4-Substituted piperidines. V. Local anesthetic 4-aminoalkoxy-4

Sep 1, 1970 - J. Med. Chem. , 1970, 13 (5), pp 835–838. DOI: 10.1021/jm00299a009. Publication Date: September 1970. ACS Legacy Archive. Note: In lie...
0 downloads 0 Views 406KB Size
Journal of Medicinal Chemistry, 1970, Vol. 13, No. 6 836

&SUBSTITUTED PIPERIDINES. V 8: Uv max 229.5 ( 6 14,600), 246 ( e 12,200); 251 ( e 11,060), 335 ( E 6160), 340 ( e 6270), 388 mp ( E 2620); ir 1660, 1630 cm-I (C=N); mass spectrum m/e 170 (M+); nmr [(CD,)k30] 6 8.91 (s, 1, H-7). 9: Lv max 228 ( e 16,800), 321 ( e 6350), inflecrion 356 nip (E 2450); ir 1635 cm-' (C=N). 10: Uv max 215 ( e 30,050), 298 ( E 11,200), 308 ( e 11,150), iiiflections 222 ( e 27,900); 236 ( e 2400), 253 ( e 6400), 285 mp ( e 8500). ir 1680 cm-I (C=O). 12: Uv max 233 ( E 27,900), 314 ( E 3900), inflection 263 mp ( e 4700); ir 1675, 1650 em-' (C=O). 14: Uv max 228 ( e 21,200), 356 ( e 4850), inflection 260 mp ( E 5700); ir 1635 em-' (C=O). 16: Uv max 232 ( e 21,850), 316 mp ( e 7400); ir 1640 cni-'

(C=O). 18: Uv max 252

( e 12,300), 267 ( e llJIOO), 335 ( e 4200), 401 8050), inflection 224 mp ( e 18,900); mass spectrum vz P 246 (AI+). 20. Uv max 226 (E 22,800)) 250 ( e 7700), 299 mp (E 23.70). 22. Uv max 227 ( e 35,500), 352 (E 6200), inflection 263 nip ( e 7100): ir 1650 cm-I (C=S). 29: Uv max 211 (E 24,000), 250 (E 6950), 293 mp ( e 2300) 31: Uv max 262 (E 16,150), 464 ( e 6800), inflections 224 i e 12,000), 244 (e 11,400), 295 mp ( e 10,000). 36: Uv max 244 ( e 17,350), 342 mp (E 2650). 37: Uv max 222 ( e 32,350), 246 (e 8070), 299 nip ( E 2220). 38: Uv max 219 ( e 28,300), 256 ( E 33,200), 336 ( e 7200), 111flection 285 mp (L 10,150); ir 167; cm-l (C=O): nmr (C13C1,) 6 4.23 (t, 2, J = 8 Hz, H-2), 6 3.57 (q, 2, H--5),6 3.14 (t, 2, J = 8 Hz, H-1); mass spectrum m e 296, 298 (>I+). 40: Uv max 208 ( e 33,800), 215 ( e 33,200), 272 ( e 32,500), 2Q ( e 32,400), 313 (E 1310), 426 ( e 1150), inflections 235 (E 26,500), 262 ( e 24,600), 322 ( e 1195), 340 mp ( e 514); ir 3300 (NH), 1650 em-' iC=O), iimr [(CD3)?SO]6 4.09 (d, 1, J = 2 HI, H 4 ) , 6 8.7.5 ( y , 1, H-7), mit>h spectrum tn ' e 296, 298 (>I+). (E

Uv max 234.5 ( e 31,050), 272 ( e 8600), 281 ( e 7800), 333 3900); ir 3300 (NH),1655 cm-l (C=O). 42: Uv max 220 ( e 28,600), 236 ( e 20,850), 262 ( e 20,3\50),272 ( E 27,150), 282 ( e 27,150), 314 ( E MOO), 425 ( e 1050), inflection 324 mp ( e 16j0); ir 1690 (C=O), 1620 cm-I ( C = S ) . 46: Uv max 243 ( E 24,800), 313 mp ( e 23.N); ir 1670 cm-' (C=O). 48:s' Uv max 343 (E 11,300), iiiflectioiis 223 ( E 1x,300), nip ( e 17,930); 54: Uv max 236 ( E 20,9>0), 323 111p ( e 3150j; ir 1670 cm-' (C=Oj. 57: L-v max 25% ( C 16,630): 30s i e 7230), inflection 31% m p (E 6400); ir 1710 cm-' (C=O): iimr (CDC1,) 6 4.6s ( s j 2, H-5); ma.. 5pectrum m c 260 (AI+). O ) , 304 ( e 6030), iiiflec60: Uv max 246 ( e 20,410), 296 ( E t i o i i 2% nip (E 3290); ir 8340 (NH), 90 em-' (C=O); nmr [iCl)a)rSO] 6 3.49 (s, 1, H-7)] 3.83 ( 5 , 2, H--5). 62: 1-v max 244 ( E Ih,930), 437 (E 6250), iriflection 273 nip f E .>TOO). 64:38 Vv niax 22.5 ( e 19,h00), 2>2 (l%,X.iO), 276 (9800), 356 0); ir 1615 cni-' ( C = S ) ; mass spectrum ill (J 280, 2h2 (>I-). 41:

mp

(E

Acknowledgment.-The author- are indebted t o Dr. E C. 01so11 and hi- ahzociate- for phyqical arid analytical data and to Mr. J. Robert Greene for laborator) a--istance. fX7) The ninr spectrum [ C C U 3 ) 6 0 ] of 62 had peaks a t 6 8.17 ( d . J = 2 I l a ) and 7 . 9 9 [broad singlet) for H-6 and H-4 which thus estblished t h e location of t h e S O ! . ( 3 8 ) T h e ninr spectrum [ ( C l ) d n S O I of 64 was essentially the same as t h a t of 18 except t h a t in 64 11-1 ( 6 6.89, d. J = 3 Hz) was absent and H-2 v a s represented I)?. a singlet a t 8.01.

4- Substituted Piperidines.

Local Anesthetic 4-Aminoalkoxy -4-arylpiperidines

BERTHERMANS, HCGOYEHHOEVEK, Janssen Pharniaceutica

12.2'.,

AND P A U L

JASSSEX

Research Laborafol ia,8340 Bcerse, Belgium

Keceiced A p r i l

4,197'0

The synthesis of a new series of 4,4-disubstituted piperidines is described. These 4-aminoalkoxy-4-arylpiperidines are obtained by performing successively a Grignard reaction on .l*-carbethoxy-4-piperidone, transformation of the tertiary alcohol in an ether, decarbethoxylation, and finally reaction of the secondary amine with a halide. The compounds are good local conduction anesthetics in laboratory animals.

I n previous publications1 of thiq serie.: the synthesis and pharmacological activity of several 4,4-disubstituted and 4-monosubstituted piperidines were described. One of the most important series was that of the n-ellknon 11 4-aryl-4-hydroxypiperidine compound