2-Methyl-3-dimethylaminopropyl chloride

The mixture is heated at reflux for two hours with continual agitation and there is then added dropwise a solution of 2-methyl-3-dimethylaminopropyl chloride in an equal volume of Xylene. The mixture is then heated for fifteen hours, after which time it is cooled and decomposed by the cautious addition of ice water. The layers are separated and the aqueous layer extracted with ether. The combined organic layers are next extracted with 10% hydrochloric acid and the acidic extracts then rendered alkaline by the addition of ammonium hydroxide. The precipitated oil is extracted three times with chloroform. The chloroform extracts are dried and concentrated in vacuo, the residue being distiiled to yield the product. 

Indazoles can be considered as either azaindoles or azaisoindoles depending on the reader s prejudice. Benzydamine (54) represents a drug with this heterocyclic nucleus. Alkylation of the amine of anthranilic acid methyl ester with benzyl chloride in the presence of sodium acetate gives 52. Treatment with nitrous acid leads to the nitrosoamine, which cyclizes spontaneously to the 3-ketoindazole system, 53. This intermediate forms an ether of its enol form on heating the sodium salt with 3-dimethylaminopropyl chloride. There is thus obtained benzydamine (54), a fairly potent nonsteroidal antiinflammatory agent with significant antipyretic and analgesic properties. 

The methylene group of anthrone 64 is acidic by virtue of doubly vinylic activation by the carbonyl group. Thus, treatment with methyl iodide and base leads to the 9,9-dimethyl derivative 65. Grignard reaction with 6-dimethylaminopropyl magnesium chloride... 

Copolymers. Copolymers have also been studied (16-18). While one comonomer contains 1-2 quaternary nitrogen in a flexible pendant chain, the other comonomer was nonionic. Copolymers of the methyl chloride salt of dimethylaminoethyl methacrylate (one quaternary nitrogen atom) and dimethylaminoethyl methacrylate (DMAEMA) and of MDTHD (2 quaternary nitrogen atoms) and DMAEMA, N,N-dimethylacryl-amide (NNDMAm) or dimethylaminopropyl methacrylate (DMAPMA) have been studied and the results summarized in Table VI. 

Bromo-l-(4-fluorophenyl)-l-(3-dimethylaminopropyl)-l,3-dihydroisobenzofuran Magnesium Butyl lithium tert-Butyl methyl ether Isopropylmagnesium chloride Thionyl chloride Sulfamide Dry ice... 

The synthesis of bufotenine itself followed closely upon the proof of its structure. Hoshino and Shimodaira reduced the ethyl ester of 5-ethoxy-indole-3-acetic acid by the Bouveault-Blanc procedure to the corresponding primary alcohol, which was treated with phosphorus tribromide and then dimethylamine, to give the ethyl ether of bufotenine, which was demethylated with aluminum chloride (130). In a later synthesis, 2,5-dimethoxybenzyl cyanide (XXIII) was alkylated by Eisleb s method with dimethylaminoethyl chloride in the presence of sodamide to give l-(2,5-dimethoxyphenyl)-3-dimethylaminopropyl cyanide (XXIV), which was then hydrogenated over Haney nickel to yield 2-(2,5-di-methoxyphenyl)-4-dimethylaminobutylamine (XXV R = Me). De-methylation of this with hydrobromic acid, followed by oxidation of the product (XXV R = H) with potassium ferricyanide yielded bufotenine (XIX) via the related quinone (109). 

Nonionic, anionic, and cationic VP copolymers are all available commercially to enhance the hydrophilic, hydrophobic, and ionic properties of PVP for specihc applications. Important comonomers include vinyl acetate (VA), acrylic acid (AA), vinyl alcohol, dimethy-laminoethylmethacrylate (DMAEMA), styrene, maleic anhydride, acrylamide, methyl methacrylate, lauryl methacrylate (LM), a-olelins, methacrylamido-propyltrimethyl ammonium chloride (MAPTAC), vinyl caprolactam (VCL), and dimethylaminopropyl-methacrylamide (DMAPMA). 

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