N,N-Dimethylaniline → Methyl 2-(4-chloro-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate

HRID 1399698

反応式

HRID 1399698 の反応式
[CH3:1][C:2]1[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[NH:5][C:6](=O)[C:7]=1[CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10].P(Cl)(Cl)([Cl:25])=O.CN(C)C1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:25][C:6]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:2]([CH3:1])[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[N:5]=1

参加物

5

反応物 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 136346161Methyl 2-(4-methyl-6-oxo-2-(piperidin-1-yl)-1,6-dihydropyrimidin-5-yl)pentanoate

生成物 1

HCID 86665653Methyl 2-(4-chloro-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate収率 39%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

To a suspension of methyl 2-(4-methyl-6-oxo-2-(piperidin-1-yl)-1,6-dihydropyrimidin-5-yl)pentanoate (5.97 g; 19.42 mmol) in dry toluene (40 mL) under nitrogen atmosphere were carefully added phosphorus oxychloride (18.05 mL; 194 mmol) and dimethylaniline (1.961 mL, 15.54 mmol). The reaction was heated to reflux for 3 h and after cooling at room temperature, the volatiles were removed under reduced pressure and the remaining residue was cooled in an ice-bath and quenched by adding crushed ice and a saturated solution of sodium hydrogen carbonate until neutralization. The product was extracted twice with ethyl acetate and the combined organic layers were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (1-10%) in heptane furnished 2.45g (39%) of the title compound as a yellow oil.

後処理

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 3 h
  3. customthe volatiles were removed under reduced pressure
  4. temperaturethe remaining residue was cooled in an ice-bath
  5. customquenched
  6. additionby adding
  7. customcrushed ice
  8. extractionThe product was extracted twice with ethyl acetate
  9. dry with materialthe combined organic layers were dried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (1-10%) in heptane

出典と根拠

ORDレコード
ord-dce1587137ea4d09a53630f3ee4023b5
出典データセット
uspto-grants-2014_12
特許番号
US08906906B2

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