Cyclobutanone → 6-Chloro-3-(2-fluorophenyl)-7-(1-hydroxycyclobutyl)-1,2,4-triazolo[4,3-b]pyridazine

HRID 2306594

反応式

HRID 2306594 の反応式
[Cl:1][C:2]1[C:3]([Si](C)(C)C)=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])=[N:9][N:10]=2)[N:7]=1.[C:22]1(=[O:26])[CH2:25][CH2:24][CH2:23]1>C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.C1C=CC([Sn-](F)(F)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:3]([C:22]2([OH:26])[CH2:25][CH2:24][CH2:23]2)=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])=[N:9][N:10]=2)[N:7]=1

参加物

5

反応物 2

HCID 14496CyclobutanoneHCID 154861756-Chloro-3-(2-fluorophenyl)-7-(trimethylsilyl)-[1,2,4]triazolo[4,3-b]pyridazine

生成物 1

HCID 226099106-Chloro-3-(2-fluorophenyl)-7-(1-hydroxycyclobutyl)-1,2,4-triazolo[4,3-b]pyridazine収率 26%

試薬・触媒・溶媒 2

HCID 1784490421-Butanaminium, N,N,N-tributyl-, (TB-5-11)-difluorotriphenylstannate(1-) (1:1)触媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred solution of 6-chloro-3-(2-fluorophenyl)-7-(trimethylsilyl)-1,2,4-triazolo[4,3-b]pyridazine (1.04 g, 3.24 mmol) in anhydrous THF (15 ml) under nitrogen was added cyclobutanone (1.21 ml, 16.2 mmol), followed by solid tetrabutylammonium difluorotriphenylstannate (0.410 g, 0.650 mmol). The flask was evaporated and refilled with nitrogen four times, then stirred at room temperature for 5.75 h. More tetrabutylammonium difluorotriphenylstannate (0.403 g, 0.639 mmol) was added and the mixture was stirred for a further 36 h. The mixture was then partitioned between dichloromethane (75 ml) and water (75 ml). The aqueous layer was extracted further with dichloromethane (2×50 ml), and the combined organic extracts were dried (Na2SO4) and evaporated ill vacuo. The residue was purified by flash chromatography (silica gel, 70-100% EtOAc/hexane) to give 0.2634 g (26%) of the title compound as a cream solid; 1H NMR (360 MHz, CDCl3) δ 1.81 (1H, m), 2.27 (1H, m), 2.52 (2H, m), 2.72 (2H, m), 2.87 (1H, s), 7.30 (1H, t, J=9.3 Hz), 7.36 (1H, t, J=7.5 Hz), 7.58 (1H, m), 7.88 (1H, td, J=7.3 and 1.8 Hz), 8.12 (1H, s); MS (ES+) m/e 319/321 [MH]+, 249.

後処理

  1. customThe flask was evaporated
  2. additionrefilled with nitrogen four times
  3. stirringthe mixture was stirred for a further 36 h
  4. customThe mixture was then partitioned between dichloromethane (75 ml) and water (75 ml)
  5. extractionThe aqueous layer was extracted further with dichloromethane (2×50 ml)
  6. dry with materialthe combined organic extracts were dried (Na2SO4)
  7. customevaporated ill vacuo
  8. customThe residue was purified by flash chromatography (silica gel, 70-100% EtOAc/hexane)

出典と根拠

ORDレコード
ord-3bf14e550ea24def86ffb5e271048168
出典データセット
uspto-grants-2004_12
特許番号
US06828322B2

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