Chlorotrimethylsilane → 6-[4-(N-acetyl-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid

HRID 1277797

Reaktionsgleichung

Reaktionsgleichung von HRID 1277797
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10](=[O:17])[C:11](=[CH:15][CH:16]=2)[C:12]([OH:14])=[O:13])=[CH:4][CH:3]=1.Cl[Si](C)(C)C.[C:23]([N:26]1[CH2:33][CH2:32][CH2:31][C@H:27]1[C:28](O)=[O:29])(=[O:25])[CH3:24].CN1CCOCC1.ClC(OCC(C)C)=O>ClCCl.C(O)(C)C.C(N(CC)CC)C>[C:23]([N:26]1[CH2:33][CH2:32][CH2:31][C@H:27]1[C:28]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:9][C:10](=[O:17])[C:11](=[CH:15][CH:16]=2)[C:12]([OH:14])=[O:13])=[CH:6][CH:7]=1)=[O:29])(=[O:25])[CH3:24]

Komponenten

9

Edukt 5

HCID 6397ChlorotrimethylsilaneHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 66141N-Acetyl-L-prolineHCID 129189566-(4-Aminophenyl)-1,2-dihydro-2-oxonicotinic acid

Produkt 1

HCID 129189646-[4-(N-acetyl-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acidAusbeute 52,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3776IsopropanolLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a suspension of 5.75 g (25 mM) 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and 175 ml of dichloromethane, 10.5 ml (75 mM) triethylamine and 9.5 ml (75 mM) chlorotrimethylsilane were added and stirred at room temperature for 1 hour. To a solution of 7.86 g (50 mM) of N-Acetyl-L-proline in 100 ml of dichloromethane at -10° C., 5.5 ml (50 mM) of N-methylmorpholine and 6.5 ml (50 mM) of isobutyl chloroformate were added and stirred at -10° C. for 1/2 hour. To this cold mixed anhydride mixture was added the silylated 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and the resulting mixture was stirred for 3 hrs in an ice bath and overnight at room temperature. Next, 25 ml of isopropanol was added to the reaction mixture and stirred. The reaction mixture was evaporated and the residue was triturated with ice and water. The solid was collected by filtration and washed with water, isopropanol and ether to yield 4.82 g of 6-[4-(N-acetyl-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid, mp 288°-290° dec. From the filtrate an additional 3.94 g of product was obtained.

Aufarbeitung

  1. additionwere added
  2. stirringstirred at -10° C. for 1/2 hour
  3. stirringthe resulting mixture was stirred for 3 hrs in an ice bath and overnight at room temperature
  4. stirringstirred
  5. customThe reaction mixture was evaporated
  6. customthe residue was triturated with ice and water
  7. filtrationThe solid was collected by filtration
  8. washwashed with water, isopropanol and ether

Quellen und Nachweise

ORD-Eintrag
ord-7491cc8d5c81416faee3f90a185068ca
Quelldatensatz
uspto-grants-1981_07
Patentnummer
US04278681

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