Phosphorus oxychloride → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile

HRID 1593784

Reaction equation

HRID 1593784 reaction equation
[C:1]([C:3](=[CH:17][NH:18][C:19]1[CH:23]=[CH:22][S:21][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>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:3]([C:1]#[N:2])=[CH:17][N:18]=[C:19]2[CH:23]=[CH:22][S:21][C:20]=12

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 693136752-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-(thien-3-ylamino)prop-2-enamide

Product 1

HCID 53304087-[(2,4-Dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrileYield 71.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-(thien-3-ylamino)prop-2-enamide (500 mg, 1.35 mmol) in 35 mL of acetonitrile was heated to reflux and phosphorous oxychloride (0.84 mL, 8.98 mmol) was added dropwise. The mixture was heated at reflux overnight. The resultant solution was concentrated in vacuo and the residue was cooled to 0° C. Ice water was added followed by the slow addition of saturated aqueous sodium bicarbonate. The mixture was stirred for 10 minutes then partitioned between ethyl acetate and additional saturated aqueous sodium bicarbonate. The organic layer was washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated with ethyl acetate and hexane to provide 337 mg (71%) of 7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile, mp 208-210° C.; 1H NMR (400 MHz, DMSO-d6) δ 3.85 (s, 3H), 7.39 (s, 1H), 7.46 (d, J=5 Hz, 1H), 7.76 (s, 1H), 8.11 (d, J=5 Hz, 1H), 8.61 (s, 1H), 9.74 (s, 1H); MS (ES) m/z348.1, 350.0 (M−H)−

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperatureThe mixture was heated
  4. temperatureat reflux overnight
  5. concentrationThe resultant solution was concentrated in vacuo
  6. additionIce water was added
  7. additionfollowed by the slow addition of saturated aqueous sodium bicarbonate
  8. customthen partitioned between ethyl acetate and additional saturated aqueous sodium bicarbonate
  9. washThe organic layer was washed with water
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was triturated with ethyl acetate and hexane

Sources & evidence

ORD record
ord-6a129cc284ef404cad94f503bd6acf1c
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Linked notes

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