Triethylamine → N-[(4-Amino-1-isobutyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-2-yl)methyl]-N-methoxycyclopropanecarboxamide

HRID 2426369ノート

反応式

HRID 2426369 の反応式
[CH2:1]([N:5]1[C:13]2[C:12]([CH3:14])=[C:11]([CH3:15])[N:10]=[C:9]([NH2:16])[C:8]=2[N:7]=[C:6]1[CH2:17][NH:18][O:19][CH3:20])[CH:2]([CH3:4])[CH3:3].C(N(CC)CC)C.[CH:28]1([C:31](Cl)=[O:32])[CH2:30][CH2:29]1>ClCCl.C1(C(Cl)=O)CC1>[NH2:16][C:9]1[C:8]2[N:7]=[C:6]([CH2:17][N:18]([O:19][CH3:20])[C:31]([CH:28]3[CH2:30][CH2:29]3)=[O:32])[N:5]([CH2:1][CH:2]([CH3:4])[CH3:3])[C:13]=2[C:12]([CH3:14])=[C:11]([CH3:15])[N:10]=1

参加物

6

反応物 3

HCID 8471Triethylamine2 回HCID 77637Cyclopropanecarbonyl chloride2 回HCID 119562431-isobutyl-2-[(methoxyamino)methyl]-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine

生成物 1

HCID 11956245N-[(4-Amino-1-isobutyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-2-yl)methyl]-N-methoxycyclopropanecarboxamide収率 44.3%

試薬・触媒・溶媒 2

HCID 77637Cyclopropanecarbonyl chloride触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
-5 °C

実験手順

Under a nitrogen atmosphere, 1-isobutyl-2-[(methoxyamino)methyl]-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine (0.53 g, 1.91 mmol) was dissolved in dichloromethane (19 mL) and cooled to −5° C. Triethylamine (293 uL, 2.10 mmol) was added followed by dropwise addition of cyclopropane carbonyl chloride (173 uL, 1.91 mmol). The solution was allowed to stir at RT for 2 hours, then cooled back to −5° C. More triethylamine (38 uL, 0.27 mmol) and cyclopropane carbonyl chloride (23 uL, 0.25 mmol) were added and the reaction was allowed to stir at 0° C. for 45 minutes. More cyclopropane carbonyl chloride (5 uL, 0.06 mmol) was added and stirring continued for another 30 minutes. Dichloromethane (100 mL) was added and the solution was washed successively with saturated aqueous sodium bicarbonate (30 mL), water (3×25 mL), and brine (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by HPFC eluting with a gradient of 0-35% CMA in chloroform and then recrystallized from ethyl acetate/hexanes to provide 292 mg of pure product as an off-white powder, mp 135.0-137.0° C. Anal. Calcd for C18H27N5O2 C, 62.59; H, 7.88; N, 20.27. Found: C, 62.68; H, 7.82; N, 19.93.

後処理

  1. temperaturecooled back to −5° C
  2. stirringto stir at 0° C. for 45 minutes
  3. stirringstirring
  4. waitcontinued for another 30 minutes
  5. washthe solution was washed successively with saturated aqueous sodium bicarbonate (30 mL), water (3×25 mL), and brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by HPFC
  10. washeluting with a gradient of 0-35% CMA in chloroform
  11. customrecrystallized from ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-e2641039fa064fdea75fd6be3662503e
出典データセット
uspto-grants-2011_06
特許番号
US07968563B2

反応ノート

読み込み中…