Methyl vinyl ketone → Rac-9-(4-fluorophenyl)-3-oxo-1,2,3,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile

HRID 718772Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 718772
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]4[C:21]([C:22]#[N:23])=[C:20](O)[CH2:19][CH2:18][CH2:17][C:14]=4[CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:25][C:26](=[O:29])[CH:27]=[CH2:28]>CCO.CC1C=CC(S(O)(=O)=O)=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C:20]5[C:21]([C:22]#[N:23])([CH2:28][CH2:27][C:26](=[O:29])[CH:25]=5)[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Komponenten

5

Edukt 2

HCID 6570Methyl vinyl ketoneHCID 867223551-(4-Fluorophenyl)-6-hydroxy-1,7,8,9-tetrahydrocyclohepta[f]indazole-5-carbonitrile

Produkt 1

HCID 86722360Rac-9-(4-fluorophenyl)-3-oxo-1,2,3,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrileAusbeute 80,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6101p-Toluenesulfonic acidKatalysatorHCID 702EthanolLösungsmittel

Versuchsvorschrift

A solution of 1-(4-fluorophenyl)-6-hydroxy-1,7,8,9-tetrahydrocyclohepta[f]indazole-5-carbonitrile (29, R1=4-Fluorophenyl) (30.0 g, 94 mmol) in EtOH (640 mL) was treated with TEA (3.93 mL, 28.2 mmol) and but-3-en-2-one (15.5 mL, 188 mmol) and the mixture was stirred mechanically at rt for about 18 h. The volume of the reaction was reduced to about 300 mL under reduced pressure and the intermediate was filtered off and washed with heptane (50 mL). The solid intermediate is taken up in toluene (1500 mL), treated with pTSA (0.894 g, 4.70 mmol) and heated at reflux with a Dean-Stark trap for about 5 h, then stirred at about 90° C. for about 16 h. The reaction was cooled to rt, washed with sat. aq. NaHCO3 (300 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield rac-9-(4-fluorophenyl)-3-oxo-1,2,3,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile (30, R1=4-Fluorophenyl) (28.0 g, 72%) as a tan foam. LC/MS, method 3, Rt=2.42 min, 1H NMR (400 MHz, DMSO) δ 8.45 (d, J=0.9 Hz, 1H), 8.20 (s, 1H), 7.84-7.78 (m, 2H), 7.69 (s, 1H), 7.48-7.39 (m, 2H), 6.18 (s, 1H), 3.01-2.59 (m, 6H), 2.46-2.37 (m, 1H), 2.24-2.12 (m, 1H), 2.02-1.87 (m, 2H).

Aufarbeitung

  1. filtrationthe intermediate was filtered off
  2. washwashed with heptane (50 mL)
  3. temperatureheated
  4. temperatureat reflux with a Dean-Stark trap for about 5 h
  5. stirringstirred at about 90° C. for about 16 h
  6. temperatureThe reaction was cooled to rt
  7. washwashed with sat. aq. NaHCO3 (300 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-fe1bd7fc699540c692835dd86f79dd70
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193744B2

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