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【结 构 式】 
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【分子编号】66713 【品名】2-Hydrazinopyrazine 【CA登记号】54608-52-5 |
【 分 子 式 】C4H6N4 【 分 子 量 】110.1186 【元素组成】C 43.63% H 5.49% N 50.88% |
与该中间体有关的原料药合成路线共 3 条
合成路线1
该中间体在本合成路线中的序号：(II)
| 【1】 Hansen KB, Balsells J. Dreher S et a1. 2005. First Generation Process for the Preparation of the DPP-IV Inhibitor Sitagliptin. Org Proc Rea.Dev.,9(5): 634～639. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 24075 | 2-chloropyrazine | 14508-49-7 | C4H3ClN2 | 详情 | 详情 |
| (II) | 66713 | 2-Hydrazinopyrazine | 54608-52-5 | C4H6N4 | 详情 | 详情 |
| (III) | 66714 | C8H4F6N4O2 | 详情 | 详情 | ||
| (IV) | 66715 | 3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine | C6H3F3N4 | 详情 | 详情 | |
| (V) | 66705 | 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride | 486460-21-3 | C6H7F3N4.HCl | 详情 | 详情 |
| (VI) | 66716 | methyl 3-oxo-4-(2,4,5-trifluorophenyl)butanoate | 769195-26-8 | C11H9F3O3 | 详情 | 详情 |
| (VII) | 66717 | (R)-3-hydroxy-4-(2,4,5-trifluorophenyl)butanoic acid | C10H9F3O3 | 详情 | 详情 | |
| (VIII) | 66718 | (R)-N-(benzyloxy)-3-hydroxy-4-(2,4,5-trifluorophenyl)butanamide | C17H16F3NO3 | 详情 | 详情 | |
| (IX) | 66719 | (R)-1-(benzyloxy)-4-(2,4,5-trifluorobenzyl)azetidin-2-one | C17H14F3NO2 | 详情 | 详情 | |
| (X) | 66720 | (R)-3-((benzyloxy)amino)-4-(2,4,5-trifluorophenyl)butanoic acid | C17H16F3NO3 | 详情 | 详情 | |
| (XI) | 66721 | (R)-3-((benzyloxy)amino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one | C23H21F6N5O2 | 详情 | 详情 | |
| (XII) | 66722 | (R)-3-amino-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one | 486460-32-6 | C16H15F6N5O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)
| 【1】 Kim D, Wang LP, Becoru M, et al. 2005. (2R)-4-Oxo-4-[3-(Trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}l-(2,4,5-trifluorophenyl)butan-2-amine:a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem, 48(1):141～151 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 66723 | 1-(bromomethyl)-2,4,5-trifluorobenzene | C7H4BrF3 | 详情 | 详情 | |
| (I) | 10296 | (R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine; (3R)-3-Isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether; (2R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine | 109838-85-9 | C9H16N2O2 | 详情 | 详情 |
| (III) | 66724 | (2S,5R)-2-isopropyl-3,6-dimethoxy-5-(2,4,5-trifluorobenzyl)-2,5-dihydropyrazine | C16H19F3N2O2 | 详情 | 详情 | |
| (IV) | 66725 | (R)-methyl 2-amino-3-(2,4,5-trifluorophenyl)propanoate | C10H10F3NO2 | 详情 | 详情 | |
| (V) | 66729 | (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(2,4,5-trifluorophenyl)propanoate | C15H18F3NO4 | 详情 | 详情 | |
| (VI) | 66728 | (R)-2-((tert-butoxycarbonyl)amino)-3-(2,4,5-trifluorophenyl)propanoic acid | C14H16F3NO4 | 详情 | 详情 | |
| (VII) | 66727 | (R)-tert-butyl (4-diazo-3-oxo-1-(2,4,5-trifluorophenyl)butan-2-yl)carbamate | C15H16F3N3O3 | 详情 | 详情 | |
| (VIII) | 66726 | (R)-3-((tert-butoxycarbonyl)amino)-4-(2,4,5-trifluorophenyl)butanoic acid | C15H18F3NO4 | 详情 | 详情 | |
| (IX) | 24075 | 2-chloropyrazine | 14508-49-7 | C4H3ClN2 | 详情 | 详情 |
| (X) | 66713 | 2-Hydrazinopyrazine | 54608-52-5 | C4H6N4 | 详情 | 详情 |
| (XI) | 66730 | 2,2,2-trifluoro-N'-(pyrazin-2-yl)acetohydrazide 2,2,2-trifluoroacetate | C6H5F3N4O.C2HF3O2 | 详情 | 详情 | |
| (XII) | 66715 | 3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine | C6H3F3N4 | 详情 | 详情 | |
| (XIII) | 66731 | 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine | C6H7F3N4 | 详情 | 详情 | |
| (XIV) | 66732 | (R)-tert-butyl (4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-yl)carbamate | C21H23F6N5O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号： (X)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