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

HRID 1693682Notes

Reaction equation

HRID 1693682 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]([NH2:34])=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(N(CC)CC)C.P(Cl)(Cl)(Cl)=O.C(=O)([O-])O.[NH4+]>C(Cl)Cl>[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:17]=[CH:18][C:19]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[C:28]([C:32]#[N:34])=[CH:27][CH:26]=[CH:25]4)=[CH:20][CH:21]=2)=[C:12]([CH:35]([CH3:37])[CH3:36])[O:11][N:10]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 14013Ammonium BicarbonateHCID 24813Phosphorus oxychloride2×HCID 247393296-[4-({[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxamide

Product 1

HCID 247393306-[4-({[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarbonitrileYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxamide (94 mg, 0.18 mmol) and triethylamine (0.111 mL, 0.80 mmol) in methylene chloride (2 mL) at ambient temperature under nitrogen was added phosphorous oxychloride (0.068 mL, 0.71 mmol). The mixture was stirred at ambient temperature for four hours, at which time an additional equivalent of phosphorous oxychloride (0.027 mL) was added. 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 to give the title compound (89 mg, 98%). 1H NMR (CDCl3): 8.24 (d, J=9 Hz, 1H), 8.13 (d, J=9 Hz, 1H), 8.02 (d, J=9 Hz, 1H), 7.82-7.90 (m, 2H), 7.61-7.50 (m, 3H), 7.31-7.52 (m, 3H), 6.88 (d, J=9 Hz, 2H), 4.78 (s, 2H), 3.28-3.42 (m, 1H), 1.34-1.53 (m, 6H). ESI-LCMS m/z 513 (M+H)+.

Workup

  1. additionwas added
  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

Sources & evidence

ORD record
ord-11cfa2cda05144b2aff2b163d8ffd83f
Source dataset
uspto-grants-2012_04
Patent number
US08158665B2

Reaction notes

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