Triethylamine → (11S)-11-methyl-3-[(E)-2-(methylsulfonyl)ethenyl]-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline

HRID 221625Notes

Reaction equation

HRID 221625 reaction equation
C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.Br[C:31]1[CH:40]=[C:39]2[C:34]([C:35]3[N:43]4[C@@H:44]([CH3:48])[CH2:45][O:46][CH2:47][C:42]4=[N:41][C:36]=3[CH:37]=[N:38]2)=[CH:33][CH:32]=1.[CH:49]([S:51]([CH3:54])(=[O:53])=[O:52])=[CH2:50].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)(Cl)Cl.C(Cl)Cl>[CH3:48][C@@H:44]1[N:43]2[C:35]3[C:34]4[C:39](=[CH:40][C:31](/[CH:50]=[CH:49]/[S:51]([CH3:54])(=[O:53])=[O:52])=[CH:32][CH:33]=4)[N:38]=[CH:37][C:36]=3[N:41]=[C:42]2[CH2:47][O:46][CH2:45]1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 19354Methyl vinyl sulfoneHCID 80271Tri-o-tolylphosphineHCID 67157683(11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline

Product 1

HCID 86624133(11S)-11-methyl-3-[(E)-2-(methylsulfonyl)ethenyl]-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolineYield 46.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A scintillation vial was charged with palladium acetate (35.2 mg, 0.165 mmol), tri-o-tolylphosphine (96 mg, 0.32 mmol), anhydrous DMF (1.0 mL) and triethylamine (1.31 mL, 9.4 mmol). The orange homogeneous solution was then added to a solution of (11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline (1.00 g, 3.14 mmol) dissolved in 20 mL of anhydrous DMF followed by the addition of a solution of methyl vinyl sulfone (400 mg, 3.77 mmol) dissolved in 1.0 mL of anhydrous DMF. The mixture was transferred to a glass vessel and the vessel was purged with N2, sealed and heated to 120° C. for 18 hours. The reaction mixture was cooled and concentrated to dryness under reduced pressure to give a golden solid. The solid was treated with CH2Cl2 and saturated aqueous K2CO3 solution and the layers were separated. The organic layer was concentrated to dryness to give a solid. Chromatography (SiO2, 0-15% CMA/CHCl3) gave a white solid that was crystallized from acetonitrile to give 0.5 g of (11S)-11-methyl-3-[(E)-2-(methylsulfonyl)ethenyl]-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline as white crystals, mp 249-250° C.

Workup

  1. customThe mixture was transferred to a glass vessel
  2. customthe vessel was purged with N2
  3. customsealed
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated to dryness under reduced pressure
  6. customto give a golden solid
  7. customthe layers were separated
  8. concentrationThe organic layer was concentrated to dryness
  9. customto give a solid
  10. customthat was crystallized from acetonitrile

Sources & evidence

ORD record
ord-c61b2dfd0b9f40398b0e1c3ce33f10c4
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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