Hydrochloric Acid → 7-[2-(2-Aminothiazol-4-yl)-2-(3-aminopropoxyimino)acetamido]-3-(5-aminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 1154124Notes

Reaction equation

HRID 1154124 reaction equation
C([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:41][O:42][CH2:43][CH2:44][CH2:45][NH:46]C(OC(C)(C)C)=O)[C:10]([NH:12][CH:13]2[C:39](=[O:40])[N:15]3[C:16]([C:36]([OH:38])=[O:37])=[C:17]([CH2:20][S:21][C:22]4[S:23][C:24]([CH2:27][NH:28]C(OC(C)(C)C)=O)=[N:25][N:26]=4)[CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1)=O.Cl.CO>O1CCCC1>[NH2:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:41][O:42][CH2:43][CH2:44][CH2:45][NH2:46])[C:10]([NH:12][CH:13]2[C:39](=[O:40])[N:15]3[C:16]([C:36]([OH:38])=[O:37])=[C:17]([CH2:20][S:21][C:22]4[S:23][C:24]([CH2:27][NH2:28])=[N:25][N:26]=4)[CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 1317129167-[2-(2-Formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetamido]-3-(5-tert-butoxycarbonylaminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317129177-[2-(2-Aminothiazol-4-yl)-2-(3-aminopropoxyimino)acetamido]-3-(5-aminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acidYield 55.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 7-[2-(2-formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetamido]-3-(5-tert-butoxycarbonylaminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 1.5 g.), conc. hydrochloric acid (0.8 ml.), methanol (30 ml.) and tetrahydrofuran (30 ml.) was stirred at room temperature for 3 hours. After evaporation, methanol was added to the residue. The solution was evaporated in vacuo again, and the residue was dissolved in water (30 ml.). The solution was adjusted to pH 3.5 with saturated aqueous sodium bicarbonate solution under ice-cooling. The solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" (trademark: Mitsubishi Chemical Industries Ltd.) and eluted with 30% aqueous isopropyl alcohol. The eluate was concentrated in vacuo and lyophilized to give 7-[2-(2-aminothiazol-4-yl)-2-(3-aminopropoxyimino)acetamido]-3-(5-aminomethyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 0.6 g.).

Workup

  1. customAfter evaporation, methanol
  2. additionwas added to the residue
  3. customThe solution was evaporated in vacuo again
  4. dissolutionthe residue was dissolved in water (30 ml.)
  5. temperaturecooling
  6. wash" (trademark: Mitsubishi Chemical Industries Ltd.) and eluted with 30% aqueous isopropyl alcohol
  7. concentrationThe eluate was concentrated in vacuo

Sources & evidence

ORD record
ord-50c3696f63d74cbfa3d98b1b7c4be321
Source dataset
uspto-grants-1984_12
Patent number
US04487767

Reaction notes

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