Toluene → N-(5-(3,4-dimethylphenyl)-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)nicotinamide

HRID 1958139

반응식

HRID 1958139 반응식
Br[C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:22])[C:16]2[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=2)[CH:5]=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].C1(C)C=CC=CC=1.[CH3:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][C:36]=1[CH3:37].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:30][C:31]1[CH:32]=[C:33]([C:2]2[CH:3]=[C:4]([NH:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=3)[CH:5]=[N:6][C:7]=2[O:8][CH2:9][C:10]([F:13])([F:12])[F:11])[CH:34]=[CH:35][C:36]=1[CH3:37]

참가 물질

7

반응물 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343483,4-Dimethylphenylboronic acidHCID 67280716N-(5-bromo-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)nicotinamide

생성물 1

HCID 56961330N-(5-(3,4-dimethylphenyl)-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)nicotinamide수율 65%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8857Ethyl Acetate용매

실험 절차

In a 25 mL sealed tube N-(5-bromo-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)nicotinamide (200 mg, 532 μmol) was combined with toluene (11 mL). Under argon atmosphere, were added 3.4-dimethylbenzeneboronic acid (160 mg, 1.06 mmol), an aqueous solution of sodium carbonate (2M, 0.53 mL) and Pd(dppf)2Cl2 (12 mg, 0.016 mmol). After two hours at 90° C., the dark red suspension was cooled to room temperature, diluted with ethyl acetate (10 mL), and washed with water (10 mL) and brine (10 mL). The aqueous layer was back-extracted with ethyl acetate (15 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. Crystallization from ethyl acetate/heptane (5 mL, 1/2) gave a white solid (96 mg), the filtrate was evaporated to dryness and purified by column chromatography (silica gel, 20 g, 10% to 100% ethyl acetate in heptane) to get a second part of the desired product as a white solid (139 mg). Overall yield was 65%; MS (EI): 402.3 (M+H).

후처리

  1. washwashed with water (10 mL) and brine (10 mL)
  2. extractionThe aqueous layer was back-extracted with ethyl acetate (15 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customCrystallization from ethyl acetate/heptane (5 mL, 1/2)

출처 및 근거

ORD 기록
ord-d17cc4a89f37497c8578cab39ca89fc7
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410107B2

연결된 노트

불러오는 중…