5-methyl-4,5-dihydro- -chloride

If the quaternary nitrogen is a member of a ring, the ring is cleaved. 3-Benzyl-2-phenyl-A, A -dimethylpyrrolidinium chloride was cleaved by hydrogenation over Raney nickel at 20-25° almost quantitatively to 2-benzyl-4-dimethylamino-l-phenylbutane [722]. Reduction of methylpyridinium iodide (and its methyl homologs) with sodium aluminum hydride gave 24-89% yields of 5-methylamino-l,3-pentadiene (and its methyl homologs) in addition to A -methyl dihydro- and tetrahydropyridine [448]. 

Phenazarsinium 10-Amino-10-methyl-5,10-dihydro- (Chlorid) XIII/8, 366f. 

Gemischte Benzoesaure-anhydride werden aus 2-Benzoylthio-l-methyl-pyridinium-chlorid(I) und carbonsauren Salzen erhalten. Hierzu wird 1-Methyl-2-thiono-l,2-dihydro-pyridin mit Benzoylchlorid in Chloroform/Wasser mit dem betreffenden Carboxylat oder mit der Carbonsaure in Gegenwart einer aquivalenten Menge Natronlauge umgesetzt92 ... 

Phthalazine (37) with chloromethyl trimethylsilylmethyl sulfide gave 2-[(tri-methylsilylmethylthio)methyl]phthalazinium chloride (38) (reactants, MeCN, 60°C, 1 h 96%) and thence l,10b-dihydro-3//-thiazolo[4,3-fl]phthalazine (39) (CsF, MeCN, 20°C, 48 h 92%) the reaction may be done as a one-pot procedure without isolation of the intermediate. 

The syntiiesis of DPP-4 inhibitor, Saxagliptin 1 (Figure 4.21) required key intermediate (5S)-5-aminocarbonyl-4,5-dihydro-lH-pyrrole-l-carboxylic acid,l-(l,l-dimethyl ethyl)-ester 76 [22-24]. Direct chemical ammonolysis resulted in unacceptable levels of amide racemization and side-product formation. Milder, two-step hydrolysis-condensation protocols using coupling agents such as 4-(4,6-dimetiioxy-l,3,5-triazin-2-yl)-4-methyl-morpholinium chloride (DMT-MM) were compromised by reduced overall yields [103]. 

Apart from the syntheses already quoted as of possible biological interest, mention must be made of a series which are primarily of chemical interest. Kermack, Perkin and Rob mson prepared norharman, i.e., /S-carboline (VII) by warming A-methylindole-2-carboxyacetalylamide (XVIII) with alcoholic hydrogen chloride, thereby converting it into 2-keto-l-methyl-2 3-dihydro-/S-carboline (XIX), which on distillation... 

It is interesting to note that the 7,12-dihydro-2-methyl-6H-indolo[2,3-n] quinolizinium chloride (216) (R = acetal) can be deprotonated to give the orange-yellow zwitterion 217, whereas the vinylog amide 218 is formed when R = COMe (Scheme 71). This substitution pattern gives rise to the... 

The papaver alkaloid Narcotoline (265) can be converted into the yellow colored Cotarnoline (267) on hydrolysis which adopts a zwitterionic ground state (56MI1, 57MI1) (Scheme 87). The corresponding dihydro derivative was also identified in nature. The UV spectrum of the zwitterionic Tarkonine (268), which forms red crystals from acetone, is shifted bathochromically in comparison to the chloride. Tarkonine is a very weak base (pA b = 9.58), which is well in accord with the formation of an inner salt, and Cotarnoline (267) is a stronger base than Tarkonine (268) (pA b = 9.15). The pK values are larger than 13 (66MI3). The methylated derivative of Narcotoline is Narcotine (266). 

Preparation of 4-aza-S-(N-methyl-4-piperidyll-10,11-dihydro-SH-dibenzo[a,d]cycloheptene-S-ol Add 17.4 g of N-methyl-4-chloropiperidine to a stirred mixture containing 3.2 g of magnesium, 20 ml of anhydrous tetrahydrofuran, 1 ml of ethyl bromide and a crystal of iodine. Reflux for two hours, cool to 30°-35°C and add a solution of 13 g of 4-aza-10,11 -dihydro-5H-dibenzo[a,d] cycloheptene-5-one in 25 ml of tetrahydrofuran. Stir for five hours, remove the solvent by distillation in vacuo and add 250 ml of ether. Add 100 ml of 10% ammonium chloride solution and extract the mixture with chloroform. Concentrate the chloroform solution to a residue and recrystallize from isopropyl ether obtaining 20 g of the carbinol,... 

A solution of 60 g of chromic anhydride in 40 ml of water was added dropwise to a suspension of 60 g of 2-aminomethyl-1 -methyl-5-chloro-3-(o-fluorophenyl)-indole hydrochloride in 600 ml of acetic acid. The mixture was stirred at room temperature overnight. To the reaction mixture was added 1.1 liters of ether and 1 liter of water and then 800 ml of 28% ammonium hydroxide, in small portions. The ethereal layer separated, washed with water, dried, and concentrated under reduced pressure. The residue (51.8 g) was dissolved in 100 ml of ethanol, and 100 ml of 20% ethanollc hydrogen chloride was added to the solution and the mixture was cooled. The precipitate was collected by filtration to yield 46.5 g of 1 -methyl-7-chloro-5-(o-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepine-2-one hydrochloride, melt-... 

Dihydro-17a-ethynyl-18-homo-oestradiol 3-methyl ether Hydrogen chloride... 

C) Preparation of 2-Methyl-3-(2,2,2-Trifluoroethyl)Thiomethyl-6-Chloro-7-Sulfamyl-3,4-Dihydro-1,2,4-Benzothiadiazine-1,1-Dioxide To 4.6 g (0.015 mol) of 4-amino-2-chloro-5-(methylsulfamyl)benzenesulfonamide in 30 ml of the dimethyl ether of ethylene glycol is added 4.08 g (0.02 mol) of 2,2,2-trifluoroethylmercaptoacetaldehyde dimethylacetal followed by 1 ml of ethyl acetate saturated with hydrogen chloride gas. The resulting solution is refluxed for 1.5 hours, cooled and then slowly added to cold water dropwise with stirring. The crude product is filtered, dried and recrystallized from isopropanol (3.2 g), MP 202° to 202.5°C. A second recrystallization from isopropanol raised the MP to 202°... 

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