Cesium carbonate → HCID 11739863, 화합물

HRID 1831944노트

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HRID 1831944 반응식
Br[C:2]1[C:3](=[O:26])[N:4]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[C:27]([O-])([O-])=O.[K+].[K+].C([O-])([O-])=O.[Cs+].[Cs+].CB1OB(C)OB(C)O1>O1CCOCC1.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>[F:17][C:11]1[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[CH2:9][O:8][C:7]1[CH:6]=[CH:5][N:4]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[C:3](=[O:26])[C:2]=1[CH3:27]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 102165503-bromo-4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)pyridin-2(1H)-one

생성물 1

HCID 11739863HCID 11739863, 화합물수율 79%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

To a solution of 3-bromo-4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)-1H-pyridin-2-one (EXAMPLE 107) (0.14 g, 0.32 mmol), K2CO3 (88 mg, 0.64 mmol) and Cs2CO3 (0.10 g, 0.32 mmol) in dioxane (2 mL) was added Pd(PPh3)4 (18 mg, 0.12 mmol), followed by trimethylboroxine (40 mg, 0.32 mmol). The reaction mixture was degassed, purged with argon, and heated at reflux for 4 h. The reaction mixture was cooled to room temperature, and partitioned between water and EtOAc. The organic solution was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 97:3 methylene chloride/MeOH) afforded 4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)-3-methyl-1H-pyridin-2-one as a white solid (0.09 g, 79%): mp 127-129° C.; 1H NMR (300 MHz, CDCl3) δ 7.50-7.40 (m, 1H), 7.35-7.25 (m, 1H), 7.17 (d, J=9 Hz, 1H), 7.06 (d, J=6 Hz, 1H), 7.00-6.80 (m, 4H), 6.12 (d, J=9 Hz, 1H), 5.12 (s, 4H), 2.07 (s, 3H). ES HRMS m/z 360.1180 (M+H C20H16F3NO2 requires 360.1206).

후처리

  1. customThe reaction mixture was degassed
  2. custompurged with argon
  3. temperatureheated
  4. temperatureat reflux for 4 h
  5. custompartitioned between water and EtOAc
  6. washThe organic solution was washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography (silica, eluent methylene chloride to 97:3 methylene chloride/MeOH)

출처 및 근거

ORD 기록
ord-b589f70fa0be4c56827b83f4fff62f48
출처 데이터셋
uspto-grants-2006_06
특허 번호
US07067540B2

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