Methanol → HCID 11677731, compound

HRID 1593781Notes

Reaction equation

HRID 1593781 reaction equation
[C:1]([C:3](=[CH:17][NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([I:27])[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].CO.P(Cl)(Cl)(Cl)=O>C(#N)C>[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:27])=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][C:3]=1[C:1]#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 24813Phosphorus oxychlorideHCID 692582152-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-[(3-iodo-4-methoxyphenyl)amino]prop-2-enamide

Product 1

HCID 11677731HCID 11677731, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-[(3-iodo-4-methoxyphenyl)amino]prop-2-enamide (720 mg, 1.39 mmol) in 40 mL of acetonitrile was added 0.2 mL of methanol. The mixture was heated to reflux and phosphorous oxychloride (1.24 mL, 13.9 mmol) was added dropwise, via syringe. This solution was heated at reflux overnight. After 24 hours, the mixture was cooled in an ice-bath and the solid was collected by filtration, washed with cold acetonitrile (40 mL) and then suspended in tetrahydrofuran (100 mL). To both the acetonitrile filtrate and the tetrahydrofuran suspension were added concentrated ammonium hydroxide (2×50 mL) and the mixtures were stirred for 1 hour. Water (2×800 ml) was added and stirring was continued for 2 hours. The resulting solids were combined, washed with hot water and dried under reduced pressure at ˜40° C., overnight, to provide 200 mg (29%) of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-iodo-6-methoxy-3-quinolinecarbonitrile, as yellow solid, mp 253-254° C.; 1H NMR (400 MHz, DMSO-d6) δ 3.86 (s, 3H), 4.00 (s, 3H), 7.33(s, 1H), 7.74(s, 1H), 7.86 (s, 1H), 8.39 (s, 1H), 8.43 (s, 1H), 9.61 (s, 1H); MS (ES) m/z 500.0, 502.1 (M+H)+

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. temperatureThis solution was heated
  4. temperatureat reflux overnight
  5. temperaturethe mixture was cooled in an ice-bath
  6. filtrationthe solid was collected by filtration
  7. washwashed with cold acetonitrile (40 mL)
  8. additionTo both the acetonitrile filtrate and the tetrahydrofuran suspension were added concentrated ammonium hydroxide (2×50 mL)
  9. additionWater (2×800 ml) was added
  10. stirringstirring
  11. waitwas continued for 2 hours
  12. washwashed with hot water
  13. customdried under reduced pressure at ˜40° C., overnight

Sources & evidence

ORD record
ord-d055e43185d24014b585714055d10358
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Reaction notes

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