STX-213

合成路线:1) 4-Chloro-2'-bromoacetophenone (I) is condensed with 2-amino 5-chloropyridine (II) to give 6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine (III).2) The above compound is reacted with formaldehyde and dimethylamine under Mannich conditions affording the 3-dimethylaminomethyl derivative (IV),which is subsequently quaternized with methyl iodide to afford the quaternary iodide (V).3) Displacement of trimethylamine from salt (V) with cyanide ion leads to formation of the nitrile (VI),which on hydrolysis with hydrochloric acid in acetic acid gives the corresponding acid (VII).4) In situ conversion of the acid to its acid chloride with phosphorus oxychloride followed by treatment with di-n-propylamine then leads to alpidem.

合成路线:The oxidation of 3-(benzyloxy)estrone (I) with I2 and KOH in refluxing methanol gives 3-(benzyloxy)-16,17-seco-estra-1,3,5(10)-triene-16,17-dioic acid (II),which is cyclized with urea at 180篊 to yield the cyclic imide (III).The alkylation of (III) with propyl chloride (IV) and NaH in DMF affords the N-propyl derivative (V).Alternatively,the N-propyl derivative (V) can also be obtained by direct cyclization of diacid (II) with propylamine (VI) at 180?C.The debenzylation of (V) to the 3-hydroxy derivative (VII) is performed by hydrogenation with H2 over Pd/C in methanol/THF.Finally,compound (VII) is treated with chlorosulfonamide and NaH in DMF to provide the target sulfamate.

合成路线:The oxidation of 3-(benzyloxy)estrone (I) with I2 and KOH in refluxing methanol gives 3-(benzyloxy)-16,17-seco-estra-1,3,5(10)-triene-16,17-dioic acid (II),which is cyclized with urea at 180?C to yield the cyclic imide (III).The alkylation of (III) with 3-(chloromethyl)pyridine (IV) and NaH in DMF affords the N-(3-pyridylmethyl) derivative (V).Alternatively,the N-(3-pyridylmethyl) derivative (V) can also be obtained by direct cyclization of diacid (II) with 3-pyridylmethylamine (VI) at 180?C.The debenzylation of (V) to the 3-hydroxy derivative (VII) is performed by hydrogenation with H2 over Pd/C in methanol/THF.Finally,compound (VII) is treated with chlorosulfonamide and NaH in DMF to provide the target sulfamate.

参考文献标题:Use
文献作者:Reed,M.J.; Potter,B.V.L.(Sterix Ltd.)
参考来源:WO 0232409


合成路线:The oxidation of 3-(benzyloxy)estrone (I) with I2 and KOH in refluxing methanol gives 3-(benzyloxy)-16,17-seco-estra-1,3,5(10)-triene-16,17-dioic acid (II),which is cyclized with urea at 180篊 to yield the cyclic imide (III).The alkylation of (III) with propyl chloride (IV) and NaH in DMF affords the N-propyl derivative (V).Alternatively,the N-propyl derivative (V) can also be obtained by direct cyclization of diacid (II) with propylamine (VI) at 180?C.The debenzylation of (V) to the 3-hydroxy derivative (VII) is performed by hydrogenation with H2 over Pd/C in methanol/THF.Finally,compound (VII) is treated with chlorosulfonamide and NaH in DMF to provide the target sulfamate.

合成路线:The oxidation of 3-(benzyloxy)estrone (I) with I2 and KOH in refluxing methanol gives 3-(benzyloxy)-16,17-seco-estra-1,3,5(10)-triene-16,17-dioic acid (II),which is cyclized with urea at 180?C to yield the cyclic imide (III).The alkylation of (III) with 3-(chloromethyl)pyridine (IV) and NaH in DMF affords the N-(3-pyridylmethyl) derivative (V).Alternatively,the N-(3-pyridylmethyl) derivative (V) can also be obtained by direct cyclization of diacid (II) with 3-pyridylmethylamine (VI) at 180?C.The debenzylation of (V) to the 3-hydroxy derivative (VII) is performed by hydrogenation with H2 over Pd/C in methanol/THF.Finally,compound (VII) is treated with chlorosulfonamide and NaH in DMF to provide the target sulfamate.

参考文献标题:D-ring modified estrone derivatives as novel potent inhibitors of steroid sulfatase
文献作者:Fischer,D.S.; Woo,L.W.L.; Mahon,M.F.; Purohit,A.; Reed,M.J.; Potter,B.V.L.
参考来源:Bioorg Med Chem 2003,11(8),1685


合成路线:The oxidation of 3-(benzyloxy)estrone (I) with I2 and KOH in refluxing methanol gives 3-(benzyloxy)-16,17-seco-estra-1,3,5(10)-triene-16,17-dioic acid (II),which is cyclized with urea at 180篊 to yield the cyclic imide (III).The alkylation of (III) with propyl chloride (IV) and NaH in DMF affords the N-propyl derivative (V).Alternatively,the N-propyl derivative (V) can also be obtained by direct cyclization of diacid (II) with propylamine (VI) at 180?C.The debenzylation of (V) to the 3-hydroxy derivative (VII) is performed by hydrogenation with H2 over Pd/C in methanol/THF.Finally,compound (VII) is treated with chlorosulfonamide and NaH in DMF to provide the target sulfamate.

合成路线:The oxidation of 3-(benzyloxy)estrone (I) with I2 and KOH in refluxing methanol gives 3-(benzyloxy)-16,17-seco-estra-1,3,5(10)-triene-16,17-dioic acid (II),which is cyclized with urea at 180?C to yield the cyclic imide (III).The alkylation of (III) with 3-(chloromethyl)pyridine (IV) and NaH in DMF affords the N-(3-pyridylmethyl) derivative (V).Alternatively,the N-(3-pyridylmethyl) derivative (V) can also be obtained by direct cyclization of diacid (II) with 3-pyridylmethylamine (VI) at 180?C.The debenzylation of (V) to the 3-hydroxy derivative (VII) is performed by hydrogenation with H2 over Pd/C in methanol/THF.Finally,compound (VII) is treated with chlorosulfonamide and NaH in DMF to provide the target sulfamate.
参考文献标题:Novel D-ring modified steroid derivatives as potent,non-estrogenic,steroid sulfatase inhibitors with in vivo activity
文献作者:Fischer,D.S.; Chander,S.K.; Woo,L.W.L.; Fenton,J.C.; Purohit,A.; Reed,M.J.; Potter,B.V.L.
参考来源:J Steroid Biochem Mol Biol 2003,84(2-3),343