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【结 构 式】

【分子编号】67858

【品名】(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

【CA登记号】 

【 分 子 式 】C13H7F6N3O2

【 分 子 量 】351.208

【元素组成】C 44.46% H 2.01% F 32.46% N 11.96% O 9.11%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

Reaction of 3,4-bis(trifluoromethyl)benzonitrile (I) with NaSH by means of MgCl2 in DMF gives 3,5-bis(trifluoromethyl)benzothioamide (II), which by cyclization with hydrazine hydrate (III) and HCOOH in DMF provides 3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazole (IV). Esterification of propiolic acid (V) with i-PrOH in the presence of BF3·Et2O at 90 °C affords isopropyl propiolate (VI), which is iodinated with NaI in AcOH at 110 °C to obtain isopropyl (Z)-3-iodoacrylate (VII). Condensation of triazole derivative (IV) with isopropyl (Z)-3-iodoacrylate (VII) in the presence of DABCO in DMF yields intermediate (VIII), which is subjected to ester hydrolysis with LiOH in H2O/THF to provide the corresponding carboxylic acid (IX). Finally, acid (IX) is coupled with 2-hydrazinopyrazine (X) in the presence of T3P and DIEA in CH2Cl2/EtOAc .

1 McCauley, D., Shacham, S., Sandanayaka, V.P., Shechter, S. (Karyopharma Therapeutics, Inc.). Hydrazide containing nuclear transporter modulators and uses thereof. EP 2736887, JP 2014521652, KR 2014066179, US 2014235653, WO 2013019548.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(X) 66713 2-Hydrazinopyrazine 54608-52-5 C4H6N4 详情 详情
(I) 67851 3,5-bis(trifluoromethyl)benzonitrile 27126-93-8 C9H3F6N 详情 详情
(II) 67852 3,5-bis(trifluoromethyl)benzothioamide 317319-15-6 C9H5F6NS 详情 详情
(III) 67853 hydrazine hydrate 7803-57-8 H4N2.H2O 详情 详情
(IV) 67854 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole   C10H5F6N3 详情 详情
(V) 41770 propiolic acid 471-25-0 C3H2O2 详情 详情
(VI) 67855 isopropyl propiolate   C6H8O2 详情 详情
(VII) 67857 isopropyl (Z)-3-iodoacrylate   C6H9IO2 详情 详情
(VIII) 67856 (Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate   C16H13F6N3O2 详情 详情
(IX) 67858 (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid   C13H7F6N3O2 详情 详情
Extended Information