LX-4211 synthesis

6synthesis methods

Product Name:LX-4211
CAS Number:1018899-04-1
Molecular formula:C21H25ClO5S
Molecular Weight:424.94

Sotagliflozin is a dual SGLT-1/SGLT-2 inhibitor which is currently under development by Lexicon Pharmaceuticals (phase III). It follows a similar strategy to ertugliflozin, i.e. aryl addition on an acyclic precursor. The synthesis starts from L-xylose 53, and the aryl moiety (same aryl moiety as for dapagliflozin) is introduced on an amide derivative (morpholine amide 54) via Grignard addition. A subsequent transformation leads to the sotagliflozin (Scheme 10). The overall yield of the synthesis is around 30%.

Sotagliflozin synthesis

β-L-Xylopyranoside, Methyl 5-C-[4-chloro-3-[(4-ethoxyphenyl)Methyl]phenyl]-1-thio-, 2,3,4-triacetate,(5S)-

1018899-03-0
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1018899-04-1
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Yield:1018899-04-1 99.7%

Reaction Conditions:

with methanol;sodium methylate in toluene at 113; under 13501.4 Torr; for 0.00555556 h;Temperature;Pressure;

Steps:

1; 2; 3 Synthesis of sotagliflozin in toluene
Sotagliflozin was synthetized in an intensified reactor at 113°C under a pressure of 8 bar.The reactor was fed with the solution of compound (A) in 10 Volumes of toluene with a flow of 1194.6 g/h and the methanolic solution of MeONa (0.6 equivalent of MeONa and 15 equivalents of MeOH) with a flow of 114.6 g/h, which were preheated at 113°C.The time of residence in the reactor was 20 seconds.The system was maintained at a pressure of 8 bar.Sotagliflozin was synthetized with a yield of 99.7%.Aqueous washing, dehydration, crystallization, filtration, washing, drying were performed according to example 2.An XRPD (X-ray diffraction) analysis confirmed that Form II of sotagliflozin was obtained.

References:

LEXICON PHARMACEUTICALS, INC. WO2021/19507, 2021, A1 Location in patent:Page/Page column 9-12

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67-63-0 Synthesis