Synthesis of 2,3,4,5‐tetrahydro‐7,8‐dimethoxy‐1H‐2‐benzazepines

Gold(I)-Catalyzed Benz[c]azepin-4-ol Synthesis by Intermolecular [5 + 2] Cycloaddition

“…29b The benzylic activation seems to be crucial, as all benzaldimine substrates 2a−g readily afforded cycloaddition, while the corresponding C-alkylimine substrates 2h and 2h′ (entry 16, Table 2) failed to undergo [2 + 5] cycloaddition, in accordance with nonsuccessful acid-catalyzed Pictet−Spengler benzazepine cyclization of aliphatic aldimines. 30 The application of N-ethylbenzaldimine 2g (entry 15) in the new benzazepine synthesis demonstrates the versatility of the new cyclization reaction.…”

“…1 H NMR (300 MHz, CDCl 3 ) δ (ppm) 8.10 (m, 2 H arom ), 7.12−7 30. (m, 7 H arom ), 6.87 (d, J = 8.1 Hz, 2 H arom ), 6.79 (d, J = 7.2 Hz, 2 H arom ), 6.01 (s, 1 H, CH C), 5.47 (s, 1 H, CHN), 3.92 (d, J = 16.2 Hz, 1 H, CH 2 ), 3.79 (d, J = 15.9 Hz, 1 H, CH 2 ), 3.50 (s, 3 H, (OCH 3 ); 13 C NMR (100 MHz, CDCl 3 δ (ppm) 158.1 (1 C, CCOCH 3 ), 150.2 (1 C, C arom ), 149.1 (1 C, C arom ), 147.0 (1 C, C arom ), 136.1 (1 C, C arom ), 135.2 (1 C, C arom ), 130.9 (1 C, CH arom ), 130.7 (1 C, CH arom ), 129.3 (2 C, CH arom ), 128.8 (2 C, CH arom ), 128.2 (1 C, CH arom ), 125.6 (1 C, CH arom ), 123.4 (2 C, CH arom ), 118.9 (1 C, CH arom ), 114.6 (2 C, CH arom ), 102.1 (1 C, CCH), 68.2 (1 C, CHN), 55.0 (1 C, OCH 3 ), 48.3 (1 C, CH 2 ); IR (neat, cm −1 ) 2931, 1251, 1089; HRMS (EI) calcd for C 23 H 20 O 3 N 2 372.1466, obsd 372.1466.…”

Synthesis of fused heterocycles: 1,2,3,4-tetrahydroisoquinolines and ring homologues via sulphonamidomethylation

“…The title heterocycles (3) have been obtained by a two-step synthesis; namely an initial intramolecular sulphonamidomethylation of N-aralkylsulphonamides (1 ) in acid media followed by desulphonylation of compounds (2) under moderate conditions, either by reduction or acid hydrolysis. Generally both steps gave good or high yields of compounds (3) variously substituted in the aromatic ring and with a six-, seven-, or eight-membered heterocyclic ring.…”

Multi-Kiloscale Enantioselective Synthesis of a Vitronectin Receptor Antagonist

“…In a method that did not construct the benzazepinone ring system through C−N bond formation, researchers at Merck modified the Pictet−Spengler reaction (usually reserved for isoquinoline synthesis) and cyclized onto an acylimine (eq 3, Scheme ). Other researchers as well have used subtle variations on Pictet−Spengler chemistry to afford the desired benzazepinone skeleton. , The Schmidt, and Beckman, rearrangements of β-tetralones may also be used to prepare 2-benzazepin-3-ones 1 Alternate Methods of Benzazepinone Synthesis …”

“…Other researchers as well have used subtle variations on Pictet-Spengler chemistry to afford the desired benzazepinone skeleton. 11,12 The Schmidt, and Beckman, rearrangements of β-tetralones may also be used to prepare 2-benzazepin-3-ones. 13 As mentioned above, our synthetic design of SB-273005 hinged upon the construction of an asymmetric synthesis of an appropriate ortho substituted benzylamine intermediate (which would come about via reductive amination) but additionally relied upon Mitsunobu coupling (if not some other classical means) of the newly prepared chiral 2,4,9trisubstituted benzazepinone to a 2,6-disubstituted pyridyl alcohol (Scheme 2).…”