2,6-Dimethyl-4-(trimethyl-stannyl)pyridine → ethyl (S)-10-(2,6-dimethyl-4-pyridinyl)-8,9-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate

HRID 1904598Notes

Reaction equation

HRID 1904598 reaction equation
Br[C:2]1[C:3]([F:23])=[C:4]([F:22])[C:5]2[C:15](=[O:16])[C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][N:7]3[C@@H:8]([CH3:12])[CH2:9][O:10][C:11]=1[C:6]=23.[CH3:24][C:25]1[CH:30]=[C:29]([Sn](C)(C)C)[CH:28]=[C:27]([CH3:35])[N:26]=1>C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:24][C:25]1[CH:30]=[C:29]([C:2]2[C:3]([F:23])=[C:4]([F:22])[C:5]3[C:15](=[O:16])[C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][N:7]4[C@@H:8]([CH3:12])[CH2:9][O:10][C:11]=2[C:6]=34)[CH:28]=[C:27]([CH3:35])[N:26]=1

Participants

5

Reactant 2

HCID 129132682,6-Dimethyl-4-(trimethyl-stannyl)pyridineHCID 14501357ethyl (S)-10-bromo-8,9-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate

Product 1

HCID 14501359ethyl (S)-10-(2,6-dimethyl-4-pyridinyl)-8,9-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylateYield 72.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 19.35 g ethyl (S)-10-bromo-8,9-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate, 16.20 g 2,6-dimethyl-4-(trimethylstannyl)pyridine, 0.88 g dichlorobis(triphenylphosphine)palladium in 200 ml ethanol was placed in a stainless steel Parr apparatus and the system flushed with nitrogen and pressurized to about 80 psi with nitrogen. The system was heated at 150° C. for 4 hours. The reaction mixture was cooled and concentrated in vacuo, and the residue was taken up in chloroform, filtered and chromatographed on silica gel using 5% methanol in chloroform to give 14.90 g ethyl (S)-10-(2,6-dimethyl-4-pyridinyl)-8,9-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate.

Workup

  1. customthe system flushed with nitrogen
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated in vacuo
  4. filtrationfiltered
  5. customchromatographed on silica gel using 5% methanol in chloroform

Sources & evidence

ORD record
ord-5d91376135124ef391f0ad07e8a923fd
Source dataset
uspto-grants-1989_06
Patent number
US04839355

Reaction notes

Loading…