Cesium carbonate → 5-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one

HRID 1845902노트

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HRID 1845902 반응식
[Cl:1][C:2]1[N:7]=[C:6]2[S:8][C:9](=[O:11])[NH:10][C:5]2=[CH:4][CH:3]=1.CN1C(=O)CCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:26][CH:27]1[CH2:29][C:28]1([F:31])[F:30]>C(OCC)(=O)C.O1CCOCC1>[Cl:1][C:2]1[N:7]=[C:6]2[S:8][C:9](=[O:11])[N:10]([CH2:26][CH:27]3[CH2:29][C:28]3([F:31])[F:30])[C:5]2=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 27614022-(Bromomethyl)-1,1-difluorocyclopropaneHCID 144231285-Chlorothiazolo[5,4-b]pyridin-2(1H)-one

생성물 1

HCID 866765045-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
95 °C

실험 절차

To a round bottom flask was added 5-chloro[1,3]thiazolo[5,4-b]pyridin-2(1H)-one (1-4) (3.5 g, 19 mmol), anhydrous NMP (30 mL), anhydrous 1,4-dioxane (60 mL), cesium carbonate (12 g, 37 mmol), followed by 2-(bromomethyl)-1,1-difluorocyclopropane (3.4 g, 20 mmol). The reaction mixture was then heated to 95° C. while stirring in a hot oil bath for 18 hours. The crude reaction mixture was then cooled to room temperature, then suspended in ethyl acetate and washed with a saturated solution of sodium bicarbonate, followed by water, then brine, dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel chromatography (0-40% EtOAc/Hex) to give 5-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one (1-5) as a tan solid. HRMS (M+H)+: observed=277.0008, calculated=277.0008.

후처리

  1. customThe crude reaction mixture
  2. temperaturewas then cooled to room temperature
  3. washwashed with a saturated solution of sodium bicarbonate
  4. dry with materialbrine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica gel chromatography (0-40% EtOAc/Hex)

출처 및 근거

ORD 기록
ord-72bc047dd426416f89f9f4caa90f4931
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952005B2

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