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7-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[5-(1,3-dioxolan-2-yl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile

HRID 1178664
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HRID 1178664 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[CH:20]=[C:21](I)[S:22][C:13]=12.C([Sn](CCCC)(CCCC)[C:29]1[CH:33]=[C:32]([CH:34]2[O:38][CH2:37][CH2:36][O:35]2)[S:31][CH:30]=1)CCC>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[CH:20]=[C:21]([C:29]3[CH:33]=[C:32]([CH:34]4[O:38][CH2:37][CH2:36][O:35]4)[S:31][CH:30]=3)[S:22][C:13]=12
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 2

HCID 103902087-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrileHCID 22256614Tributyl-(5-[1,3]dioxolan-2-yl-thiophen-3-yl)-stannane

생성물 1

HCID 222566327-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[5-(1,3-dioxolan-2-yl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile수율 75.1%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매3회
HCID 312751,4-Dioxane용매2회

실험 절차

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[3,2-b]pyridine-6-carbonitrile (564 mg, 1.18 mmol), tributyl-(5-[1,3]dioxolan-2-yl-thiophen-3-yl)-stannane (680 mg, 1.52 mmol) and a pinch of bis(triphenylphosphine)palladium(II) chloride in 15 mL of dioxane is heated at reflux for 5 hours. Additional bis(triphenylphosphine)palladium(II) chloride is added and the reaction is heated at reflux overnight. Additional bis(triphenylphosphine)palladium(II) chloride and 10 mL of dioxane are added and the reaction is heated at reflux for 5 hours. The reaction mixture is concentrated in vacuo and partitioned between water and chloroform. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 1:1 hexane:ethyl acetate. The fractions containing product are combined and concentrated in vacuo to provide 447 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[5-(1,3-dioxolan-2-yl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile as white crystals, mp 219–221° C.; 1H NMR (DMSO-d6) δ 3.85 (s, 3H), 3.92–4.10 (m, 4H), 6.08 (s, 1H), 7.36 (s, 1H), 7.63 (s, 1H), 7.75 (s, 1H), 7.80 (s, 1H), 7.97 (s, 1H), 8.60 (s, 1H), 9.69 (s, 1H); MS 502.1 (M−H)−.

후처리

  1. temperatureat reflux for 5 hours
  2. temperaturethe reaction is heated
  3. temperatureat reflux overnight
  4. temperaturethe reaction is heated
  5. temperatureat reflux for 5 hours
  6. concentrationThe reaction mixture is concentrated in vacuo
  7. custompartitioned between water and chloroform
  8. dry with materialThe organic layer is dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue is purified by flash column chromatography
  12. washeluting with 1:1 hexane
  13. additionThe fractions containing product
  14. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-6dac570b77a445c1b612d6f3d2614f00
출처 데이터셋
uspto-grants-2007_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07276519B2

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