On December 17, 2009, Knust, Henner; Nettekoven, Matthias; Pinard, Emmanuel; Roche, Olivier; Rogers-Evans, Mark published a patent.Quality Control of (6-(Trifluoromethyl)pyridin-3-yl)methanol The title of the patent was Preparation of heteroaromatic monoamides as orexin receptor antagonists. And the patent contained the following:
The present invention is concerned with novel amides of formula [I; (i) Ar1 = heteroaryl, Ar2 = Ph, and Ar = Ph or heteroaryl; or (ii) Ar1 = Ph, Ar2 = heteroaryl, and Ar = Ph or heteroaryl; or (iii) Ar1 = heteroaryl, Ar2 = heteroaryl, and Ar = Ph or heteroaryl; R1 = H, halogen, lower alkyl, halo-lower alkyl, lower alkoxy; R2 = H, halogen, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy; R3 = H, halogen, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cycloalkyl-lower alkyl, C(O)O-lower alkyl, C(O)NH-lower alkyl, (CH2)m-O-lower alkyl, lower alkoxy, etc.; or where Ar2 = Ph and o = 2, R3 optionally is R3 and R3′ which together with the corresponding carbon atoms to which they are attached form a non aromatic ring containing the groups (CH2)4, (CH2)3, CH2S(O)2CH2, N(Me)C(O)N(Me), (CH2)2O, O(CH2)2O, O(CH2)2CH(OH), O(CH2)2, O(CH2)3, etc.; R4, R5 = H, hydroxy, lower alkyl, lower alkoxy, CH2NH2, O-C(O)lower alkyl, or NRR’; or R4 and R5 together are :O; R, R’ = H, S(O)2-lower alkyl, cycloalkyl, (CH2)mOH, (CH2)mO-lower alkyl, C(O)CH(NH2)Ph, or oxetan-3-yl optionally substituted by CH2NH2, or NRR’ together form a heterocycloalkyl ring, optionally containing in addition to the N atom a further heteroatom, selected from the group consisting of N, S and O; n, o, p = 1-3; m = 0-2] or pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixtures thereof. These compounds are orexin receptor antagonists that may be useful in the treatment of disorders, in which orexin pathways are involved, e.g. in arousal, sleep/wakefulness, appetite regulation and their roles in anxiety and stress response, etc. The drugs (or compounds) targeting orexin system will have beneficial therapeutic effects for the treatments of diseases like sleep disorders including sleep apnea, narcolepsy, insomnia, parasomnia, jet lag syndrome, circadian rhythms disorder, restless leg syndrome, psychiatric, neurol. and neurodegenerative disorders, etc. Thus, 500 mg (3,4-dimethylphenyl)[2-(6-trifluoromethylpyridin-3-yl)ethyl]amine > was condensed with 300 mg (4-fluorophenyl)oxoacetic acid using in CH2Cl2 with stirring for 12 h at ambient temperature to give, after workup and silica gel chromatog., N-(3,4-dimethylphenyl)-2-(4-fluorophenyl)-2-oxo-N-[2-(6-trifluoromethylpyridin-3-yl)ethyl]acetamide (527 mg, 70%) (II) as a light yellow. II (515 mg) was reduced by 88 mg NaBH4 in MeOH with stirring for 12 h at ambient temperature to give, after workup and silica gel chromatog., N-(3,4-dimethylphenyl)-2-(4-fluorophenyl)-2-hydroxy-N-[2-(6-trifluoromethylpyridin-3-yl)ethyl]acetamide (501 mg, 97%) which was separated by chromatog. on a chiral column to give (S)-N-(3,4-dimethylphenyl)-2-(4-fluorophenyl)-2-hydroxy-N-[2-(6-trifluoromethylpyridin-3-yl)ethyl]ethanamide (III). III showed inhibited orexin receptor-2 receptor (OX2R) with Kb of 0.0005 μM in an intracellular Ca2+ mobilization assay in Chinese hamster ovary mutant cell line stably expressing human OX2R. The experimental process involved the reaction of (6-(Trifluoromethyl)pyridin-3-yl)methanol(cas: 386704-04-7).Quality Control of (6-(Trifluoromethyl)pyridin-3-yl)methanol
The Article related to phenylpyridinylethylacetamide preparation orexin receptor antagonist, sleep disorder treatment phenylpyridinylethylacetamide preparation, heteroaromatic monoamide preparation orexin receptor antagonist, psychiatric neurol neurodegenerative disorder treatment heteroaromatic monoamide preparation and other aspects.Quality Control of (6-(Trifluoromethyl)pyridin-3-yl)methanol
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