Cyclobutanol → Cyclobutyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}carbamate

HRID 626617ノート

反応式

HRID 626617 の反応式
[CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.ClC(O[C:11](=[O:17])OC(Cl)(Cl)Cl)(Cl)Cl.[F:18][C:19]1[CH:20]=[C:21]2[N:27]([C:28]3[N:33]=[C:32]([NH2:34])[C:31]([NH2:35])=[C:30]([NH2:36])[N:29]=3)[N:26]=[C:25]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[F:44])[C:22]2=[N:23][CH:24]=1.C(=O)(O)[O-].[Na+]>ClCCl.N1C=CC=CC=1>[NH2:36][C:30]1[C:31]([NH:35][C:11](=[O:17])[O:5][CH:1]2[CH2:4][CH2:3][CH2:2]2)=[C:32]([NH2:34])[N:33]=[C:28]([N:27]2[C:21]3[C:22](=[N:23][CH:24]=[C:19]([F:18])[CH:20]=3)[C:25]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[F:44])=[N:26]2)[N:29]=1

参加物

7

反応物 4

HCID 76218CyclobutanolHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 675168882-[6-Fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,5,6-triamine

生成物 1

HCID 57335162Cyclobutyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}carbamate

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒2 回HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

Under argon, 64 ml (0.81 mmol) of cyclobutyl alcohol were initially charged in dichloromethane (4.1 ml), 161 mg (0.54 mmol) of bis(trichloromethyl)carbonate were then added and the mixture was cooled to 0° C. 53 μl (0.65 mmol) of pyridine were then added dropwise, and the reaction mixture was stirred at 0° C. for another 30 min. 200 mg (0.54 mmol) of the compound from example 6A were then added, and the mixture was diluted with 1.4 ml of pyridine. The reaction mixture was stirred at RT overnight, saturated aqueous sodium bicarbonate solution was then added and the mixture was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was purified by means of preparative RP-HPLC (acetonitrile:water (+0.1% formic acid)−gradient) and the product fractions were concentrated.

後処理

  1. stirringThe reaction mixture was stirred at RT overnight
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by means of preparative RP-HPLC (acetonitrile:water (+0.1% formic acid)−gradient)
  7. concentrationthe product fractions were concentrated

出典と根拠

ORDレコード
ord-dc931a180c9b472da37bd63639b63231
出典データセット
uspto-grants-2016_04
特許番号
US09309239B2

反応ノート

読み込み中…