Phosphorus oxychloride → 7-(3-Chloropropoxy)-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinoline-3-carbonitrile

HRID 1593777Notes

Reaction equation

HRID 1593777 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[NH:9][CH:10]=[C:11]([C:25]#[N:26])[C:12]([NH:14][C:15]1[CH:20]=[C:19]([O:21][CH3:22])[C:18]([Cl:23])=[CH:17][C:16]=1[Cl:24])=O.P(Cl)(Cl)(Cl)=O>C(#N)C>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:27]([C:12]([NH:14][C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([Cl:23])=[CH:17][C:16]=3[Cl:24])=[C:11]([C:25]#[N:26])[CH:10]=[N:9]2)=[CH:28][C:29]=1[O:30][CH3:31]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 693108673-(3-chloropropoxy)-4-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide

Product 1

HCID 110489207-(3-Chloropropoxy)-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinoline-3-carbonitrileYield 45.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 3-(3-chloropropoxy)-4-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide (462 mg, 0.95 mmol) in 40 mL of acetonitrile was heated to reflux and phosphorous oxychloride (0.60 mL) was added dropwise, via syringe. The reaction mixture was heated at reflux overnight, then cooled to room temperature and concentrated in vacuo. The residue was cooled to 0° C. and saturated aqueous sodium bicarbonate was added. The mixture was stirred for 10 minutes and the solid was collected by filtration, washed with water. The solid was suspended in hot ethyl acetate and methanol and then filtered to provide 200 mg of 7-(3-chloropropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 2.30 (m, 2H), 3.84 (t, J=6 Hz, 1H), 3.88 (s, 3H), 4.01 (s, 3H), 4.32 (t, J=6 Hz, 2H), 7.46 (s, 1H), 7.51 (s, 1H), 7.81 (s, 1H), 8.14 (s, 1H), 8.81 (s, 1H), 10.83 (br s, 1H), MS (ES) m/z 466.1, 468.1 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux overnight
  5. concentrationconcentrated in vacuo
  6. temperatureThe residue was cooled to 0° C.
  7. additionsaturated aqueous sodium bicarbonate was added
  8. filtrationthe solid was collected by filtration
  9. washwashed with water
  10. filtrationmethanol and then filtered

Sources & evidence

ORD record
ord-a459a6f5b40d4b62a7b34307efae1ca1
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Reaction notes

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