Allyl Alcohol → 3-[(Allyloxy)methyl]-N-(4-chlorobenzyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide

HRID 23638

Reaktionsgleichung

Reaktionsgleichung von HRID 23638
[CH2:1]([OH:4])[CH:2]=[CH2:3].C([Li])CCC.Br[CH2:11][C:12]1[C:16]2[N:17]([CH3:27])[CH:18]=[C:19]([C:22]([O:24]CC)=O)[C:20](=[O:21])[C:15]=2[S:14][CH:13]=1.[Cl:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33][NH2:34])=[CH:31][CH:30]=1>C1COCC1.CN(C=O)C.CCOCC>[CH2:1]([O:4][CH2:11][C:12]1[C:16]2[N:17]([CH3:27])[CH:18]=[C:19]([C:22]([NH:34][CH2:33][C:32]3[CH:35]=[CH:36][C:29]([Cl:28])=[CH:30][CH:31]=3)=[O:24])[C:20](=[O:21])[C:15]=2[S:14][CH:13]=1)[CH:2]=[CH2:3]

Komponenten

8

Edukt 4

HCID 7858Allyl AlcoholHCID 660364-ChlorobenzylamineHCID 22574331Ethyl 3-(bromomethyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 225743553-[(Allyloxy)methyl]-N-(4-chlorobenzyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a cold (0° C.), stirred solution of 0.82 mL of allyl alcohol in 12 mL of dry THF, under argon, is added 2.1 mL of a 2.5 M solution of butyllithium in hexanes. The solution is stirred for 5 min, then added via cannula to a cold (0° C.), stirred mixture of 1.25 g of ethyl 3-(bromomethyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxylate (Preparation 19) in 8 mL of dry DMF. The resulting solution is stirred at 0° C. for 20 min, then quenched with dil. HCl. Aqueous workup (EtOAc/dil HCl) followed by flash chromatography on silica using 3% MeOH in CH2Cl2 affords a mixture of ethyl and allyl esters (873 mg). A mixture of 165 mg of the mixed esters and 580 mg of p-chlorobenzylamine is heated at 120° C. for 18 h, then cooled and diluted with ether. The resulting solid is filtered, washed well with ether, and dried in vacuo. Flash chromatography of the solid on silica using 2% MeOH in CH2Cl2 provides 922 mg of the title compound as a pale yellow solid. Recrystallization from EtOAc affords glistening yellow prisms.

Aufarbeitung

  1. additionadded via cannula to a cold (0° C.)
  2. stirringstirred
  3. stirringThe resulting solution is stirred at 0° C. for 20 min
  4. customquenched with dil. HCl
  5. customaffords
  6. temperaturecooled
  7. filtrationThe resulting solid is filtered
  8. washwashed well with ether
  9. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-bfdc5338683a418fa35090f67c40fe78
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06852731B2

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