Sam, Joseph’s team published research in Journal of the American Chemical Society in 81 | CAS: 530-40-5

Sam, Joseph published the artcileHypotensive agents. Pyridinecarboxamides and piperidinecarboxamides, Related Products of amides-buliding-blocks, the publication is Journal of the American Chemical Society (1959), 710-13, database is CAplus.

Nicotinic acid (100 g.) in 2 l. CH₂Cl₂ treated gradually with 81 g. Et₃N, the mixture treated at 0-5° with 95 g. ClCO₂Et during 15-20 min., kept 0.5 hr. at 0°, treated with 57 g. pyrrolidine at 0-5°, warmed to room temperature, after 2 hrs. washed twice with 150 cc. H₂O, and distilled gave 90 g. 1-nicotinoylpyrrclidine, b_0.3 131-3°; methiodide m. 213.5-14.5° (MeCN), 87% yield. Similarly were prepared the following compounds (b.p./mm. and % yield given): N,N-diethylamide of isonicotinic acid (I), 109°/0.5 62; morpholide (II) of I, 142-5°/0.4, 55 [II.PhCH₂CH₂Br m. 214-15° (MeOH-Me₂CO), 97%]; morpholide (III) of nicotinic acid (IV), 190-5°/0.4, 48 [III.PhCH₂CH₂Br m. 212-13° (MeOH-Et₂O), 95%]; morpholide (V) of pyridine-2-carboxylic acid (VI), 142-3°/1, 59 [VI.MeI m. 175-6° (MeOH), 81%]; 2,6-dimethylmorpholide of IV, 138-40°/0.5, 57; 2,6-dimethylmorpholide (VII) of I, 135-7°/0.3, 50 [VII.PhCH₂CH₂Br m. 227-8° (MeOH-Et₂O), 94%]; 2,6-dimethylpiperidide of I, – (m. 73-4°), 20; 4-methylpiperazide of I, 133-5°/0.4, 39; p-ethoxyanilide (VIII) of IV, – (m. 170-5°), 50 [VIII.MeI m. 194-6°, 92%; VIII.PhCH₂CH₂Br m. 243-4° (MeOH), 88%]; p-dimethylaminoanilide (IX) of VI, -, 60 [IX.2HCl m. 227-30° (decomposition); IX.MeI m. 229-30° (decomposition)(MeOH), 98%]; p-dimethylaminoanilide (X) of IV, – (m. 185-7°), 25 [X.MeI m. 230-5° (decomposition)(MeOH), 95%]; p-dimethylaminoanilide (XI) of I, -, 38 [X.2HCl m. 175° (decomposition); X.MeI m. above 200° (decomposition)(MeOH), 90%]. The appropriate pyridinecarboxamide in MeOH or MeCN refluxed 24 hrs. with 10-20% suitable halide, the resulting quaternary salts in H₂O or EtOH hydrogenated over PtO₂ (0.3 g./0.1 mole) at 50-60 lb. during 15-30 hrs., filtered, basified strongly with 50% aqueous NaOH, extracted with Et₂O, and the extract worked up yielded the corresponding piperidinecarboxamide. N,N-Diethylnipecotamide (XII) (19 g.), 20 g. PhCH:CHCH₂Br, and 20 g. K₂CO₃ in 200 cc. PhMe refluxed 3 hrs. with stirring, cooled, washed with H₂O, dried, and distilled yielded 27 g. 1-cinnamyl derivative of XII, b_0.4 184-7°. Similarly were prepared the following 1-substituted piperidinecarboxamides (b.p./mm. and % yield given): 1-Ph(CH₂)₂ deriv, of XII, 173°/0.3, 86 (n²⁷_D 1.5221); 1-Ph₂CH derivative of XII.HBr, -, 20 [m. 234.5-35° (MeOH)]; 1-PhCH₂ derivative of the 4-isomer of XII, 173-5°/0.7, 87; 1-Me derivative of the pyrrolidide (XIII) of nipecotic acid (XIV), 111-14°/0.3, 89; 1-PhCH₂CH₂ derivative of XIII, 181-3°/0.1, 62 (n²⁵_D 1.5431); morpholide (XIV) of piperidine-2-carboxylic acid (XV), 143-5°/1.5, 65; 1-Me derivative of XIV, 121-3°/0.8, 87 (n³²_D 1.5013); 1-PhCH₂CH₂ derivative of XIV, 192-5°/0.4, 16 (n²⁴_D 1.5426); 1-Me derivative of the morpholide (XVI) of XIV, 118°/0.2, 72 (n^25.5_D 1.5065); 1-PhCH₂ derivative of XVI, 183-6°/0.3, 80; 