Hydrochloric Acid → HCID 67924524, compound

A solution of 538 mg (2.29 mmol) of (R)-α-[[(1,1-dimethylethyl)amino]methyl]tetrazolo[1,5-a]- pyridine-6-methanol in 15 ml of methanol was treated with 0.19 ml (2.29 mmol) of concentrated hydrochloric acid and 1.03 g (4.58 mmol) of SnCl2 ·2H2O. The reaction mixture was heated at reflux for one hour at which point tlc (silica gel) indicated completion. The mixture was reduced in volume under reduced pressure and then diluted with methylene chloride. The organic solution was washed with 15 ml of 2.5 N NaOH solution. The aqueous layer was back washed with a 20% methanolic methylene chloride solution until all product had been recovered. The combined organic layers were washed with saturated sodium chloride solution (2X), dried with anhydrous magnesium sulfate, and concentrated to dryness. The crude product was chromatographed on silica gel with 80:20:2 methylene chloride:methanol:concentrated aqueous ammonia as eluent to five 434 mg of pure product. To a solution of this free base (2.07 mmol) in 3 ml of absolute ethanol, a solution of 506 mg (4.36 mmol) of maleic acid in 5 ml of absolute ethanol was added slowly. The heterogeneous mixture was permitted to stir for an additional hour. The precipitate was collected by filtration and washed with ethanol-ether and then ether to give 690 mg of salt. The filtrate was diluted with ether to afford additional solid which was collected and rinsed with ethanol-ether and ether to afford 110 mg of product (total yield, 88%). A sample was recrystallized from ethanol, m.p. 167°-68° C. (dec.); [α]25D=-35.0 (MeOH); Analysis: Calc'd. for C11H19N3O·2C4H4O4 :

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for one hour at which point tlc (silica gel)
3. washThe organic solution was washed with 15 ml of 2.5 N NaOH solution
4. washThe aqueous layer was back washed with a 20% methanolic methylene chloride solution until all product
5. customhad been recovered
6. washThe combined organic layers were washed with saturated sodium chloride solution (2X)
7. dry with materialdried with anhydrous magnesium sulfate
8. concentrationconcentrated to dryness
9. customThe crude product was chromatographed on silica gel with 80:20:2 methylene chloride
10. filtrationThe precipitate was collected by filtration
11. washwashed with ethanol-ether

ORD record

ord-6d87611fbc114c55be6dc65b5f2a00ab

Source dataset

uspto-grants-1991_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05019578