3-Acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid → 3-[(8-Amino-6-tetrazolo[1,5-b]pyridazinyl)-thiomethyl]-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid

HRID 1065848Notes

Reaction equation

HRID 1065848 reaction equation
C(O[CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH:17][C:18](=[O:48])[C:19]([C:23]3[N:24]=[C:25]([NH:28][C:29]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[S:26][CH:27]=3)=[N:20][O:21][CH3:22])[C:15](=[O:49])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=O)C.[NH2:50][C:51]1[C:52]2[N:53]([N:58]=[N:59][N:60]=2)[N:54]=[C:55]([SH:57])[CH:56]=1>C(#N)C>[NH2:50][C:51]1[C:52]2[N:53]([N:58]=[N:59][N:60]=2)[N:54]=[C:55]([S:57][CH2:5][C:6]2[CH2:7][S:8][C@@H:9]3[CH:16]([NH:17][C:18](=[O:48])[C:19]([C:23]4[N:24]=[C:25]([NH:28][C:29]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)[S:26][CH:27]=4)=[N:20][O:21][CH3:22])[C:15](=[O:49])[N:10]3[C:11]=2[C:12]([OH:14])=[O:13])[CH:56]=1

Participants

4

Reactant 2

HCID 1317115023-Acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acidHCID 178507975HCID 178507975, compound

Product 1

HCID 1317127243-[(8-Amino-6-tetrazolo[1,5-b]pyridazinyl)-thiomethyl]-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acidYield 80.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 3-acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (0.697 g; 0.001 mole) in anhydrous acetonitrile (50 ml), 8-amino-6-mercaptotetrazolo[1,5-b]pyridazine (0.336 g; 0.002 mole) was added and the resulting slurry was refluxed under a slow stream of nitrogen for 24 hours. Another portion of the mercapto compound (0.168 g; 0.001 mole) was added, and after further 16 hours of stirring at the reflux temperature, the mixture was cooled, the undissolved matter (unreacted mercapto compound) filtered off, the acetonitrile solution evaporated to dryness, the resulting foam taken up in warm methylene chloride (5 ml) and diethyl ether added (25 ml). The resulting white precipitate was collected by filtration and washed with a small amount of ethyl acetate and then with diethyl ether, thus giving 0.650 g of 3-[(8-amino-6-tetrazolo[1,5-b]pyridazinyl)-thiomethyl]-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn-isomer). This material was reacted with 50% aqueous formic acid, as described in Example 1, thus giving the title product, which was shown by T.L.C., I.R. and NMR to be identical to the product prepared in Example 1.

Workup

  1. temperaturethe resulting slurry was refluxed under a slow stream of nitrogen for 24 hours
  2. temperaturethe mixture was cooled
  3. filtrationthe undissolved matter (unreacted mercapto compound) filtered off
  4. customthe acetonitrile solution evaporated to dryness
  5. additiondiethyl ether added (25 ml)
  6. filtrationThe resulting white precipitate was collected by filtration
  7. washwashed with a small amount of ethyl acetate

Sources & evidence

ORD record
ord-2dddf0144d75475ab71af514d3244f3d
Source dataset
uspto-grants-1982_05
Patent number
US04331666

Reaction notes

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