Ethanol → 2-(4-(5-cyanopyridin-3-yl)phenyl)-N-isobutyl-2-methylpropanamide

HRID 1175587노트

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HRID 1175587 반응식
[CH2:1]([NH:5][C:6](=[O:25])[C:7]([CH3:24])([C:9]1[CH:14]=[CH:13][C:12](B2OC(C)(C)C(C)(C)O2)=[CH:11][CH:10]=1)[CH3:8])[CH:2]([CH3:4])[CH3:3].Br[C:27]1[CH:28]=[N:29][CH:30]=[C:31]([CH:34]=1)[C:32]#[N:33].C(=O)([O-])[O-].[K+].[K+].C(O)C>C1(C)C=CC=CC=1.CCOC(C)=O.O.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>[C:32]([C:31]1[CH:34]=[C:27]([C:12]2[CH:11]=[CH:10][C:9]([C:7]([CH3:8])([CH3:24])[C:6]([NH:5][CH2:1][CH:2]([CH3:3])[CH3:4])=[O:25])=[CH:14][CH:13]=2)[CH:28]=[N:29][CH:30]=1)#[N:33]

참가 물질

9

반응물 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 7367935-BromonicotinonitrileHCID 68776318N-isobutyl-2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanamide

생성물 1

HCID 160051962-(4-(5-cyanopyridin-3-yl)phenyl)-N-isobutyl-2-methylpropanamide수율 88.1%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 1140Toluene용매HCID 22728543Water ethylacetate용매

실험 절차

N-isobutyl-2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanamide (example 23a) (14.86 g, 43.03 mmol), 5-bromonicotinonitrile (7.50 g, 40.98 mmol) and potassium carbonate (11.33 g, 81.96 mmol) were mixed in toluene (75 mL), ethanol (15 mL) and water (11.25 mL). The mixture was degassed for 30 minutes and Pd(PPh3)4 (950 mg, 0.82 mmol) was added. The reaction mixture was heated to reflux for 16 hr and cooled to room temperature then diluted with EtOAc/water, washed successively with water and brine, dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel (eluant 40% EtOAc in hexane) twice, then recrystallized from EtOAC/hexane and co-evaporated with ethanol to give 11.6 g of the product as a white solid in 88% yield. 1H NMR (400 MHz, DMSO-d6): δ 0.75 (d, 6H)), 1.48 (s, 6H), 1.70 (m, 1H), 2.85 (t, 2H), 7.45 (m, 3H), 7.8 (d, 2H), 8.65 (t, 1H), 9 (d, 1H), 9.2 (d, 1H). MS(M+H, 322).

후처리

  1. customThe mixture was degassed for 30 minutes
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 16 hr
  4. washwashed successively with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was chromatographed on silica gel (eluant 40% EtOAc in hexane) twice
  9. customrecrystallized from EtOAC/hexane and co-evaporated with ethanol

출처 및 근거

ORD 기록
ord-73017803f50a4061a95ac01a354d647d
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842324B2

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