1-PhCH₂CH₂ derivative of XVI, 188-92°/0.2, 85 (n³⁴_D 1.5406); 1-Ph(CH₂)₃ derivative of XVI, 203-6°/0.3, 71; 1-PhCH₂CH₂ derivative (XVII) of the morpholide of isonipecctic acid (XVIII), -, 85 [XVIII.HBr m. 279-80° (MeOH)]; 1-PhCH₂CH₂ derivative of the 2,6-dimethylmorpholide of XIV, 188-90°/0.2, 50 (n^24.5_D 1.5327); 1-PhCH₂CH₂ derivative (XIX) of the 2,6-dimethylmorpholide of XVIII, -, 78 [XIX.HBr m. 252-4° (H₂O)]; 1-Me derivative of the p-ethoxyanilide (XX) of XIV, -, 77 [m. 122-3° (aqueous MeOH)]: 1-PhCH₂CH₂ derivative (XXI) of XX, -, 82 [XXI.HBr m. 108-10° (decomposition) (Me₂CO)]; p-dimethylaminoanilide (XXII) of XV, -, 93 [m. 127-30° (aqueous MeOH)] [XXII.2HCl m. 248-50° (decomposition)(MeOH)]; p-dimethylaminoanilide (XXIII) of XVIII, [m. 197-8° (MeOH)], 90 [XXIII.2HCl m. 252-4° (decomposition) (MeOH)]. The appropriate 1-methylpiperidinecarboxamide reduced with LiAlH₄ yielded the corresponding alkylaminomethyl derivatives of 1-methylpiperidine (alkylamino group, b.p./mm., % yield, m.p., and % yield of dimethiodide given): 3-pyrrolidino, 59°/0.3, 93, 264-6° (decomposition), 94(at 25° in MeCN); 2-morpholino, 79-82°/0.4, 63, 255-6° (decomposition), 55 (refluxed 6 hrs. in MeCN); 3-morpholino, 87-8°/0.8 (n^25.5_D 1.5202), -, 281-2° (decomposition), – (refluxed 6 hrs. in MeOH). 1-Nicotinoylpyrrolidine in Et₂O reduced with LiAlH₄ yielded 44% 3-pyrrolidinomethylpyridine, b_0.2 75-7°, n^25.5_D 1.5202. XII (27.6 g.) and 18.2 g. styrene oxide heated 18 hrs. on the steam bath, the mixture dissolved in Et₂O and extracted with 6N HCl, the extract neutralized with NaOH and extracted with Et₂O, and the extract worked up gave 32.2 g. N,N-diethyl-1-(2-hydroxy-2-phenylethyl)nipecotamide, b_3.5 228-30°. XII (27.6 g.), 23.6 g. p-O₂NC₆H₄Cl, and 20.2 g. Et₃N heated 20 hrs. on the steam bath, cooled, triturated with H₂O, and filtered gave 45.1 g. N,N-diethyl-1-(p-nitrophenyl)nipecotamide (XXIV), m. 99.5-101.5° (EtOH). XXIV (15.3 g.) in 200 cc. EtOH hydrogenated at room temperature and 50 lb. over Raney Ni during 15 min., filtered, evaporated, the residue dissolved in Et₂O, and the solution saturated with dry Et₂O yielded 50% p-NH₂ analog di-HCl salt of XXIV, m. 227.5-8.5° (MeOH-EtOAc). 3-(3-Pyridyl)-acrylic acid (prepared in 79% yield from 3-pyridinecarboxaldehyde and malonic acid) treated in the usual manner with ClCO₂Et and morpholine in CH₂Cl₂ yielded 79% 4-[3-(3-pyridyl)acrylyl]morpholine (XXVI), m. 141-3° (MeCN). XXVI in MeOH hydrogenated at 60 lb. over 5% Pd-C yielded 87% 4-[3-(3-pyridyl)propionyl]morpholine (XXVII), b₁ 188-90°, n^24.5_D 1.5457. XXVII and excess PhCH₂CH₂Br in MeCN refluxed 18 hrs., the MeCN removed in vacuo, the residual oil dissolved in H₂O, the solution hydrogenated over PtO₂ at 60 lb. and 50°, and the mixture worked up in the usual manner yielded 84% 4-[3-(1-phenethyl-3-piperidyl)propionyl]morpholine, b_0.3 217-19°.

Journal of the American Chemical Society published new progress about 530-40-5. 530-40-5 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N,N-Diethylisonicotinamide, and the molecular formula is C10H14N2O, Related Products of amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics