Triethylamine → Ethyl(E)-3-[6-[(10-methoxymethyl-10H-pyrazino[2,3-b][1,4]-benzothiazin-8-yl)-(tert-butyldimethylsiloxy)methyl]pyridin-2-yl]-2-propenoate

HRID 1059409Notes

Reaction equation

HRID 1059409 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[C:9]2[CH:10]=[CH:11][C:12]3[S:17][C:16]4[N:18]=[CH:19][CH:20]=[N:21][C:15]=4[N:14]([CH2:22][O:23][CH3:24])[C:13]=3[CH:25]=2)[CH:5]=[CH:4][CH:3]=1.[C:34]([O:38][CH2:39][CH3:40])(=[O:37])[CH:35]=[CH2:36].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[CH3:24][O:23][CH2:22][N:14]1[C:13]2[CH:25]=[C:9]([CH:8]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[C:6]3[N:7]=[C:2](/[CH:36]=[CH:35]/[C:34]([O:38][CH2:39][CH3:40])=[O:37])[CH:3]=[CH:4][CH:5]=3)[CH:10]=[CH:11][C:12]=2[S:17][C:16]2[N:18]=[CH:19][CH:20]=[N:21][C:15]1=2

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 11776TriphenylphosphineHCID 186705248-[(6-Bromopyridin-2-yl)-(tert-butyldimethylsiloxy)methyl]-10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazine

Product 1

HCID 18670598Ethyl(E)-3-[6-[(10-methoxymethyl-10H-pyrazino[2,3-b][1,4]-benzothiazin-8-yl)-(tert-butyldimethylsiloxy)methyl]pyridin-2-yl]-2-propenoate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 0.72 g of 8-[(6-bromopyridin-2-yl)-(tert-butyldimethylsiloxy)methyl]-10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazine in N,N-dimethylformamide (8 ml) were added 0.17 ml of ethyl acrylate, 0.22 ml of triethylamine, 12 mg of palladium (II) acetate and 33 mg of triphenylphosphine and the resulting mixture was heated to 90° C. for 30 hours. Then the reaction mixture was brought back to room temperature and distributed into water and ethyl acetate. The organic layer was extracted, washed successively with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and filtered. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (diluted with dichloromethane/ethyl acetate) to thereby give 540 mg of the title compound as a yellow oily substance.

Workup

  1. customwas brought back to room temperature
  2. extractionThe organic layer was extracted
  3. washwashed successively with water
  4. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. distillationAfter distilling off the solvent under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (diluted with dichloromethane/ethyl acetate)

Sources & evidence

ORD record
ord-1923915fbb0d43578a85e02b2137e2be
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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