Suprofen, TYN-762P(as Poultice), R-25061, Profenal, Suprol, Suprocil, Maldocil

舒洛芬Chemical Name: p-(2-Thenoyl)-hydratropic acid; alpha-Methyl-4-(2-thienylcarbonyl)benzene acetic acid
CAS No. 40828-46-4
项目整合开发状态: Withdrawn-1999
项目研究机构: Cilag (Originator), Janssen (Originator), Taiyo (Originator), Alcon (Licensee)
合成路线:The reaction of 2-thiophenecarbonyl chloride (I) with fluorobenzene (A) by means of AlCl3 gives (4-fluorophenyl)(2-thienyl)ketone (II),which is then condensed with diethyl methylmalonate (B) by means of NaH in benzene-HMPA to yield diethyl 2-methyl-2-[4-(2-thienylcarbonyl)phenyl]malonate (III); this product is finally hydrolyzed and partially decarboxylated with refluxing aqueous NaOH.

合成路线:The reaction of 1-(4-bromophenyl)ethanol (IV) with 3,4-dihydro-2H-pyran (C) by means of HCl yields 2-[1-(4-bromophenyl)ethoxy]tetrahydro-2H-pyran (V); this product by condensation with 2-thiophenecarbonitrile (D) through its Grignard complex in THF gives [4-(1-hydroxyethyl)phenyl](2-thienyl)ketone (VI),which without purification is treated with SOCl2 in benzene to give [4-(1-chloroethyl)phenyl](2-thienyl)ketone (VII); then the halogen is substituted by CN with NaCN in DMSO to afford alpha-methyl-4-(2-thienylcarbonyl)benzeneacetonitrile (VIII),which,without purification,is hydrolyzed with H2SO4 and acetic acid.

合成路线:The condensation of thiophene (E) and 4-ethylbenzoyl chloride (IX) by means of SnCl4 in CH2Cl2 gives (4-ethylphenyl)(2-thienyl)ketone (X),which is brominated with N-bromosuccidine and benzoyl peroxide in CCl4 to [4-(1-bromoethyl)phenyl](2-thienyl)ketone (XI); then this product is treated with NaCN in DMSO to obtain the acetonitrile (VIII),which,without purification,is hydrolyzed with H2SO4 and acetic acid.