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

HRID 1369434ノート

反応式

HRID 1369434 の反応式
[Cl:1][C:2]1[N:3]=[N:4][C:5]([NH:12][NH:13][C:14](=O)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])=[CH:6][C:7]=1[Si:8]([CH3:11])([CH3:10])[CH3:9].BrC(Cl)(Cl)C(Cl)(Cl)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>C(#N)C.ClCCl>[Cl:1][C:2]1[C:7]([Si:8]([CH3:11])([CH3:10])[CH3:9])=[CH:6][C:5]2[N:4]([C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[F:21])=[N:13][N:12]=2)[N:3]=1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 694261,2-Dibromo-1,1,2,2-tetrachloroethaneHCID 15486174N'-(6-Chloro-5-(trimethylsilyl)pyridazin-3-yl)-2-fluorobenzohydrazide

生成物 1

HCID 154861756-Chloro-3-(2-fluorophenyl)-7-(trimethylsilyl)-[1,2,4]triazolo[4,3-b]pyridazine収率 83.3%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
1 °C

実験手順

To a stirred suspension of 3-chloro-6-[2-(2-fluorobenzoyl)hydrazino]-4-(trimethylsilyl)pyridazine (9.72 g, 28.7 mmol) and 1,2-dibromotetrachloroethane (18.68 g, 57.4 mmol) in anhydrous acetonitrile (170 ml), cooled under nitrogen to 1° C., was added portionwise, over 21 min, solid triphenylphosphine (30.10 g, 115 mmol), keeping the temperature below 5° C. The mixture was stirred at 2° C. for 10 min, then anhydrous triethylamine (32.0 ml, 230 mmol) was added dropwise over 18 min, keeping the temperature below 6° C. The mixture was then stirred at 0-3° C. under nitrogen for 85 min. The mixture was then diluted with dichloromethane (150 ml) and washed with water (200 ml). The organic layer was dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 20-40% EtOAc/hexane) to afford 7.67 g (83%) of the title compound as a white solid; 1H NMR (360 MHz, CDCl3) δ0.48 (9H, s), 7.30 (1H. dd, Jd=10.1 and 8.8 Hz), 7.36 (1H. td, J=7.6 and 1.1 Hz), 7.58 (1H, m). 7.90 (1H, td. J=7.3 and 1.8 Hz), 8.30 (1H, s); MS (ES+) m/e 321/323 [MH]+.

後処理

  1. additionwas added portionwise, over 21 min
  2. customthe temperature below 5° C
  3. customthe temperature below 6° C
  4. stirringThe mixture was then stirred at 0-3° C. under nitrogen for 85 min
  5. washwashed with water (200 ml)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash chromatography (silica gel, 20-40% EtOAc/hexane)

出典と根拠

ORDレコード
ord-c58552c8d08641668f8982050cf90adc
出典データセット
uspto-grants-2003_06
特許番号
US06579875B1

反応ノート

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