Dihydropyrimidine → Boc piperidine dihydropyrimidine

HRID 1374689Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1374689
[C:1]([N:8]1[CH2:13][CH2:12][CH:11](CBr)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].C(OC([C:24]1[CH:25](C2C=CC=C(Cl)C=2)[N:26]=[C:27](OC)[NH:28][C:29]=1C)=O)(C)C.N1CCCCC1.N1C=CC=NC1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[NH:28]1[CH:29]=[CH:24][CH:25]=[N:26][CH2:27]1.[C:1]([N:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Komponenten

8

Edukt 5

HCID 1056DihydropyrimidineHCID 8082PiperidineHCID 24758Sodium hydrideHCID 148017422-Methoxy-6-methyl-4-(3-chloro-phenyl)-1,4-dihydro-pyrimidine-5-carboxylic acid isopropyl esterHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylate

Produkt 1

HCID 86596649Boc piperidine dihydropyrimidineAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

Tetrabutyl ammonium iodide (0.39 mmol) was added to a solution of N-Boc 4-bromomethyl piperidine (0.58 mmol; prepared as described in Bioorganic and Medicinal Chemistry Letters, 9, 2615, (1999)) in dimethylformamide (1 ml) at ambient temperature for 20 minutes. In a second vessel, NaH (0.47 mmol) was added to a solution of 2-methoxy-6-methyl-4-(3-chloro-phenyl)-1,4-dihydro-pyrimidine-5-carboxylic acid isopropyl ester (0.39 mmol) in dimethylformamide (1 ml) at ambient temperature and stirred for 20 minutes. The piperidine solution was then added to the dihydropyrimidine solution and stirred for approximately 2 hours. The reaction was quenched by addition of water, diluted with ethyl acetate, and subsequently washed with water and brine solution. The acetate layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting material was purified via silica gel chromatography utilizing 20% ethyl acetate/hexanes eluent affording the corresponding N Boc piperidine dihydropyrimidine intermediate 195A in 29% yield.

Aufarbeitung

  1. stirringstirred for approximately 2 hours
  2. customThe reaction was quenched by addition of water
  3. additiondiluted with ethyl acetate
  4. washsubsequently washed with water and brine solution
  5. dry with materialThe acetate layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting material was purified via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-eea2b5cbb7f943a5b718ebdf7413e211
Quelldatensatz
uspto-grants-2007_01
Patentnummer
US07166603B2

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