Cesium carbonate → 2-(4-Fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

HRID 1671962노트

반응식

HRID 1671962 반응식
Br[C:2]1[C:3]([CH3:22])=[CH:4][C:5]([O:20][CH3:21])=[C:6]([CH:19]=1)[C:7]([NH:9][C:10]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:12][CH2:11]1)=[O:8].O1CCOCC1.[F:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[O:37][C:38]3[CH:48]=[CH:47][C:46](B4OC(C)(C)C(C)(C)O4)=[CH:45][C:39]=3[C:40]=2[C:41]([NH:43][CH3:44])=[O:42])=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[O:37][C:38]3[CH:48]=[CH:47][C:46]([C:2]4[CH:19]=[C:6]([C:7](=[O:8])[NH:9][C:10]5([C:13]6[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=6)[CH2:12][CH2:11]5)[C:5]([O:20][CH3:21])=[CH:4][C:3]=4[CH3:22])=[CH:45][C:39]=3[C:40]=2[C:41]([NH:43][CH3:44])=[O:42])=[CH:32][CH:31]=1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 592754752-(4-fluorophenyl)-N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 672118695-bromo-2-methoxy-4-methyl-N-(1-(pyridin-2-yl)cyclopropyl)benzamide

생성물 1

HCID 592757562-(4-Fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide수율 57%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6344Dichloromethane용매

반응 조건

온도
85 °C

실험 절차

Alternative synthesis. To a sealed tube was added 5-bromo-2-methoxy-4-methyl-N-(1-(pyridin-2-yl)cyclopropyl) benzamide (1.9024 g, 5.27 mmol), dioxane (70 mL), 2-(4-fluorophenyl)-N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (2.529 g, 6.40 mmol), cesium carbonate (2.57 g, 7.90 mmol), water (14.00 mL) and finally tetrakis(triphenylphosphine)palladium(0) (0.304 g, 0.263 mmol). The vessel was sealed and heated for 16 hours at 85° C. in an oil bath. The mixture was cooled to room temperature, diluted with 20 ml of DCM and pushed through a plug of celite. The resulting dark solution was concentrated to a grey oil. To this residue was added 20 ml of 0.5N HCl, followed by 20 ml of water. The flask was cooled in an ice bath for 30 minutes and the resulting solids were collected by filtration and washed with 10 ml of water and dried under vacuum. The crude product was taken up in 1:1 ethyl acetate/hexane and pushed through a plug of silica gel. Solvent was removed giving 1.65 grams of the product as a light tan solid.

후처리

  1. customAlternative synthesis
  2. customThe vessel was sealed
  3. temperatureThe mixture was cooled to room temperature
  4. concentrationThe resulting dark solution was concentrated to a grey oil
  5. additionTo this residue was added 20 ml of 0.5N HCl
  6. temperatureThe flask was cooled in an ice bath for 30 minutes
  7. filtrationthe resulting solids were collected by filtration
  8. washwashed with 10 ml of water
  9. customdried under vacuum
  10. customSolvent was removed

출처 및 근거

ORD 기록
ord-74f041ab290f4db2a0f868d04a007513
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994171B2

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