4-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[2,3-b]pyridine-5-carbonitrile → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[3-(4-methylpiperazin-1-yl)prop-1-ynyl]thieno[2,3-b]pyridine-5-carbonitrile

HRID 1611547Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1611547
[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[S:20][C:21](I)=[CH:22][C:13]=12.[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]#[CH:33])[CH2:27][CH2:26]1>C1C=CC=CC=1.C(N(CC)CC)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu](I)I>[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[S:20][C:21]([C:33]#[C:32][CH2:31][N:28]3[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]3)=[CH:22][C:13]=12

Komponenten

7

Edukt 2

HCID 102543834-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-iodothieno[2,3-b]pyridine-5-carbonitrileHCID 135140911-Methyl-4-(prop-2-yn-1-yl)piperazine

Produkt 1

HCID 100968994-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[3-(4-methylpiperazin-1-yl)prop-1-ynyl]thieno[2,3-b]pyridine-5-carbonitrileAusbeute 66,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 83717Copper iodideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 241BenzeneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

A mixture of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-2-iodothieno[2,3-b]pyridine-5-carbonitrile (160 mg, 0.34 mmol), 1-methyl-4-prop-2-ynyl-piperazine (70 mg, 0.5 mmol), 15 mg of tetrakis(triphenylphosphine)palladium(0) and copper iodide (8 mg, 0.016 mmol) in 7 mL of benzene and 2 mL of triethylamine is heated at reflux for 7 hours. The reaction mixture is cooled to room temperature and partitioned between water and dichloromethane. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is triturated with ether and hexanes to provide 110 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[3-(4-methylpiperazin-1-yl)prop-1-ynyl]thieno[2,3-b]pyridine-5-carbonitrile as an off white solid, mp 175° C. (decomposition); 1H NMR (DMSO-d6) δ 2.17 (s, 3H), 2.37 (bs, 4H), 2.54 (bs, 4H), 3.62 (s, 2H), 3.85 (s, 3H), 7.38 (s, 1H), 7.76 (s, 1H), 7.91 (s, 1H), 8.47 (bs, 1H), 9.83 (bs, 1H); MS 486.2 (M+H)+.

Aufarbeitung

  1. temperatureis heated
  2. temperatureat reflux for 7 hours
  3. custompartitioned between water and dichloromethane
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is triturated with ether and hexanes

Quellen und Nachweise

ORD-Eintrag
ord-921c8f6d22ad4686a20ae5f9f16ec893
Quelldatensatz
uspto-grants-2006_01
Patentnummer
US06987116B2

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