(dimethyl)[10H-pyrido[3,2-b][1,4]benzothiazine-10-propyl]ammonium chloride synthesis

Yield: 96%

Reaction Conditions:

Stage #1:3-dimethylaminopropionic acid with sodium tetrahydroborate in toluene at 0 - 5;
Stage #2:1-azaphenothiazine with sodium tetrahydroborate in toluene at 25 - 75; for 6 h;
Stage #3: with hydrogenchloride in water;isopropyl alcohol

Steps:

General procedure for synthesis of compounds 3a-3ao
General procedure: 4 mmol of carboxylic acid in toluene (5 vol) was added with sodium borohydride (2.5 mmol) in portions at 0-5°C. To the mixture was added EnCat Ni 2.5 %. Gradually raise the temperature to 25-30 °C. To the mixture was added 1 mmol secondary amine. Raise the temperature to 80 °C. To the reaction mixture was added 1.5 mmol of sodiumborohydride in portions. The progress of the reaction was monitored by TLC. After the completion of reaction, reaction mixture was quenched with 1N HCl to pH 7 to 8 and separated organic solution washed with water. Solvent was distilled out under reduce pressure at 50 °C. The product was isolated by crystallisation in isopropyl alcohol and conc. Hydrochloric acid followed by filtration and drying to yield (90-99 %) solid hydrochloride salt as product.

References:

Quadri, Syed Aziz Imam;Das, Tonmoy C.;Jadhav, Shivaji;Farooqui, Mazahar [Synthetic Communications,2018,vol. 48,# 3,p. 267 - 277] Location in patent:supporting information