Ranitidine

Chemical Name N-[2-[ [[5-(Dimethylamino)methyl-2-furanyl] methyl] thio] ethyl] -N -methyl-2-nitro-1,1 -ethenediamine 

Trade Name Manufacturer Country Year Introduced 

N-methyl-1-(methylthio)-2-nitroetheneamine (230 g) in water (400 ml) was stirred and heated at 45°C to 50°C. 2-[ [ [5-(Dimethylamino)methyl-2-furanyl] methyl] thio] ethanamine (321 g) was added dropwise over 4 hours and the resuitant solution stirred for a further 3 A hours. 

Trade Name Ma nufacturer Country Year Introduced 

The solution was then heated at reflux for A hour, cooled to 70°C and 4-methylpentan-2-one (2 liters) added. The water was removed by azeotropic distillation under reduced pressure (260 torrs) and the resultant solution treated with charcoal (10 g) at 50°C. The solution was filtered and cooled to 10°C. N-[2-[ [ [5-dimethylamino)methyl-2-furanyl] methyl] thio] ethyl] -N -methyl-2-nitro-1,1 -ethenediamine (380 g) was filtered off and dried, melting point 69°C to 70°C. 

2-(((5-(Dimethylamino)methyl-2-furanyl] methyl] thiol ethanamine Manufacturing Process 

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Therapeutics. Compounds containing the furan or tetrahydrofuran ring are biologically active and are present in a number of pharmaceutical products. Eurfurjdamine [617-89-0] is an intermediate in the diuretic, furosemide. Tetrahydrofurfurylamine [4795-29-3] may also have pharmaceutical applications. 5-(E)imethyiaininomethyi)furfuryi alcohol [15433-79-17 is an intermediate in the preparation of ranitidine, which is used for treating ulcers. 2-Acet5dfuran [1192-62-7] prepared from acetic anhydride and furan is an intermediate in the synthesis of cefuroxime, a penicillin derivative. 2-Euroic acid is prepared by the oxidation of furfural. Both furoic acid [88-14-2] and furoyl chloride [527-69-5] are used as pharmaceutical intermediates. 

Fig. 2. A stick drawing of the dmg Zantac (ranitidine) illustrating the method of showing color-coded electronic charge data (color not shown here), where...

Fig. 3. CPK (Corey-Pauhng-Koulton) rendering displaying shaded soHd surface for ranitidine, normally color-coded according to atom types (black representing carbon green, hydrogen yellow, sulfur blue, nitrogen and red, oxygen colors not shown here).

Fig. 5. A representation of ranitidine displaying four layers of the Connolly solvent-accessible dot surface normally color-coded in this process to correspond with the energies of electrostatic potential (color not shown here). Thus, the highest charge density would be indicated by red dots representing points where the attraction to an atom is strongest, and conversely, purple points would signify regions of maximal positive charge.

Fig. 6. Two representations of ranitidine illustrating the electrostatic potential mapped onto (a) a soHd and (b) translucent constant-density surface (0.001...

Fig. 7. Graphical representations of (a) the Highest Occupied Molecular Orbital (HOMO) and (b) the Lowest Unoccupied Molecular Orbital (LUMO) for ranitidine. It is possible, in the ordinarily visible color-coded data not shown here, to distinguish the strong localization (a) of the HOMO to the sulfur atom and adjacent nitroethyleneamine fragment and the contrasting localization (b) of the LUMO to the nitroethylenearnine fragment. Neither the LUMO not HOMO appear to have contributions from the dimethylaminomethyl-suhstitiited furan.

Ranitidine. Ranitidine hydrochloride [66357-59-3] (Zantac) is a white to pale yellow granular substance. It is freely soluble in water and acetic acid, soluble in methanol, sparingly soluble in ethanol, and practically insoluble in chloroform. It has a slightly bitter taste and a sulfur-fike odor. It may be made by the method described in Reference 5. 

The sales of antagonists of receptors, eg, diphenhydramine, terfenadine, and astemizole, used in the treatment of allergic diseases, represent 1% of the overall pharmaceutical market, ie, 1.7 biUion (U.S.). antagonists, eg, cimetidine and ranitidine, are effective in peptic ulcer disease and esophageal reflux. Sales represent 3.5% of the world market, ie, 6 biUion (U.S.). agonists or antagonists have not yet found a clear indication. 

Nitromethane also is used in the synthesis of the antiulcer dmg, ranitidine [66357-35-5]. A two-step process utilizing nitromethane, carbon disulfide, potassium hydroxide, and dimethyl sulfate yields l,l-bis(methylthio)-2-nitroethene [13623-94 ] which reacts further to produce ranitidine. 

Racemoramide 1, 82 Racemorphan 293 Ranitidine 2 131 Reproterol 3, 231 Rescinnamine U 319 Rimantadine 19... 

Etintidine (84), an imidazole-containing histamine H-2 receptor antagonist, is an antiiilcer agent conceptually related to cimetidine and ranitidine. It can be synthesized by various routes one of which terminates by an addition-elimination reaction of propargylamine with substituted N-cyano-S-methylisothiourea derivative 83 to give etintidine (84) [28]. 

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