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

HRID 1106181

Reaktionsgleichung

Reaktionsgleichung von HRID 1106181
[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 m mol) 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and 175 ml of dichloromethane, 10.2 ml (75 m mol) triethylamine and 9.5 ml (75 m mol) chlorotrimethylsilane are added and the reaction mixture stirred at room temperature for 1 hour. To a solution of 7.86 g (50 m mol) of N-Acetyl-L-proline in 100 ml of dichloromethane at -10° C., 5.5 ml (50 m mol) of N-methylmorpholine and 6.5 ml (50 m mol) of isobutyl chloroformate are added and stirred at -10° C. for 1/2 hour. To this cold mixed anhydride mixture is added the silylated 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and the resulting mixture is stirred for 3 hrs in an ice bath and overnight at room temperature. Next, 25 ml of isopropanol is added to the reaction mixture and stirred. The reaction mixture is evaporated and the residue is triturated with ice and water. The solid is 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, m.p. 288°-290° dec. From the filtrate an additional 3.94 g of product is obtained.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-a32169fd10f041cba76822b2e56e71c9
Quelldatensatz
uspto-grants-1982_01
Patentnummer
US04311698

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