On June 26, 2014, Kobayashi, Kaori; Suzuki, Tamotsu; Okuzumi, Tatsuya published a patent.Synthetic Route of 386704-04-7 The title of the patent was Preparation of N-arylsulfonyl amino acid amide derivatives as transient receptor potential ankyrin 1 (TRPA1) antagonists and medicine containing them. And the patent contained the following:
The title compounds represented by formula [I; Ar = each (un)substituted C6-10 aryl or C1-9 heteroaryl; Y = C(Ry1)(Ry2) or a single bond; Z = C(Rz1)(Rz2), O, S, or a single bond; n, m = 0 or 1 and n+m≤1; ring A = (un)substituted phenylene or 5- or 6-membered divalent heteroaromatic ring; ring B = (un)substituted C6-10 aryl or C1-9 heteroaryl; R1 = H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo-C1-6 alkyl, C3-6 cycloalkyl, or C3-6 cycloalkyl-C1-6 alkyl; R2, R3 = H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl; R4-R8, Ry1, Ry2, Rz1, Rz2 = H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo-C1-6 alkyl, C1-6 alkoxy, HO, halo-C1-6 alkoxy, NH2, C1-6 alkyl, mono- or disubstituted amino, or halo; each adjacent R4-R8, Ry1, Ry2, Rz1, or Rz2 together forms a double bond and/or ring; or R5 and R6, R7 and R8, Ry1 and Ry2, or Rz1 and Rz2 on the same carbon atom together form a ring; Rx1, Rx2, Rx2, Rx3, Rx4 = H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxy-C1-6 alkyl, amino-C1-6 alkyl, or mono- or di(C1-6 alkyl)amino-C1-6 alkyl; or Rx1 and Rx2 or Rx3 and Rx4 on the same carbon together form a ring] or pharmaceutically acceptable salts thereof are prepared These compounds have transient receptor potential ankyrin 1 (TRPA1) antagonistic activity and are useful for the prevention or treatment of diseases associated with a TRPA1 antagonist and TRPA1, in particular pain-related diseases, inflammatory diseases, digestive tract diseases, pulmonary diseases, bladder diseases, skin diseases, or nerve diseases, more specifically chronic pain, acute pain, asthma, chronic obstructive pulmonary disease, functional gastrointestinal disorders, reflux esophagitis, inflammatory bowel disease, or pruritus. Thus, L-proline was condensed with 5-chlorothiophene-2-sulfonyl chloride in the presence of NaOH in aqueous THF solution at room temperature overnight to give 97% (2S)-1-(5-chlorothiophene-2-sulfonyl)pyrrolidine-2-carboxylic acid which was condensed with 4-(aminomethyl)phenol using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1-hydroxy-7-azabenzotriazole (HOAt) in the presence of Et3N in CH2Cl2 at room temperature for a few hours to give 72% (2S)-1-(5-chlorothiophene-2-sulfonyl)-N-[(4-hydroxyphenyl)methyl]pyrrolidine-2-carboxamide (II; R = H). II (R = H) was condensed with phenylboronic acid in the presence of supper acetate, Et3N, and mol. sieve 4Å in CH2Cl2 at room temperature for a few hours to give II (R = Ph). II (R = Ph) and (2S)-1-(3-thienylsulfonyl)-N-[[3-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]methyl]pyrrolidine-2-carboxamide (III) inhibited the allyl isothiocyanate-stimulated increase in cellular calcium concentration in human fetus kidney cell-derived 293T cells expressing human TRPA1 with IC50 of 0.22 and 0.0085 μM, resp. The experimental process involved the reaction of (6-(Trifluoromethyl)pyridin-3-yl)methanol(cas: 386704-04-7).Synthetic Route of 386704-04-7
The Article related to arylsulfonylproline amide preparation transient receptor potential ankyrin 1 antagonist, arylsulfonyl amino acid amide preparation trpa1 antagonist, pain inflammatory disease prevention treatment, digestive tract disease prevention treatment, pulmonary disease prevention treatment, bladder disease skin disease prevention treatment and other aspects.Synthetic Route of 386704-04-7
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