Conversion of alcohol (I) into chloro derivative (II) by reaction with PCl3 in DMF, followed by reaction with PCl5/pyridine in CH2Cl2, treatment with iBuOH and acidic treatment with TsOH, provides 7-amino-3-chlorocephalosporanic acid diphenylmethyl ester toluene sulfonic acid salt (III). Separately, O-protection of thiazole derivative (IV) by reaction with TrtCl and tert-BuOK in THF affords trityl protected compound (V), whose ethyl carboxylate group is hydrolyzed by means of KOH in EtOH to furnish carboxylic acid (VI). Chlorination of the thiazol ring of (VI) by means of N-chlorosuccinimide (NCS) in DMF yields chlorothiazole derivative (VII), which is then condensed with 7-amino-3-chlorocephalosporanic acid derivative (III) by means of POCl3 in THF to give acetamido derivative (VIII). Separately, the synthesis of pyridine derivative (XIV) is performed by following these steps: alkylation of chloropyridine (IX) by means of LDA and ethyl formate provides derivative (X), which is then reduced by means of NaBH4 to furnish alcohol (XI). Finally, (XIV) is obtained by first chlorination of (XI) with SOCl2 in DMF to afford chloromethyl derivative (XII), and subsequent condensation of (XII) with N-Boc-ethanethiol (XIII) either by means of Et3N in CH2Cl2 or by means of NaI and DIEA in DMF. Treatment of derivative (VIII) with NaSH in DMF, followed by coupling with chloropyridine derivative (XIV) in DMF, furnishes compound (XV), which is finally converted into the desired product by protecting groups removal with TFA/anisole or TFA/triethylsilane in CH2Cl2, and treatment with MsOH in H2O.

Conversion of alcohol (I) into chloro derivative (II) by reaction with PCl3 in DMF, followed by reaction with PCl5/pyridine in CH2Cl2, treatment with iBuOH and acidic treatment with TsOH, provides 7-amino-3-chlorocephalosporanic acid diphenylmethyl ester toluene sulfonic acid salt (III). Separately, O-protection of thiazole derivative (IV) by reaction with TrtCl and tert-BuOK in THF affords trityl protected compound (V), whose ethyl carboxylate group is hydrolyzed by means of KOH in EtOH to furnish carboxylic acid (VI). Chlorination of the thiazol ring of (VI) by means of N-chlorosuccinimide (NCS) in DMF yields chlorothiazole derivative (VII), which is then condensed with 7-amino-3-chlorocephalosporanic acid derivative (III) by means of POCl3 in THF to give acetamido derivative (VIII). Separately, the synthesis of pyridine derivative (XIV) is performed by following these steps: alkylation of chloropyridine (IX) by means of LDA and ethyl formate provides derivative (X), which is then reduced by means of NaBH4 to furnish alcohol (XI). Finally, (XIV) is obtained by first chlorination of (XI) with SOCl2 in DMF to afford chloromethyl derivative (XII), and subsequent condensation of (XII) with N-Boc-ethanethiol (XIII) either by means of Et3N in CH2Cl2 or by means of NaI and DIEA in DMF. Treatment of derivative (VIII) with NaSH in DMF, followed by coupling with chloropyridine derivative (XIV) in DMF, furnishes compound (XV), which is finally converted into the desired product by protecting groups removal with TFA/anisole or TFA/triethylsilane in CH2Cl2, and treatment with MsOH in H2O.

Alternatively, derivative (XV) can be obtained from the corresponding mesylate derivative: Treatment of alcohol (I) with MsCl and Et3N in CH2Cl2 yields methansulfonyl derivative (XVI), which is then converted into mesylated aminochlorocephalosporanic acid derivative (XVII) by following these steps: First treatment with metachloroperbenzoic acid (MCPBA) in dichloromethane, followed by reaction with KI and Tf2O in acetonitrile, chlorination with PCl5 and pyridine in dichloromethane, treatment with iBuOH and acidic treatment with TosOH. Condensation of derivative (XVII) with 7-chlorothiazole derivative (VII) by means of (PhO)2POCl in THF provides acetamido derivative (XVIII), which is then treated with chloropyridine derivative (XIV) and NaSH in DMF in DMF to afford compound (XV).

Conversion of alcohol (I) into chloro derivative (II) by reaction with PCl3 in DMF, followed by reaction with PCl5/pyridine in CH2Cl2, treatment with iBuOH and acidic treatment with TsOH, provides 7-amino-3-chlorocephalosporanic acid diphenylmethyl ester toluene sulfonic acid salt (III). Separately, O-protection of thiazole derivative (IV) by reaction with TrtCl and tert-BuOK in THF affords trityl protected compound (V), whose ethyl carboxylate group is hydrolyzed by means of KOH in EtOH to furnish carboxylic acid (VI). Chlorination of the thiazol ring of (VI) by means of N-chlorosuccinimide (NCS) in DMF yields chlorothiazole derivative (VII), which is then condensed with 7-amino-3-chlorocephalosporanic acid derivative (III) by means of POCl3 in THF to give acetamido derivative (VIII). Separately, the synthesis of pyridine derivative (XIV) is performed by following these steps: alkylation of chloropyridine (IX) by means of LDA and ethyl formate provides derivative (X), which is then reduced by means of NaBH4 to furnish alcohol (XI). Finally, (XIV) is obtained by first chlorination of (XI) with SOCl2 in DMF to afford chloromethyl derivative (XII), and subsequent condensation of (XII) with N-Boc-ethanethiol (XIII) either by means of Et3N in CH2Cl2 or by means of NaI and DIEA in DMF. Treatment of derivative (VIII) with NaSH in DMF, followed by coupling with chloropyridine derivative (XIV) in DMF, furnishes compound (XV), which is finally converted into the desired product by protecting groups removal with TFA/anisole or TFA/triethylsilane in CH2Cl2, and treatment with MsOH in H2O.