Dimethylformamide → 4-[4-((R)-2-hydroxy-4-methyl-pentanoyl)-piperazin-1-yl]-2-(2-hydroxy-phenyl)-quinazoline-6-carbonitrile

HRID 2079298Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2079298
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[OH:18])[N:6]=[C:5]2[N:19]1[CH2:24][CH2:23][N:22]([C:25](=[O:32])[C@H:26]([OH:31])[CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:21][CH2:20]1.CCOC(C)=O.[CH3:39][N:40](C=O)C>[C-]#N.[C-]#N.[Zn+2]>[OH:31][C@H:26]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:25]([N:22]1[CH2:21][CH2:20][N:19]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:39]#[N:40])[CH:3]=3)[N:8]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])[N:6]=2)[CH2:24][CH2:23]1)=[O:32]

Komponenten

5

Edukt 3

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 136121577(R)-1-(4-(6-bromo-2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one

Produkt 1

HCID 1361215804-[4-((R)-2-hydroxy-4-methyl-pentanoyl)-piperazin-1-yl]-2-(2-hydroxy-phenyl)-quinazoline-6-carbonitrileAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 11186Zinc cyanide (Zn(CN)2)Katalysator

Reaktionsbedingungen

Temperatur
200 °C

Versuchsvorschrift

(R)-1-(4-(6-Bromo-2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one (188 mg, 0.38 mmol), Zn(CN)2 (44 mg, 0.38 mmol), and Pd(Ph3)4 (6.5 mg, 0.0112 mmol) were dissolved in DMF (4 mL) and the reaction mixture was heated in a microwave synthesizer at 200° C. for 15 minutes. EtOAc (50 mL) was added and the mixture was washed twice with H2O. The organic layer was dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-40% EtOAc in CH2Cl2:hexanes (1:1) gave 4-[4-((R)-2-hydroxy-4-methyl-pentanoyl)-piperazin-1-yl]-2-(2-hydroxy-phenyl)-quinazoline-6-carbonitrile (127 mg, 75%). LC/MS: m/z 446 (M+H)+ at 3.24 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J=1.5 Hz, 1H), 8.46 (dd, J=8.4, 1.8 Hz, 1H), 8.15 (dd, J=8.7, 1.7 Hz, 1H), 8.00 (d, J=8.7 Hz, 1H), 7.45-7.41 (m, 1H), 6.99-6.95 (m, 2H), 4.94 (d, J=7.0 Hz, 1H), 4.39-4.36 (m, 1H), 4.14-4.04 (m, 4H), 3.89-3.67 (m, 4H), 1.82-1.76 (m, 1H), 1.47-1.37 (m, 2H), 0.93-0.91 (m, 6H) ppm.

Aufarbeitung

  1. washthe mixture was washed twice with H2O
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-fd321e33b4ab4bd9b32f0f718d524260
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07928107B2

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