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 718772ノート

反応式

HRID 718772 の反応式
[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

参加物

5

反応物 2

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

生成物 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-carbonitrile収率 80.2%

試薬・触媒・溶媒 2

HCID 6101p-Toluenesulfonic acid触媒HCID 702Ethanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-fe1bd7fc699540c692835dd86f79dd70
出典データセット
uspto-grants-2015_11
特許番号
US09193744B2

反応ノート

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