1-Butanol → (R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-nitroimidazo[1,2-b]pyridazine

HRID 2096291ノート

反応式

HRID 2096291 の反応式
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([N+:11]([O-:13])=[O:12])=[CH:9][N:10]=2)[N:7]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[C@H:22]1[CH2:26][CH2:25][CH2:24][NH:23]1.C(O)CCC>CCOC(C)=O>[F:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[C@H:22]1[CH2:26][CH2:25][CH2:24][N:23]1[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([N+:11]([O-:13])=[O:12])=[CH:9][N:10]=2)[N:7]=1

参加物

5

反応物 3

HCID 2631-ButanolHCID 71762902-(2,5-Difluorophenyl)pyrrolidine, (R)-HCID 105359816-Chloro-3-nitro-imidazo(1,2-b)pyridazine

生成物 1

HCID 67307105(R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-nitroimidazo[1,2-b]pyridazine収率 75.3%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
140 °C

実験手順

A suspension of 6-chloro-3-nitroimidazo[1,2-b]pyridazine (1.0 g, 5.0 mmol) and (R)-2-(2,5-difluorophenyl)pyrrolidine (Prepared as described in Preparation A; 1.9 g, 11 mmol) in n-butanol (4.6 mL, 50 mmol) was sealed in a pressure reaction tube and stirred in a 140° C. oil bath overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc (250 mL), then washed with water (2×150 mL) and brine (150 mL), filtered through a Biotage Phase Separator filter paper and concentrated. The crude material was purified by silica gel chromatography, eluting with 2:1 EtOAc/hexanes to yield the product as a foamy yellow powder (1.3 g, 75% yield).

後処理

  1. customwas sealed in a pressure reaction tube
  2. temperatureAfter cooling to ambient temperature
  3. washwashed with water (2×150 mL) and brine (150 mL)
  4. filtrationfiltered through a Biotage Phase Separator
  5. filtrationfilter paper
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting with 2:1 EtOAc/hexanes

出典と根拠

ORDレコード
ord-d88801aafbd64e9ca594f077bd474ba2
出典データセット
uspto-grants-2013_05
特許番号
US08450322B2

反応ノート

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