N,N-Dimethylaniline → 7beta-[2-(5-Tert.-butoxycarbonylaminomethyl-2-thienyl)-acetylamino]-3-[(6-methyl-1-oxido-pyridazin-3-yl-thio)-methyl]-ceph-3-em-4-carboxylic acid

HRID 2398514

Reaktionsgleichung

Reaktionsgleichung von HRID 2398514
CN(C)C1C=CC=CC=1.C[Si](C)(C)Cl.[NH2:15][C@@H:16]1[C:36](=[O:37])[N:18]2[C:19]([C:33]([OH:35])=[O:34])=[C:20]([CH2:23][S:24][C:25]3[N:26]=[N+:27]([O-:32])[C:28]([CH3:31])=[CH:29][CH:30]=3)[CH2:21][S:22][C@H:17]12.[C:38]([O:42][C:43]([NH:45][CH2:46][C:47]1[S:51][C:50]([CH2:52][C:53](O)=[O:54])=[CH:49][CH:48]=1)=[O:44])([CH3:41])([CH3:40])[CH3:39].C(Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C)C=O.C(N(CC)CC)C>[C:38]([O:42][C:43]([NH:45][CH2:46][C:47]1[S:51][C:50]([CH2:52][C:53]([NH:15][C@@H:16]2[C:36](=[O:37])[N:18]3[C:19]([C:33]([OH:35])=[O:34])=[C:20]([CH2:23][S:24][C:25]4[N:26]=[N+:27]([O-:32])[C:28]([CH3:31])=[CH:29][CH:30]=4)[CH2:21][S:22][C@H:17]23)=[O:54])=[CH:49][CH:48]=1)=[O:44])([CH3:41])([CH3:40])[CH3:39]

Komponenten

9

Edukt 5

HCID 949N,N-DimethylanilineHCID 6397ChlorotrimethylsilaneHCID 65578Oxalyl chlorideHCID 202932812-[5-({[(Tert-butoxy)carbonyl]amino}methyl)thiophen-2-yl]aceticacidHCID 706356077beta-Amino-3-[(6-methyl-1-oxido-pyridazin-3-ylthio)-methyl]-ceph-3-em-4-carboxylic acid

Produkt 1

HCID 706354887beta-[2-(5-Tert.-butoxycarbonylaminomethyl-2-thienyl)-acetylamino]-3-[(6-methyl-1-oxido-pyridazin-3-yl-thio)-methyl]-ceph-3-em-4-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

1.50 ml of triethylamine, 1.6 ml of N,N-dimethylaniline and 2,3 ml of trimethylchlorosilane are added to a stirred suspension of 2.13 g of 7β-amino-3-[(6-methyl-1-oxido-pyridazin-3-ylthio)-methyl]-ceph-3-em-4-carboxylic acid in 20 ml of methylene chloride at 20°-25° C. The mixture is warmed to 40° C over the course of 20 minutes, whilst stirring, and is then cooled to +5° C. At the same time, 1.95 g of 2-(5-tert.-butoxycarbonylaminomethyl-2-thienyl)-acetic acid are dissolved in 20 ml of methylene chloride, 0.05 ml of dimethylformamide and 5 ml of oxalyl chloride. The mixture is stirred for 30 minutes at the reflux temperature under a slight stream of nitrogen, the readily volatile constituents are distilled off in vacuo and the oily residue is dissolved in 10 ml of methylene chloride. This solution is added, at 5°-10° C, to the solution which contains the amine component which has now been silylated. This mixture is stirred for 2 hours at 10°-25° C and poured into water, the pH is adjusted to approx. 7 with sodium bicarbonate, the whole is extracted with methylene chloride and carefully acidified to approx. pH 2 with concentrated hydrochloric acid, and the precipitate formed is filtered off. It is repeatedly washed with water and after subsequent drying of the filter residue in a high vacuum over potassium hydroxide, 7β-[2-(5-tert.-butoxycarbonylaminomethyl-2-thienyl)-acetylamino]-3-[(6-methyl-1-oxido-pyridazin-3-yl-thio)-methyl]-ceph-3-em-4-carboxylic acid is obtained; thin layer chromatogram (silica gel; glacial acetic acid/water/butanol, 45:10:45): Rf = 0.58; infrared absorption spectrum (in mineral oil): bands at 5.63μ and 5.96μ.

Aufarbeitung

  1. temperatureis then cooled to +5° C
  2. stirringThe mixture is stirred for 30 minutes at the reflux temperature under a slight stream of nitrogen
  3. distillationthe readily volatile constituents are distilled off in vacuo
  4. dissolutionthe oily residue is dissolved in 10 ml of methylene chloride
  5. additionThis solution is added, at 5°-10° C, to the solution which
  6. stirringThis mixture is stirred for 2 hours at 10°-25° C
  7. additionpoured into water
  8. extractionthe whole is extracted with methylene chloride
  9. customthe precipitate formed
  10. filtrationis filtered off
  11. washIt is repeatedly washed with water
  12. dry with materialafter subsequent drying of the filter residue in a high vacuum over potassium hydroxide

Quellen und Nachweise

ORD-Eintrag
ord-c753836f20aa473f98c266f9d5c4d043
Quelldatensatz
uspto-grants-1977_05
Patentnummer
US04024249

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