Pyridine → 6-[4-({[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxamide

HRID 646038노트

반응식

HRID 646038 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:13]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[C:28]([C:32]([OH:34])=O)=[CH:27][CH:26]=[CH:25]4)=[CH:18][CH:17]=2)=[C:12]([CH:35]([CH3:37])[CH3:36])[O:11][N:10]=1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.[N:53]1C=CC=CC=1.C(=O)([O-])O.[NH4+]>C(#N)C>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[C:13]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[C:28]([C:32]([NH2:53])=[O:34])=[CH:27][CH:26]=[CH:25]4)=[CH:18][CH:17]=2)=[C:12]([CH:35]([CH3:36])[CH3:37])[O:11][N:10]=1

참가 물질

6

반응물 4

HCID 1049PyridineHCID 14013Ammonium BicarbonateHCID 90495Di-tert-butyl dicarbonateHCID 16214849Gsk-8062

생성물 1

HCID 247393296-[4-({[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxamide수율 98.3%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylic acid (97 mg, 0.180 mmol), di-tert-butyl dicarbonate (60 mg, 0.273 mmol), and pyridine (0.021 mL, 0.273 mmol) were combined into anhydrous acetonitrile (5 mL). The mixture was stirred at ambient temperature for half an hour. Ammonium hydrogen carbonate (25 mg, 0.273 mmol) was then added to the mixture and the reaction was stirred at ambient temperature for 48 hours. The solvent was then removed on a rotary evaporator and the crude residue was dissolved in ethyl acetate. The organic solution was then washed with water three times, followed by saturated sodium bicarbonate, and then brine. The crude organic extract was then dried over magnesium sulfate, filtered, and then evaporated to dryness. The residue was washed with hexanes several times to remove the residual di-tert-butyl dicarbonate, and the solids were removed via filtration to give the title compound as a white solid (94 mg, 98%) 1H NMR (CDCl3): δ 8.48 (d, J=9 Hz, 1H), 7.88-8.00 (m, 2H), 7.75 (d, J=9 Hz, 1H), 7.68 (d, J=9 Hz, 1H), 7.58 (d, J=9 Hz, 2H), 7.36-7.51 (m, 3H) 7.25 (d, J=9 Hz, 1 H), 6.88 (d, J=9 Hz, 2H), 6.42 (broad s, 1H), 6.13 (broad s, 1H), 4.81 (s, 2H), 3.26-3.44 (m, 1H), 1.37-1.47 (m, 6H). ESI-LCMS m/z 531 (M+H)+.

후처리

  1. stirringthe reaction was stirred at ambient temperature for 48 hours
  2. customThe solvent was then removed on a rotary evaporator
  3. dissolutionthe crude residue was dissolved in ethyl acetate
  4. washThe organic solution was then washed with water three times
  5. extractionThe crude organic extract
  6. dry with materialwas then dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. washThe residue was washed with hexanes several times
  10. customto remove the residual di-tert-butyl dicarbonate
  11. customthe solids were removed via filtration

출처 및 근거

ORD 기록
ord-b0111e21f3734ec58f3605ff3a2d539c
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07705028B2

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