197449-60-8Relevant academic research and scientific papers
Tetracyclic spiro compounds as 5HT1B receptor antagonists
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, (2008/06/13)
PCT No. PCT/EP97/01404 Sec. 371 Date Sep. 18, 1998 Sec. 102(e) Date Sep. 18, 1998 PCT Filed Mar. 19, 1997 PCT Pub. No. WO97/34901 PCT Pub. Date Sep. 25, 1997Compounds of formula(I) where B is oxygen or sulphur, D is nitrogen, R6 and R7 forms a ring, m is 2, R is a substituted latam ring of formula (i) where p is 1, P is a substituted or unsubstituted bicyclic ring containing one or two heteroatoms or P is an unsbustituted or substituted 5- to 7-memebered saturated ring containing one or two heteroatoms; X, Y, Z, E, G, R3, R4, R5, R8, R9, and R10 are as defined in the specification.
Multikilogram-scale synthesis of a biphenyl carboxylic acid derivative using a Pd/C-mediated suzuki coupling approach
Ennis, David S.,McManus, Julie,Wood-Kaczmar, Wladyslaw,Richardson, John,Smith, Gillian E.,Carstairs, Alexis
, p. 248 - 252 (2013/09/08)
Reaction of 4-bromo-3-methylaniline with 4-chlorobutyryl chloride/TEA and subsequent treatment of the resulting secondary amide intermediate with KOt-Bu gives 1-(4-bromo-3methylphenyl)pyrrolidin-2-one in 65% yield. This procedure has been optimised (74-76% overall yield) and has been carried out on 41 molar scale. In a variation of this process, we have employed NaOH as the ring-closing base under phase-transfer conditions. NaOH is added to a mixture of 4-bromo-3-methylaniline, 4-chlorobutyryl chloride, and catalytic TBAC in THF/ H2O. A further 2 equiv of aqueous NaOH is added, and the mixture is heated at 40-45 °C, providing access to cyclised product in an improved 86% yield. 1-(4-Bromo-3-methylphenyl)pyrrolidin-2-one is subsequently coupled with 4-carboxyphenylboronic acid under standard Suzuki coupling conditions [Pd(PPh3)4, Na2CO3, DME/H2O] to give 2′-methyl-4′-(2-oxo-1-pyrrolidinyl)biphenyl-4-carboxylic acid in 64% yield, contaminated with 40-80 ppm of residual Pd. In a modification of this process, we have used Pd/C as the catalyst. Reaction in MeOH/ H2O gives an improved yield of the biphenylcarboxylic acid with residual Pd levels of a one-pot procedure, providing access to 2′-methyl-4′-(2-oxo-1-pyrrolidinyl)biphenyl-4-carboxylic acid in 82% overall yield from 4-bromo-3-methylaniline.
