N,N-Dimethylaniline → 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-formylamino-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid

HRID 325397Notes

Reaction equation

HRID 325397 reaction equation
[CH3:1][N:2]1[C:6]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[CH:19]([NH2:20])[C:18](=[O:21])[N:13]3[C:14]=2[C:15]([OH:17])=[O:16])=[N:5][N:4]=[N:3]1.CN(C)C1C=CC=CC=1.C[Si](Cl)(C)C.[CH:36]([NH:38][C:39]1[S:40][CH:41]=[C:42]([C:44](=[O:48])[C:45](O)=[O:46])[N:43]=1)=[O:37].S(Cl)(Cl)=O>C(Cl)Cl.O.CN(C)C=O.C(N(CC)CC)C>[CH3:1][N:2]1[C:6]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[CH:19]([NH:20][C:45](=[O:46])[C:44]([C:42]4[N:43]=[C:39]([NH:38][CH:36]=[O:37])[S:40][CH:41]=4)=[O:48])[C:18](=[O:21])[N:13]3[C:14]=2[C:15]([OH:17])=[O:16])=[N:5][N:4]=[N:3]1

Participants

11

Reactant 6

HCID 949N,N-DimethylanilineHCID 6397ChlorotrimethylsilaneHCID 24386Thionyl ChlorideHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 13116693(2-Formamido-1,3-thiazol-4-yl)(oxo)acetic acidHCID 178522624HCID 178522624, compound

Product 1

HCID 1317125693-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-formylamino-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent

Procedure

A suspension of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (1.46 g.), triethylamine (0.9292 g.) and dimethylaniline (0.713 g.) in methylene chloride (30 ml.) was stirred for 20 minutes at room temperature. To the mixture was added a solution of trimethylsilyl chloride (1.043 g.) in methylene chloride (10 ml.) over 5 minutes under ice-cooling, and the mixture was stirred for 2 hours at room temperature and then cooled to -25° C. On the other hand, a suspension of 2-(2-formylamino-1,3-thiazol-4-yl)glyoxylic acid, which can be represented as 2-(2-formylimino-2,3-dihydro-1,3-thiazol-4-yl)glyoxylic acid, (0.96 g.), thionyl chloride (0.697 g.) and dimethylformamide (0.214 g.) in methylene chloride (12 ml.) was stirred for 4 hours, and the mixture was added to the above obtained cooled mixture over 12 minutes at -25° to -20° C. The mixture was further stirred for 30 minutes at the same temperature and for 30 minutes at -20° to -10° C. After the reaction, the reaction mixture was added to water (100 ml.), and stirred for 30 minutes at room temperature. The white precipitates were collected by filtration and then dried to give dark brown powder of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-formylamino-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-formylimino-2,3-dihydro-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 2 hours at room temperature
  3. temperaturecooled to -25° C
  4. stirringwas stirred for 4 hours
  5. additionthe mixture was added to the
  6. customabove obtained
  7. temperaturecooled mixture over 12 minutes at -25° to -20° C
  8. stirringThe mixture was further stirred for 30 minutes at the same temperature and for 30 minutes at -20° to -10° C
  9. customAfter the reaction
  10. stirringstirred for 30 minutes at room temperature
  11. customThe white precipitates
  12. filtrationwere collected by filtration
  13. customdried

Sources & evidence

ORD record
ord-bdaffd053cf0473ab748797322d2aa81
Source dataset
uspto-grants-1984_04
Patent number
US04440766

Reaction notes

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