Lithium Hexamethyldisilazide → 8-cyclopentyl-6-(2-ethoxy-ethyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 586527Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 586527
C(O[C:4](=[O:11])[CH2:5][CH2:6][CH2:7][O:8][CH2:9][CH3:10])C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:22]1([NH:27][C:28]2[C:33]([CH:34]=O)=[CH:32][N:31]=[C:30]([S:36][CH3:37])[N:29]=2)[CH2:26][CH2:25][CH2:24][CH2:23]1>C1COCC1>[CH:22]1([N:27]2[C:28]3[N:29]=[C:30]([S:36][CH3:37])[N:31]=[CH:32][C:33]=3[CH:34]=[C:5]([CH2:6][CH2:7][O:8][CH2:9][CH3:10])[C:4]2=[O:11])[CH2:23][CH2:24][CH2:25][CH2:26]1

Komponenten

5

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 4424983Ethyl 4-ethoxybutyrateHCID 107998964-(Cyclopentylamino)-2-(methylthio)pyrimidine-5-carbaldehyde

Produkt 1

HCID 114390248-cyclopentyl-6-(2-ethoxy-ethyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a cooled (−78° C.) solution of 4-ethoxy-butyric acid ethyl ester (9.85 g, 61.47 mmol) in THF (25 ml) was added lithium bis(trimethylsilyl)amide (77.0 ml, 76.85 mmol, 1 M solution in THF). The reaction mixture was stirred for 10 minutes to form the anion. 4-Cyclopentylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde was then added and the reaction allowed to warm to RT and stirred overnight. The reaction mixture was quenched with 10% aqueous HCl (100 ml). The aqueous layer was extracted with ethylacetate (150 ml total) and the organic layers were combined and concentrated to give a yellow oil. Chromatographic purification on silica gel (chloroform/ethyl acetate gradient) gave 8-cyclopentyl-6-(2-ethoxy-ethyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (3.22 g, 9.65 mmol). MS (APCI+) 334 (M+1, 100); 1H NMR δ (400 MHz, DMSO-d6) 8.54 (s, 1H), 7.47-7.46 (m, 1H), 5.99-5.90 (m, 1H), 3.69 (t, J=6.25 Hz, 2H), 3.49 (q, J=7.03 Hz, 2H), 2.84 (t, J=6.25 Hz, 2H), 2.59 (s, 3H), 2.34-2.29 (m, 2H), 2.08-2.02 (m, 2H), 1.88-1.83 (m, 2H), 1.69-1.65 (m, 3H), 1.17 (t, J=7.04 Hz, 3H).

Aufarbeitung

  1. customto form the anion
  2. stirringstirred overnight
  3. customThe reaction mixture was quenched with 10% aqueous HCl (100 ml)
  4. extractionThe aqueous layer was extracted with ethylacetate (150 ml total)
  5. concentrationconcentrated
  6. customto give a yellow oil
  7. customChromatographic purification on silica gel (chloroform/ethyl acetate gradient)

Quellen und Nachweise

ORD-Eintrag
ord-b002fb2bad61435ba636f95bb0b9613b
Quelldatensatz
uspto-grants-2005_08
Patentnummer
US06936612B2

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