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

HRID 1593784

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HRID 1593784 반응식
[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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
0 °C

실험 절차

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)−

후처리

  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

출처 및 근거

ORD 기록
ord-6a129cc284ef404cad94f503bd6acf1c
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07297795B2

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