Iodoethane → 6-Amino-7-ethyl-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-7,9-dihydro-8H-purin-8-one

HRID 510105ノート

反応式

HRID 510105 の反応式
[F:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][C:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[N:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([NH2:21])=[C:16]([NH2:22])[N:15]=2)[N:6]=1.I[CH2:28][CH3:29].[O:30]1CCC[CH2:31]1>C(OCC)(=O)C>[NH2:20][C:18]1[N:19]=[C:14]([N:7]2[C:8]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[C:5]([CH2:4][C:3]3[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=3[F:1])=[N:6]2)[N:15]=[C:16]2[C:17]=1[N:21]([CH2:28][CH3:29])[C:31](=[O:30])[NH:22]2

参加物

5

反応物 3

HCID 6340IodoethaneHCID 8028TetrahydrofuranHCID 24794429HCID 24794429、化合物

生成物 1

HCID 666139886-Amino-7-ethyl-2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]-7,9-dihydro-8H-purin-8-one

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

200 mg (0.392 mmol) of 2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,5,6-triamine (example 2A) were initially charged in tetrahydrofuran (11.1 ml) and the suspension was cooled to 0° C. Subsequently, 0.43 ml (0.43 mmol) of bis(trimethylsilyl)sodium amide solution (1.0 M in tetrahydrofuran) was added and the mixture was stirred at 0° C. for a further 30 min Thereafter, 31.3 μl (0.392 mmol) of iodoethane were added dropwise and the reaction mixture was stirred at RT overnight. The reaction mixture was cooled again to 0° C. and a further 0.47 ml (0.47 mmol) of bis(trimethylsilyl)sodium amide solution was added. Thereafter, the reaction mixture was stirred at RT overnight and heated to reflux for a further 2 days. Subsequently, the reaction mixture was diluted with ethyl acetate and washed twice with saturated aqueous sodium hydrogencarbonate solution. The organic phase was dried over magnesium sulfate, filtered and concentrated by rotary evaporation. The residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient) and the product fractions were concentrated. The crude product was extracted by stirring in methyl tert-butyl ether, and the solids were filtered off and dried under high vacuum. This gave 4.6 mg (2.9% of theory) of the title compound in solid form.

後処理

  1. stirringthe reaction mixture was stirred at RT overnight
  2. temperatureThe reaction mixture was cooled again to 0° C.
  3. stirringThereafter, the reaction mixture was stirred at RT overnight
  4. temperatureheated
  5. temperatureto reflux for a further 2 days
  6. washwashed twice with saturated aqueous sodium hydrogencarbonate solution
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation
  10. customThe residue was separated by means of preparative HPLC (eluent: acetonitrile-water with 0.1% formic acid gradient)
  11. concentrationthe product fractions were concentrated
  12. extractionThe crude product was extracted
  13. stirringby stirring in methyl tert-butyl ether
  14. filtrationthe solids were filtered off
  15. customdried under high vacuum

出典と根拠

ORDレコード
ord-1a547e7b188f493ea8a6a50afdd5dcee
出典データセット
uspto-grants-2015_08
特許番号
US09096592B2

反応ノート

読み込み中…