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

HRID 1593782Notes

Reaction equation

HRID 1593782 reaction equation
[C:1]([C:3](=[CH:17][NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH3:27])=[C:21]([I:28])[CH:20]=1)[C:4]([NH:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=1[Cl:16])=O)#[N:2].P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[Cl:16][C:8]1[CH:9]=[C:10]([Cl:15])[C:11]([O:13][CH3:14])=[CH:12][C:7]=1[NH:6][C:4]1[C:24]2[C:19](=[CH:20][C:21]([I:28])=[C:22]([O:25][CH2:26][CH3:27])[CH:23]=2)[N:18]=[CH:17][C:3]=1[C:1]#[N:2]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychloride2×HCID 692583872-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-[(4-ethoxy-3-iodophenyl)amino]prop-2-enamide

Product 1

HCID 117062174-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-iodo-3-quinolinecarbonitrileYield 76%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-[(4-ethoxy-3-iodophenyl)amino]prop-2-enamide (2.0 g, 3.76 mmol) in 100 mL of toluene was heated to reflux and phosphorous oxychloride (3.5 mL, 37.6 mmol) was added dropwise via syringe. This suspension was heated at reflux for 6 hours and additional phosphorous oxychloride (3.5 mL, 37.6 mmol) was added to slowly give a dark solution. After 72 hours the mixture was cooled to room temperature, the solid was filtered and washed with toluene and ether. The light brown solid was dried under reduced pressure at ˜40° C., overnight, to provide 1.47 g (76%) of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-iodo-3-quinolinecarbonitrile as a yellow solid, mp 213-215° C.; 1H NMR (300 MHz, DMSO-d6) δ 1.48 (t, 3H, J=6.9 Hz), 4.32 (q, 2H, J=6.9 Hz), 3.88 (s, 3H), 7.53 (s, 1H), 7.87 (s, 1H), 8.06 (s, 1H), 8.49 (s, 1H), 9.02 (s, 1H), 11.14 (bs, 1H); MS (ES) m/z514.1 (M+H)+

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperatureThis suspension was heated
  4. temperatureat reflux for 6 hours
  5. customto slowly give a dark solution
  6. filtrationthe solid was filtered
  7. washwashed with toluene and ether
  8. customThe light brown solid was dried under reduced pressure at ˜40° C., overnight

Sources & evidence

ORD record
ord-582d1b16b57f4423b52bf7789d6a470e
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Reaction notes

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