Azasteroids. Part VII. Synthesis of 7-hydroxy-2-methoxy-7,8,9,10-tetrahydrobenzo[i]phenanthridine

Abstract

O-tetrahydrobenzo[i]phenanthridine (XI) has been synthesised by a new route. Its N-oxide rearranges on heating with acetic anhydride to give the 7-acetoxy-derivative which is then hydrolysed to afford the title compound.

Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) Toward Inhibition of Phenylethanolamine N-Methyltransferase vs the α2-Adrenoceptor1a

“…The organic layer was dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure to yield a yellow oil. The oil solidified on standing and was crystallized from aqueous EtOH as pale buff needles (4.95 g, 80.6%, mp 66-67 °C): IR (KBr) 1685 (CO), 1520 (NO2), 1460, 1340 (NO2), 1200, 1140, 890 cm -1 ; 1 H NMR (CDCl3) δ 8.15-8.05 (m, 2 H, H-7, H-8), 7.40-7.32 (m, 1 H, H-6), 4.90-4.85 (m, 2 H, H-1), 4.00-3.89 (m, 2 H, H-3), 3.10-3.06 (m, 2 H, H-4); EIMS m/z (relative intensity) 275 (M + + 1, 16), 274 (M + , 100), 259 (10), 227 (25), 162 (14), 149 (35), 130 (15), 116 (26), 115 (30), 103 (28), 102 (14), 91 (31), 77 (69), 69 (45), 51 (34). Anal.…”

“…The difficulty in cyclization at the β-position on naphthalene is due to its low reactivity . Hence, another approach based on the synthesis of azasteroids was adopted . Commercially available 6‘-methoxy-2‘-propiononaphthone was converted to the 6‘-methoxy-2‘-naphthylpropionic acid ( 25 ) by the Willgerodt reaction .…”

“…24 Hence, another approach based on the synthesis of azasteroids was adopted. 25 Commercially available 6′-methoxy-2′-propiononaphthone was converted to the 6′-methoxy-2′-naphthylpropionic acid (25) by the Willgerodt reaction. 26 This acid was subjected to the Curtius reaction protocol (Scheme 3), and the intermediate isocyanate was cyclized to 26 by heating with BF 3 ‚Et 2 O.…”

“…Purification by PCTLC (silica gel, 4 mm) using CH2Cl2-MeOH-NH4OH (250:17:1) as the eluent yielded compound 19 as a colorless foam (2.37 g, 76.9%). Crystallization of this foam from CH2Cl2-hexanes afforded pale yellow crystals: mp 109-110 °C; IR (KBr) 3430 (NH2), 3360 (NH2), 1480, 1440, 1030, 740, 705 cm -1 ; 1 H NMR (CDCl3) δ 7.56-7.54 (m, 6 H, ArH), 7.27-7.05 (m, 12 H, ArH), 3.73 (s, 2 H, H-1), 3.45 (bs, 2 H, ArCH2NH2), 2.98-2.96 (m, 2 H, H-3), 2.52 (bs, 2 H, H-4), 1.49 (bs, e, 2 H, NH2); 13 C NMR (CDCl3) δ 142.2, 140.1, 136.1, 133.2, 129.0, 128.6, 127.3, 125.8, 125.0, 124.6, 76.4 (CPh3), 50.6 (C-1), 46.2, 45.9, 29.4 (C-4); EIMS m/z (relative intensity) 404 (M + , 0.3), 327 (M + -Ph, 4), 243 (Ph3C + , 91), 165 (100), 132 (25), 115 (26), 91 (56), 77 (35), 51 (27) in an ice bath, and triethylamine (0.58 g, 0.79 mL, 5.7 mmol) was added. After addition of mesyl chloride (0.65 g, 0.45 mL, 5.4 mmol), the mixture was stirred at room temperature for 16 h. The reaction was quenched with 1 N NaOH and extracted with CH2Cl2 (four times).…”

Synthesis of Dibenzo[c,h][1,6]naphthyridine, [2]Benzopyrano[4,3-c]quinoline and Benzo[i]phenanthridine Analogues of the Quaternary Benzo[c]phenanthridines

“…Various synthetic routes have been developed, but most tend to suffer from lengthy approaches and low overall yields. [18][19][20][21][22][23] The exception was the method developed by Rigby and Balasubramanium, 24,25 which involved the cyclocondensation reaction between 1-cyclohexenyl isocyanate and the pyrrolidine enamine of b-tetralone to give the 7,8,9,10,11,12-hexahydrobenzo[i]phenanthridin-5(6H)-one in 61% yield. We have modified this approach (Scheme 2) by employing the Reverse-Vilsmeier synthesis of quinolinium salts pioneered by Meth-Cohn and Taylor.…”