Alkylation of isonipecotamide (I) with n-butyl bromide in the presence of potassium carbonate gives the amide (II), which is reduced with lithium aluminum hydride to afford 1-butyl-4-piperidinylmethylamine (III). Conversion of indole-3-carboxylic acid (IV) to the acid chloride (V) is carried out with oxalyl chloride in dichloromethane containing N,N-dimethylformamide (DMF). Coupling of the amine (III) with the acid chloride (V) in dichloromethane in the presence of triethylamine gives N-[(1-butyl-4-piperidinyl)methyl]indole-3-carboxamide (VI). N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]-oxazino[3,2-a] indole-10-carboxamide (VIII) is formed by treatment of the amide (VI) with N-chlorosuccinimide in chloroform followed by reaction with 3-bromopropanol and cyclization of the intermediate ether (VII) with potassium carbonate in acetone. Conversion to N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a] indole-10-carboxamide hydrochloride (SB-207266) is effected by treatment of (VIII) with anhydrous HCl in ethanol.

Alkylation of isonipecotamide (I) with n-butyl bromide in the presence of potassium carbonate gives the amide (II), which is reduced with lithium aluminum hydride to afford 1-butyl-4-piperidinylmethylamine (III). Conversion of indole-3-carboxylic acid (IV) to the acid chloride (V) is carried out with oxalyl chloride in dichloromethane containing N,N-dimethylformamide (DMF). Coupling of the amine (III) with the acid chloride (V) in dichloromethane in the presence of triethylamine gives N-[(1-butyl-4-piperidinyl)methyl]indole-3-carboxamide (VI). N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]-oxazino[3,2-a] indole-10-carboxamide (VIII) is formed by treatment of the amide (VI) with N-chlorosuccinimide in chloroform followed by reaction with 3-bromopropanol and cyclization of the intermediate ether (VII) with potassium carbonate in acetone. Conversion to N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a] indole-10-carboxamide hydrochloride (SB-207266) is effected by treatment of (VIII) with anhydrous HCl in ethanol.

Alkylation of isonipecotamide (I) with n-butyl bromide in the presence of potassium carbonate gives the amide (II), which is reduced with lithium aluminum hydride to afford 1-butyl-4-piperidinylmethylamine (III). Conversion of indole-3-carboxylic acid (IV) to the acid chloride (V) is carried out with oxalyl chloride in dichloromethane containing N,N-dimethylformamide (DMF). Coupling of the amine (III) with the acid chloride (V) in dichloromethane in the presence of triethylamine gives N-[(1-butyl-4-piperidinyl)methyl]indole-3-carboxamide (VI). N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]-oxazino[3,2-a] indole-10-carboxamide (VIII) is formed by treatment of the amide (VI) with N-chlorosuccinimide in chloroform followed by reaction with 3-bromopropanol and cyclization of the intermediate ether (VII) with potassium carbonate in acetone. Conversion to N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a] indole-10-carboxamide hydrochloride (SB-207266) is effected by treatment of (VIII) with anhydrous HCl in ethanol.