Dibenzo[c,f][1,2]thiazepin-11(6H)-one, 3-chloro-6-methyl-, 5,5-dioxide

Pd2dba (20.6 mg, 0.0225 mmol), XPhos (21.5 mg, 0.0450 mmol), and K2CO3 were combined in anhydrous DMF (3.0 mL) and the dark-brown mixture was stirred at room temperature for 5 min. Ketone 3d (462 mg, 1.50 mmol) and (trimethylsilyl) acetylene (505 pL, 2.25 mmol) were then added and the mixture was heated to 110 °C for 3 h. The mixture was then cooled to room temperature, diluted with water (20 mL) , and extracted with Et20 (3 x 30 mL) . The combined organics were washed with water (2 x 20 mL) and brine (20 mL) , dried over a2SC , and concentrated to give an orange-brown solid. This material was purified by column chromatography (6:4 hexanes : CH2CI2, 3 column volumes ' 1:1 hexanes : CH2CI2, 5 column volumes) to provide pure ketone 3g as pale-yellow foam, which, on addition of a little Et20, formed powdery, pale-yellow crystals (553 mg, 81percent) . 1H NMR (400 MHz, CDCI3) delta 8.31 (dd, J = 8.1, 1.7 Hz, 1H) , 8.01 (d, J = 1.6 Hz, 1H) , 7.91 (d, J = 8.0 Hz, 1H) , 7.75 (dd, J = 8.0, 1.6 Hz, 1H) , 7.68 - 7.61 (m, 1H) , 7.38 (ddd, J = 8.2, 7.3, 1.2 Hz, 1H) , 7.34 (dd, J = 8.1, 1.1 Hz, 1H) , 3.36 (s, 3H) , 1.21 - 1.10 (m, 21H) ; 13C NMR (101 MHz, CDCI3) delta 190.1, 141.6, 137.3, 136.4, 135.3, 135.0, 132.2, 131.8, 131.2, 128.6, 128.1, 126.3, 124.8, 104.3, 97.5, 39.2, 18.8, 11.4.339KG intermediate B, adding the concentrated sulfuric acid 780KG reactor, heated to 40 degrees, Stir, continue to heat up to 65 degrees, the reaction 5 hours. High performance liquid phase monitoring of intermediate B conversion is complete, Cooling to 20 degrees, the reaction solution slowly transferred to the 1000KG ice water inside the reactor, Outside the ice brine cooling, temperature control is not high 50 degrees. After the transfer is completed, the temperature is reduced to 8 degrees crystallization for 3 hours, Centrifuge white solid wet weight 389KG, HPLC: 98.8percentThe obtained solid was transferred to a reaction kettle, and the inside of the kettle was preliminarily loaded into methanol 1400KG. After heating and dissolving, Cooling to 6 degrees crystallization 6 hours, centrifugal fine 60 degrees drying total finished product 296KG, yield 96.4percentHPLC: 99.9percent.Refined mother liquor for distillation and recovery of methanol recycling;The reaction mother liquor was adjusted to pH 7.0 via sodium hydroxide and concentrated to precipitate the sodium sulfate by-product.The 32.6g (0.1mol) 2 - (N-methyl-N-phenyl-amine sulfonyl) - 4-chloro-benzoic acid is added to the 326g methylene chloride, by adding 17.8g (0.15mol) thionyl chloride and 32.6g mixed solution of methylene chloride, 40 C -44 C heating to reflux, the reaction 4 hours, after the reaction, cooling to room temperature, then adding 28.4g (0.15mol) titanium tetrachloride and 32.6g mixed solution of methylene chloride, 40 C -44 C heating to reflux, the reaction 3 hour; after the reaction by adding the reaction liquid 326g hydrolyze in water, layered, the layer using 97.8g dichloromethane extraction, combined with the organic layer, to concentrated to dry 32.6g methanol refining, filtering, drying to obtain tianeptine intermediate 3-chloro-6-methyl-dibenzo [c, f] [1, 2] parathiazine -11 (6H)-one -5, 5-dioxide 29.2g, molar yield 94.9%, liquid phase purity> 99.6%.Compound 4 (32.6 g, 0.1 mol) was dissolved in 250 mL of xylene in a 500 mL three-necked flask.32 g of perfluorosulfonic acid resin catalyst was added. Heating to reflux and reacting for 10 hours, Cool to room temperature, filter, solid wash with xylene, sealed package directly next time.The filtrate was recovered under reduced pressure, and the crude material was crystallised from ethanol to give the product 24.6 g.The yield was 80%.

A metabolite of Tianeptine, an antidepressant. A triazine derivative as potent modulators of multidrug resistance.

Molecular Weight:307.8
XLogP3:2.8
Hydrogen Bond Acceptor Count:4
Exact Mass:307.0069920
Monoisotopic Mass:307.0069920
Topological Polar Surface Area:62.8
Heavy Atom Count:20
Complexity:501
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes