N,N-Dimethylbenzylamine → 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

HRID 1659412Notes

Reaction equation

HRID 1659412 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH:8]([C:12]1[N:13]=[C:14]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[S:15][CH:16]=1)[C:9]([OH:11])=O.CN(CC1C=CC=CC=1)C.ClC(OCCCC)=O.[CH3:40][N:41]1[C:45]([S:46][CH2:47][C:48]2[CH2:49][S:50][C@@H:51]3[CH:58]([NH2:59])[C:57](=[O:60])[N:52]3[C:53]=2[C:54]([OH:56])=[O:55])=[N:44][N:43]=[N:42]1>O1CCCC1.C(N(CC)CC)C>[CH3:40][N:41]1[C:45]([S:46][CH2:47][C:48]2[CH2:49][S:50][C@@H:51]3[CH:58]([NH:59][C:9](=[O:11])[CH:8]([O:7][CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)[C:12]4[N:13]=[C:14]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[S:15][CH:16]=4)[C:57](=[O:60])[N:52]3[C:53]=2[C:54]([OH:56])=[O:55])=[N:44][N:43]=[N:42]1

Participants

8

Reactant 5

HCID 7681N,N-DimethylbenzylamineHCID 61140Butyl chloroformateHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 202543832-(2-Tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetic acidHCID 178505078HCID 178505078, compound

Product 1

HCID 1317125683-(1-methyl-1H-tetrazol-5-yl)thiomethyl7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8471TriethylamineSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of 2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetic acid, which can be represented as 2-(2-tetrahydropyranyl)oxy-2-(2-mesylimino-2,3-dihydro-1,3-thiazol-4-yl)acetic acid, (350 mg.), triethylamine (96 mg.), N,N,-dimethylbenzylamine (half drop) and tetrahydrofuran (7 ml.) was dropwise added a mixture of butyl chloroformate (130 mg.) and tetrahydrofuran (1 ml.) over 1 minute at -15° C., and then the mixture was stirred for 30 minutes at -15° to -10° C. To the mixture was added all at once a mixture of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (224 mg.), triethylamine (80 mg.) and 50% tetrahydrofuran aqueous solution (10 ml.) which was cooled at 0° C., and the mixture was stirred for 30 minutes under ice-cooling and further stirred for 2 hours at room temperature. After the reaction, the reaction mixture was concentrated. The residue was adjusted to pH 8 with 5% sodium bicarbonate aqueous solution and washed with ethyl acetate. Thus obtained aqueous layer was adjusted to pH 1 with 10% hydrochloric acid and extracted with ethyl acetate. After distillation of the solvent from the extract, the residue was pulverized in diethyl ether, collected by filtration and dried to give pale brown powder of 3-(1-methyl1H-tetrazol-5-yl)thiomethyl-7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylimino-2,3-dihydro1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, (270 mg.).

Workup

  1. additionwas dropwise added
  2. additionTo the mixture was added all at once
  3. stirringthe mixture was stirred for 30 minutes under ice-
  4. temperaturecooling
  5. stirringfurther stirred for 2 hours at room temperature
  6. customAfter the reaction
  7. concentrationthe reaction mixture was concentrated
  8. washwashed with ethyl acetate
  9. extractionextracted with ethyl acetate
  10. distillationAfter distillation of the solvent from the extract
  11. filtrationcollected by filtration
  12. customdried

Sources & evidence

ORD record
ord-ac7e89ad24fb47c39e42c6408d939b87
Source dataset
uspto-grants-1981_12
Patent number
US04303655

Reaction notes

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