minutes, the reaction mixture was cooled to −78° C. After adding 0.15 ml of 2-methylpyridine, the mixture was stirred for 30 minutes and then a solution of 303 mg of methyl(10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)carboxylate in tetrahydrofuran (5 ml) was dropped thereinto. The reaction mixture was brought back to room temperature and distributed into an aqueous solution of ammonium chloride and ethyl acetate. The organic layer was extracted, dried over anhydrous sodium sulfate and filtered. 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 30 mg of (10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)(pyridin-2-ylmethyl)ketone as yellow crystals. This ketone was further treated by the same method as the one of Example 119 to thereby give 13 mg of the title compound as yellow crystals.

Workup

  1. temperaturecooled
  2. stirringthe mixture was stirred for 30 minutes
  3. customwas brought back to room temperature
  4. extractionThe organic layer was extracted
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. distillationAfter distilling off the solvent under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a97d2779e6714e74982b6fcbf40ae257
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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