N-methyl-2-pyrrolidone → HCID 67112014, Verbindung

HRID 2088903Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2088903
Cl[C:2]1[C:3]2[CH:11]([CH3:12])[CH2:10][C:9](=[O:13])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.Cl.Cl.Cl.[N:17]1([CH2:22][CH2:23][N:24]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[N:26]=[C:25]2[CH:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH2:21][CH2:20][CH2:19][CH2:18]1.CN1CCCC1=O.C(N(C(C)C)CC)(C)C>O>[CH3:12][CH:11]1[C:3]2[C:2]([N:36]3[CH2:35][CH2:34][CH:33]([C:25]4[N:24]([CH2:23][CH2:22][N:17]5[CH2:18][CH2:19][CH2:20][CH2:21]5)[CH:28]=[C:27]([C:29]([F:31])([F:32])[F:30])[N:26]=4)[CH2:38][CH2:37]3)=[N:7][CH:6]=[N:5][C:4]=2[NH:8][C:9](=[O:13])[CH2:10]1

Komponenten

6

Edukt 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 866665664-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneHCID 866665764-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidine trihydrochloride

Produkt 1

HCID 67112014HCID 67112014, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
200 °C

Versuchsvorschrift

Add 4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (0.22 g, 1.11 mmol), 4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidine trihydrochloride (0.57 g, 1.2 eq), N-methylpyrrolidinone (10 mL) and diisopropylethylamine (1.16 mL, 6.0 eq) in a microwave tube. Seal the tube and heat in a microwave reactor at 200° C. for 30 minutes. Dilute the reaction mixture with water and extract with ethyl acetate. Wash with saturated aqueous sodium chloride. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by normal phase chromatography, eluting with a 1-10% methanol/dichloromethane gradient, to give 5-methyl-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one as a racemate (0.19 g, 36%). MS (ES) m/z=478 [M]+. Chiral separation (Chiralpak AD-H, 30% ethanol/70% CO2 w/0.2% isopropylamine) provides enantiomer 1 (>99% ee) and (R)-5-methyl-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one as enantiomer 2 (>99% ee). MS (ES) m/z=478 [M]+ for both compounds.

Aufarbeitung

  1. customSeal the tube
  2. extractionextract with ethyl acetate
  3. washWash with saturated aqueous sodium chloride
  4. dry with materialDry the organics over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by normal phase chromatography
  8. washeluting with a 1-10% methanol/dichloromethane gradient

Quellen und Nachweise

ORD-Eintrag
ord-4eac708f0aa34b63b7b0e9bf95028647
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436002B2

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