Naphthalenes and biphenyls via a novel reaction of N,N-dimethylformamide dimethyl acetal

Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 1. Identification of the 4-Quinolinecarboxamide Framework

“…N -(Dimethylamino)-2-phenyl-4-naphthalenecarboxamide (23). Diphenylacetone ( 21 ; 23.8 mmol) and N , N -dimethylformamide dimethyl acetal ( 22 ; 0.15 mol) were heated in a steel autoclave at 180 °C for 24 h under nitrogen atmosphere; the reaction mixture was then diluted with a mixture of Et 2 O/hexane (1:5) and stirred for 1 h. The precipitate was filtered, washed with hexane, and dried to afford 23 (14.9 mmol, 63%) as white needles: 137−138 °C (lit …”

“…The 2-phenylnaphthalene-4-carboxamide derivative 74 was synthesized according to Scheme . In this scheme, a mixture of 1,3-diphenylacetone ( 21 ) and N , N -dimethylformamide dimethyl acetal ( 22 ) was heated in a steel autoclave at 180 °C for 24 h according to the procedure described by R. F. Abdulla et al . to give the dimethylamide 23 .…”

“…The 2-phenylnaphthalene-4-carboxamide derivative 74 was synthesized according to Scheme 5. In this scheme, a mixture of 1,3-diphenylacetone (21) and N,Ndimethylformamide dimethyl acetal (22) was heated in a steel autoclave at 180 °C for 24 h according to the procedure described by R. F. Abdulla et al 36 and acetonitrile with POCl 3 for 29 h. 37 Subsequent oxidation of the aromatic methyl group to the corresponding carboxylic acid was achieved in three steps. 38 Firstly, the methyl was converted into the dibromomethyl group with N-bromosuccinimide (NBS); then, the aldehyde derivative 28 was obtained by neutral silver nitrate oxidation in refluxing EtOH/H 2 O/THF, and finally, the oxidation was completed by stirring 28 at room temperature with an excess of silver nitrate under basic conditions.…”

“…4-Chloro-7-methoxy-2-phenylquinoline (17). 4-Hydroxy-7-methoxy-2-phenylquinoline (16; 43.6 mmol) was refluxed in POCl3 (120 mL) for 2 h; the solvent was evaporated, and the residue was taken up with 10% NaOH and extracted with EtOAc; the organic layer was dried over Na2SO4 and the solvent evaporated to afford 17 (29.6 4-(Benzylamino)-7-methoxy-2-phenylquinoline (36). A mixture of 4-chloro-7-methoxy-2-phenylquinoline (17; 3.7 mmol), benzylamine (3.7 mmol), and phenol (4.6 g) was heated at 150 °C for 3 h; after cooling, CH2Cl2 (20 mL) and 0.1 N NaOH (20 mL) were added to the reaction mixture; the organic layer was washed with 0.1 N NaOH until disappearance of phenol, dried over Na2SO4, and evaporated.…”