New downstream synthetic route of 13745-86-3

Synthetic Route of 13745-86-3, These common heterocyclic compound, 13745-86-3, name is 11-Chlorodibenzo[b,f][1,4]thiazepine, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Example 1 Preparation of 1 l-piperazin-l-yldibenzor&,/iri,4~lthiazepineInto a 1000 mL round-bottom flask equipped with a magnetic stirring bar and reflux condenser with a nitrogen inlet was charged with 25.0 grams (g) (0.110 mole) of dibenzo[b,fj[l,4]thiazepine-l l(10-H)-one (made by the method disclosed by J. Schmutz et al. HeIv. Chim. Acta., 48: 336 (1965)), as a dry solid, followed by 310 mL POCl3 and 3 mL of N,N-dimethylaniline. The reaction mixture was heated at reflux (106 degrees C) for 6 hours giving a clear orange solution. The reaction was then cooled to room temperature, and POCl3 removed on the rotary evaporator leaving an orange oil. This residue was partitioned between ice -water (500 mL) and ethyl acetate (800 mL). The layers were separated and the aqueous phase extracted with ethyl acetate (3 X 200 mL). The combined ethyl acetate extracts were dried over MgSO4 , filtered, and then stripped down on the rotary evaporator, leaving the crude imino chloride as a light yellow solid (26.26g, 97% yield). The structure was confirmed by NMR and Mass Spectrum (300 MHz, CDCl3; ES+, M+l = 246.7). Crude imino chloride (27.35 g, 0.111 mole) was added to 1000 mL o-xylene in a 2000 mL round-bottom flask equipped with a magnetic stir bar and a reflux condenser with nitrogen inlet. To this solution was added commercially available piperazine (47.95g, 0.557 mole) in one portion as a dry solid at room temperature. The mixture was stirred until nearly all the piperazine dissolved. EPO Then the reaction mixture was heated at reflux (142 degrees C) for 40 hours (out of convenience). The reaction was then allowed to cool to room temperature, and an aliquot was partitioned between IN NaOH / CH2Cl2. The organic phase was checked by TLC (silica gel, CH2Cl2 / Methanol 90:10, iodoplatinate visualized) and showed clean conversion to one major product (Rf = 0.45). A drop of the reaction solution was diluted with CH3CN to prepare a sample for LC / MS analysis, which confirmed the presence of the desired product (M+l = 296.4). The reaction mixture was stripped down on the rotary evaporator under high vacuum to remove the xylene. The residue was partitioned between IN NaOH (400 mL) and CH2Cl2 (200 mL). The layers were separated, and the aqueous phase further extracted with CH2Cl2 (3 X 200 mL). The combined CH2Cl2 extracts were washed with brine (200 mL), then dried over MgSO4, filtered, and stripped down on the rotary evaporator to give the crude title compound as a yellow gum (35.3 g). The crude free base was purified by flash column chromatography over silica gel (600 g) eluting with a gradient of 0 to 20% Methanol in CH2Cl2. Fractions containing the pure desired product were combined and stripped down on the rotary evaporator, to afford the purified free base as a light yellow foam (25.67g, 78% yield).

The synthetic route of 13745-86-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WO2006/73360; (2006); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics