Phosphorus oxychloride → 7-Bromo-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-ethoxy-3-quinolinecarbonitrile

HRID 1593779Notes

Reaction equation

HRID 1593779 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[O:26][CH2:27][CH3:28])[NH:5][CH:6]=[C:7]([C:21]#[N:22])[C:8]([NH:10][C:11]1[CH:16]=[C:15]([O:17][CH3:18])[C:14]([Cl:19])=[CH:13][C:12]=1[Cl:20])=O.P(Cl)(Cl)(Cl)=O>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:23]([C:8]([NH:10][C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([Cl:19])=[CH:13][C:12]=3[Cl:20])=[C:7]([C:21]#[N:22])[CH:6]=[N:5]2)=[CH:24][C:25]=1[O:26][CH2:27][CH3:28]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 693154653-bromo-4-ethoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide

Product 1

HCID 116341297-Bromo-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-ethoxy-3-quinolinecarbonitrileYield 37.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 3-bromo-4-ethoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide (630 mg, 1.29 mmol) in 35 mL of acetonitrile was heated to reflux and phosphorous oxychloride (0.80 mL) was added dropwise, via syringe. The reaction mixture was heated at reflux overnight, then cooled to room temperature. The solids were collected by filtration, washed with saturated aqueous sodium bicarbonate. The solids were stirred with saturated aqueous sodium bicarbonate for 1 hour and then collected by filtration, washed with saturated aqueous sodium bicarbonate and water. The solid was recrystallized from methanol and dried in vacuo to provide 225 mg of 7-bromo-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-ethoxy-3-quinolinecarbonitrile as a yellow solid, mp >250° C. 1H NMR (400 MHz, DMSO-d6) δ 1.47 (t, J=7 Hz, 3H), 3.87 (s, 3H), 4.32 (q, J=7 Hz, 2H), 7.45 (s, 1H), 7.82 (s, 1H), 8.16(s, 1H), 8.27 (s, 1H), 8.76 (s, 1H), 10.73 (s, 1H); MS (ES) m/z 466.1, 468.0, 470.1 (M+H)+

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux overnight
  5. filtrationThe solids were collected by filtration
  6. washwashed with saturated aqueous sodium bicarbonate
  7. filtrationcollected by filtration
  8. washwashed with saturated aqueous sodium bicarbonate and water
  9. customThe solid was recrystallized from methanol
  10. customdried in vacuo

Sources & evidence

ORD record
ord-bc85b24153c1483ea94405b65c7e667b
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Reaction notes

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