5-Bromopyridine-2,3-diamine → HCID 178519518, Verbindung

HRID 499179

Reaktionsgleichung

Reaktionsgleichung von HRID 499179
[Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[N:6][CH:7]=1.[F:10][C:11]([F:36])([F:35])[C:12]1[CH:34]=[CH:33][CH:32]=[CH:31][C:13]=1[C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[N:27]=[N:26][C:25]([C:28](O)=O)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1)=[O:15]>O=P(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[N:9]=[C:28]([C:25]3[N:26]=[N:27][C:22]([N:19]4[CH2:18][CH2:17][N:16]([C:14]([C:13]5[CH:31]=[CH:32][CH:33]=[CH:34][C:12]=5[C:11]([F:36])([F:10])[F:35])=[O:15])[CH2:21][CH2:20]4)=[CH:23][CH:24]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Komponenten

4

Edukt 2

HCID 6911565-Bromopyridine-2,3-diamineHCID 454873706-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid

Produkt 1

HCID 178519518HCID 178519518, VerbindungAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 24813Phosphorus oxychlorideLösungsmittel

Reaktionsbedingungen

Temperatur
12.5 °C

Versuchsvorschrift

A mixture of 5-bromopyridine-2,3-diamine (0.188 g, 1.000 mmol) and 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (0.380 g, 1.000 mmol) in POCl3 (7 mL) was heated to reflux for 24 hours. The solvent was evaporated in vacuo, and the dark residue was neutralized with ice-cold NaOH solution. The mixture was extracted with ethyl acetate. The organic layer was separated, dried over MgSO4 and filtered through the short pad of silica gel. The filtrate was concentrated, ether was added. After cooling to 10-15° C. the white precipitation started to form. This was filtered off and dried in vacuo to yield {4-[6-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)pyridazin-3-yl]piperazin-1-yl}-(2-trifluoromethylphenyl)methanone in 74% yield (0.394 g, 0.810 mmol). 1H NMR (300 MHz, CDCl3) δ 13.64 (br., s, 1H), 8.40 (s, 1H), 8.17 (d, J=9.6 Hz, 1H), 8.03 (br, s, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.76 (t, J=7.4 Hz, 1H), 7.65 (t, J=7.5 Hz, 1H), 7.43 (d, J=9.6 Hz, 1H), 3.90-3.20 (m, 8H13C NMR (75 MHz, CDCl3) δ 166.8, 159.9, 152.8, 144.9, 143.5, 135.0, 133.4, 130.1, 128.0, 127.1, 127.0, 126.9, 126.0, 125.9, 125.6, 122.4, 113.8, 46.4, 44.5, 44.3, 41.2. MS (ES+) m/z 532, 534 (M+1).

Aufarbeitung

  1. temperaturewas heated
  2. temperatureto reflux for 24 hours
  3. customThe solvent was evaporated in vacuo
  4. extractionThe mixture was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered through the short pad of silica gel
  8. concentrationThe filtrate was concentrated
  9. additionether was added
  10. customthe white precipitation
  11. customto form
  12. filtrationThis was filtered off
  13. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-2ba4e1346fb04317bf9b9a43d7afcdab
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07767677B2

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