FIELD: chemistry.
SUBSTANCE: invention relates to a method of producing 6-(N-methyl-N-phenyl)aminomethyl-hydrocortisone (11β,17α,21-trihydroxy-6-(N-methyl-N-phenyl)aminomethylpregn-4-ene-3,20-dione) or esters thereof of general formula I
,
in which R=COCF3 or H; R1=COCH3 or H, from hydrocortisone 21-acetate of formula II, a sequence of transformations, including protection 11β-hydroxyl group by esterification with a trifluoroacetic acid derivative in an aprotic solvent medium under conditions of basic catalysis using an effective amount of a catalyst to form 21-acetoxy-17α-hydroxy-11β-trifluoroacetoxypregn-4-ene-3,20-dione of formula III, enol-esterification Δ4-3-keto system of the obtained compound by the action of a trialkyl orthoformate in the presence of an acid catalyst to form a 3-alkoxyester Δ3,5-3-hydroxy derivative of general formula IV, condensing it with Mannich reagent, formed in situ from formaldehyde and N-methylaniline, in the presence of an acid catalyst and deprotection of 11β- and 21-hydroxyl groups by methods of chemical solvolysis completely (R=R1=H) or partially (R=H; R1=COCH3).
,
,
.
EFFECT: method has been developed for the preparation of compounds of formula I from hydrocortisone 21-acetate with the yield of the desired products of at least 85 %.
34 cl, 7 ex
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Authors
Dates
2018-08-06—Published
2017-12-29—Filed