Cesium carbonate → 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone

HRID 1626139노트

반응식

HRID 1626139 반응식
[NH2:1][C:2]1[O:3][CH2:4][C:5]([F:21])([F:20])[C@:6]([C:9]2[C:14]([F:15])=[CH:13][C:12]([OH:16])=[C:11]([N+:17]([O-:19])=[O:18])[CH:10]=2)([CH3:8])[N:7]=1.Br[CH2:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][N:27]=1)=[O:25].C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])O.[Na+]>CC(C)=O.[I-].[K+]>[NH2:1][C:2]1[O:3][CH2:4][C:5]([F:20])([F:21])[C@:6]([C:9]2[C:14]([F:15])=[CH:13][C:12]([O:16][CH2:23][C:24]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][N:27]=3)=[O:25])=[C:11]([N+:17]([O-:19])=[O:18])[CH:10]=2)([CH3:8])[N:7]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 111839252-Bromo-1-(5-chloropyridin-2-yl)ethanoneHCID 710088104-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenol

생성물 1

HCID 710089012-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone수율 92%

시약·촉매·용매 2

HCID 4875Potassium Iodide촉매HCID 180Acetone용매

실험 절차

A dispersion of 4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenol (intermediate F2.1) (120 mg, 393 μmol), 2-bromo-1-(5-chloropyridin-2-yl)ethanone (101 mg, 432 μmol), cesium carbonate (512 mg, 1.57 mmol), and potassium iodide (2 mg, 14.5 μmol) in acetone (5.51 ml) was stirred at room temperature for 20 hours. For the workup, the reaction mixture was poured into a saturated solution of sodium hydrogencarbonate (5 ml) and extracted with dichloromethane (2×5 ml). The combined organic layers were dried over sodium sulphate and evaporated at reduced pressure. The crude 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone (165 mg, 92% yield) was obtained as a red gum. MS (ISP): m/z=459.1 [M+H]+.

후처리

  1. extractionextracted with dichloromethane (2×5 ml)
  2. dry with materialThe combined organic layers were dried over sodium sulphate
  3. customevaporated at reduced pressure

출처 및 근거

ORD 기록
ord-b5b6ab3450b748358dd362ef8f4188eb
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785436B2

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