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

HRID 1399698

반응식

HRID 1399698 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-dce1587137ea4d09a53630f3ee4023b5
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906906B2

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