Hexamethylphosphoramide → 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 1904596노트

반응식

HRID 1904596 반응식
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.CN(C)P(N(C)C)(N(C)C)=O>O1CCOCC1.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

참가 물질

6

반응물 3

HCID 12679HexamethylphosphoramideHCID 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

생성물 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-carboxylate수율 16.6%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

To a mixture of 14.08 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, 10.91 g 2,6-dimethyl-4-trimethylstannylpyridine and 6.3 ml hexamethylphosphoramide in 200 ml dioxane under nitrogen was added 1.27 g dichlorobis(triphenylphosphine)palladium. The reaction mixture was heated at reflux for 24 hrs. Most of the solvent was then removed in vacuo and the residue was extracted with ethyl acetate and water, and then with chloroform. The organic extracts were combined and concentrated. The residue was chromatographed on silica gel using as eluant chloroform and chloroform containing increasing amounts of methanol (1-3%). There was thereby obtained 2.5 g pure 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, light yellow solid, m.p. 295°-297° C., [α]D25 =-34.4° (1% in chloroform).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 24 hrs
  3. customMost of the solvent was then removed in vacuo
  4. extractionthe residue was extracted with ethyl acetate and water
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel using as eluant chloroform and chloroform containing
  7. temperatureincreasing amounts of methanol (1-3%)

출처 및 근거

ORD 기록
ord-24acc5de9c2447b7baebe7bbafb78bbf
출처 데이터셋
uspto-grants-1989_06
특허 번호
US04839355

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