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

HRID 646038Notes

Reaction equation

HRID 646038 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-b0111e21f3734ec58f3605ff3a2d539c
Source dataset
uspto-grants-2010_04
Patent number
US07705028B2

Reaction notes

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