Diethyl chlorophosphate → 5-cyano-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo [2,3-b]pyridin-3-yl)pyrimidin-2-yl diethyl phosphate

HRID 40845

反応式

HRID 40845 の反応式
[OH:1][C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([C:17]([F:20])([F:19])[F:18])[CH:15]=3)[N:10]([S:21]([C:24]3[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:9]=2)[C:5]([C:31]#[N:32])=[CH:4][N:3]=1.CC(C)([O-])C.[K+].[CH2:39]([O:41][P:42](Cl)([O:44][CH2:45][CH3:46])=[O:43])[CH3:40].C([O-])(O)=O.[Na+]>C1COCC1>[P:42]([O:44][CH2:45][CH3:46])([O:41][CH2:39][CH3:40])([O:1][C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([C:17]([F:18])([F:20])[F:19])[CH:15]=3)[N:10]([S:21]([C:24]3[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:9]=2)[C:5]([C:31]#[N:32])=[CH:4][N:3]=1)=[O:43]

参加物

6

反応物 4

HCID 13139Diethyl chlorophosphateHCID 516892Sodium BicarbonateHCID 23665647Potassium tert-butoxideHCID 178427354HCID 178427354、化合物

生成物 1

HCID 594143445-cyano-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo [2,3-b]pyridin-3-yl)pyrimidin-2-yl diethyl phosphate収率 58.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

2-hydroxy-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (87% pure, 1.23 g, 2.329 mmol) in dry THF (24.60 mL) was stirred at −25° C. and treated with potassium t-butoxide (2.795 mL of 1.0 M, 2.795 mmol) in THF. The reaction mixture was warmed up to 0° C. for 20 minutes, cooled to −50° C. and treated with diethylchlorophosphate (482.3 mg, 403.9 μL, 2.795 mmol). The reaction mixture was stirred at −40° C. for 20 minutes and at room temperature for 2 hours. The reaction mixture was diluted with ice cold ethyl acetate (60 mL), cooled in ice and shaken quickly with ice cold water containing 1M HCl (2.8 mL, 2.8 mmol), basified with aqueous NaHCO3 and extracted into ethyl acetate. The organic extracts were dried over magnesium sulfate and concentrated to give a pale yellow solid which was triturated with ether and filtered to give a pale yellow solid (810 mg). The mother liquors were concentrated in vacuo and the residue purified on silica gel by flash column chromatography to afford a colourless solid (219 mg) (total: 1.029 g, 74% yield).

後処理

  1. temperaturecooled to −50° C.
  2. temperaturecooled in ice
  3. extractionextracted into ethyl acetate
  4. dry with materialThe organic extracts were dried over magnesium sulfate
  5. concentrationconcentrated
  6. customto give a pale yellow solid which
  7. customwas triturated with ether
  8. filtrationfiltered

出典と根拠

ORDレコード
ord-814f531bbd464f5c8a7e1f6f6a067205
出典データセット
uspto-grants-2013_09
特許番号
US08530489B2

関連ノート

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