Chloroacetyl chloride → N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide

HRID 1694584ノート

反応式

HRID 1694584 の反応式
[Cl:1][CH2:2][C:3](Cl)=[O:4].[Br:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11]([NH:18][CH2:19][CH:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[C:12]([NH2:17])[CH:13]=[N:14]2)=[CH:9][CH:8]=1>ClCCl>[Br:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11]([NH:18][CH2:19][CH:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)=[C:12]([NH:17][C:3](=[O:4])[CH2:2][Cl:1])[CH:13]=[N:14]2)=[CH:9][CH:8]=1

参加物

4

反応物 2

HCID 6577Chloroacetyl chloride2 回HCID 688209287-bromo-N4-(tetrahydro-2H-pyran-4-ylmethyl)quinoline-3,4-diamine

生成物 1

HCID 67280759N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide収率 44.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

Chloroacetyl chloride (5.2 mL, 65 mmol) was added to 7-bromo-N4-(tetrahydro-2H-pyran-4-ylmethyl)quinoline-3,4-diamine (55 mmol) dissolved in 273 mL of dichloromethane at 0° C. A solid formed after adding half of the chloroacetyl chloride at which point additional dichloromethane (100 mL) was added. The reaction was stirred for 1 hour at ambient temperature. The yellow suspension was quenched first with aqueous saturated sodium bicarbonate followed by 50% aqueous sodium hydroxide until a pH of 14 was reached. Filtration provided 10 g of N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide as a tan solid. The filtrate was placed in a separatory funnel and the layers were separated. The aqueous layer was extracted with additional dichloromethane. The combined organic extracts were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford additional N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide as a yellow oil. The yellow oil was carried forward without further purification assuming a 50% yield (27.3 mmol). The oil was combined with ethanol (100 mL) and triethylamine (7.5 mL, 54 mmol). The resulting yellow solution was refluxed for 2 hours. The reaction was cooled to ambient temperature and the solvent was removed under reduced pressure to provide 7-bromo-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline as a brown oil that was used without further purification assuming quantitative yield.

後処理

  1. customA solid formed
  2. additionwas added
  3. customThe yellow suspension was quenched first with aqueous saturated sodium bicarbonate
  4. filtrationFiltration

出典と根拠

ORDレコード
ord-c8ecb9ba1c8044f6b2424f354dfcf401
出典データセット
uspto-grants-2012_04
特許番号
US08158794B2

反応ノート

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