1-(Methylsulfonyl)piperazine → 4-(4-Fluoro-2-methylindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1yl)propoxy)quinazoline

HRID 2068053Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2068053
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH3:17])[N:12]=[CH:11][N:10]=[C:9]2[O:18][C:19]1[C:20]([F:29])=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23]([CH3:28])=[CH:22]2.[CH3:30][S:31]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)(=[O:33])=[O:32]>CN(C=O)C>[F:29][C:20]1[C:19]([O:18][C:9]2[C:8]3[C:13](=[CH:14][C:15]([O:16][CH3:17])=[C:6]([O:5][CH2:4][CH2:3][CH2:2][N:37]4[CH2:38][CH2:39][N:34]([S:31]([CH3:30])(=[O:33])=[O:32])[CH2:35][CH2:36]4)[CH:7]=3)[N:12]=[CH:11][N:10]=2)=[CH:27][CH:26]=[C:25]2[C:21]=1[CH:22]=[C:23]([CH3:28])[NH:24]2

Komponenten

4

Edukt 2

HCID 7091611-(Methylsulfonyl)piperazineHCID 589602506-(3-Bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline

Produkt 1

HCID 670192434-(4-Fluoro-2-methylindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1yl)propoxy)quinazolineAusbeute 23 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of 6-(3-bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline (0.3 g, 0.652 mmol) and 1-(methylsulphonyl)piperazine (0.322 g, 1.95 mmol), (prepared as described for the starting material in Example 2), in DMF (4 ml) was stirred at 80° C. for 2.5 hours. The volatiles were removed under vacuum and the residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The residue was triturated under diethyl ether and the resulting solid was filtered, washed with diethyl ether and dried under vacuum to give 4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline (0.08 g, 23%).

Aufarbeitung

  1. customThe volatiles were removed under vacuum
  2. customthe residue was purified by column chromatography
  3. washeluting
  4. temperaturewith increasingly polar mixtures of methylene chloride and methanol
  5. additionThe fractions containing the expected product
  6. customevaporated
  7. customThe residue was triturated under diethyl ether
  8. filtrationthe resulting solid was filtered
  9. washwashed with diethyl ether
  10. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-8ac6bb7d8ca44efab1404f0c1094e2b3
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08293902B2

Notizen zur Reaktion

Wird geladen…