Sodium Iodide → Benzhydryl 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-(1,2,4-triazolo[4,3-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylate

HRID 615417Notes

Reaction equation

HRID 615417 reaction equation
[SH:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[N:9][N:10]=2)[N:7]=1.[C:11]([O:15][C:16]([CH2:18][O:19][N:20]=[C:21]([C:52]1[N:53]=[CH:54][S:55][CH:56]=1)[C:22]([NH:24][CH:25]1[C:50](=[O:51])[N:27]2[C:28]([C:34]([O:36][CH:37]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[O:35])=[C:29]([CH2:32]Cl)[CH2:30][S:31][C@H:26]12)=[O:23])=[O:17])([CH3:14])([CH3:13])[CH3:12].[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.O.C(OCC)(=O)C>[C:11]([O:15][C:16]([CH2:18][O:19][N:20]=[C:21]([C:52]1[N:53]=[CH:54][S:55][CH:56]=1)[C:22]([NH:24][CH:25]1[C:50](=[O:51])[N:27]2[C:28]([C:34]([O:36][CH:37]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)=[O:35])=[C:29]([CH2:32][S:1][C:2]3[CH:3]=[CH:4][C:5]4[N:6]([CH:8]=[N:9][N:10]=4)[N:7]=3)[CH2:30][S:31][C@H:26]12)=[O:23])=[O:17])([CH3:12])([CH3:13])[CH3:14]

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 131714103Benzhydryl 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-chloromethyl-3-cephem-4-carboxylateHCID 178527714HCID 178527714, compound

Product 1

HCID 131714105Benzhydryl 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-(1,2,4-triazolo[4,3-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylateYield 20.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Mercapto-1,2,4-triazolo[4,3-b]pyridazine (4.7 g) was added to a stirred suspension of benzhydryl 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (5.0 g) and sodium iodide (4.6 g) in N,N-dimethylformamide (35 ml) and the mixture was stirred for 2 hours at ambient temperature. To the reaction mixture was added a mixture of ethyl acetate and water and then the resultant mixture was adjusted to pH 7.5 with 20% aqueous solution of sodium carbonate. The separated organic layer was washed with saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The crude product obtained by concentration of organic layer was purified by silica gel column chromatography using ethyl acetate as an eluate. The fractions containing the object compound were evaporated to give benzhydryl 7-[2-t-butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetamido]-3-(1,2,4-triazolo[4,3-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylate (syn isomer) (1.2 g).

Workup

  1. additionTo the reaction mixture was added
  2. washThe separated organic layer was washed with saturated aqueous solution of sodium chloride
  3. dry with materialdried over magnesium sulfate
  4. customThe crude product obtained by concentration of organic layer
  5. customwas purified by silica gel column chromatography
  6. additionThe fractions containing the object compound
  7. customwere evaporated

Sources & evidence

ORD record
ord-8c74f6fd07d842d7bb1bc4fd2964da77
Source dataset
uspto-grants-1985_02
Patent number
US04499088

Reaction notes

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