Diampromide , Hive Methods Discourse


Cyrax (Hive Bee) 10-09-02 03:58 No 366431	Diampromide (Rated as: excellent)	Bookmark
	Diampromide was develloped at the American Cyanamid Company, by some chemists who modified the methadone molecule a bit. Preliminary clinical results indicate that the potency of diampromide lies between that of meperidine and morphine. Synthesis: A benzene solution of N-methylphenethylamine⁽¹⁾ and 2-bromopropionanilide⁽²⁾ was heated under reflux to give 2-(N-methylphenethylamino)-propionanilide in 81 % yield (M.P.: 65- 67 °C). The reduction of 2-(N-methylphenethylamino)-propionanilide with LiAlH₄in THF afforded 80 % of N²-methyl-N²-phenethyl-N¹-phenyl-1,2-propanediamine (B.P.: 138 - 144 °C / 0.2 mm Hg). When N²-methyl-N²-phenethyl-N¹-phenyl-1,2-propanediamine was acylated with propionic anhydride N-[2-(methyl-phenethylamino)-propyl]-propionanilide was obtained in 83 % yield (B.P.: 174 - 178 °C / 0.5 mm Hg). The sulphate salt crystallized from EtOH - Et₂O in 85 % yield (M.P.: 110 - 111 °C). Precursors: ⁽¹⁾ J. Chem. Soc. (1910) p 2253 ⁽²⁾ Ber. (1892) vol 25 p 2919 Ref.: JACS (1959) vol 81 p 1518 - 1519 A comparison between diampromide, 2,3-seco-fentanyl and fentanyl can be found at: http://www.ch.ic.ac.uk/ectoc/echet98/pub/028/index.htm Diampromide seems to be 167 times less potent than fentanyl. Hence, I estimate that the dose would be 4 - 8 mg.



Bwiti (PVC-Analog Taste-Tester) 10-09-02 04:18 No 366435	Sweet! I wonder if Na-borohydride/nickel boride ...	Bookmark
	Sweet! I wonder if Na-borohydride/nickel boride could replace the LAH? If diampromide is more euphoric and less sedating than prodine or analogs, then it would be worth making. Peace! Love my country, fear my government.



Cyrax (Hive Bee) 10-09-02 10:26 No 366541	refs. (Rated as: excellent)	Bookmark
	I don't know if the P-2 catalyst (normally used to reduce alkenes) can be used to reduce amides ... But I have refs. for coreactants that can be used with NaBH₄ to reduce amides: * Tetrahedron Lett. (1969) p 4555 * Tetrahedron Lett. (1976) p 219 * J.Org. Chem. (1977) vol 42 p 2082 * J.Org. Chem. (1981) vol 46 p 2579 * Synthesis (1987) p 1128 * Chem. Lett. (1990) p 251 Mabey Ni₂B is one of them. I know it will work with BF₃ or Me₃SiCl as a coreagent. BF₃ + NaBH₄ will in situ generate borane (cfr. J. Org. Chem. (1973) vol 38 p 912). And trichlorosilane even reduces amides without NaBH₄. Ref.: Chem. Lett. (1972) p 989. What looks promessing, is that all kinds amides can be reduced with Na in 1-propanol. However, the article is somewhat difficult to obtain: Chem. Ind. (London) (1990) p 547. Bwiti, I would say: up to the library .