【结 构 式】 |
【药物名称】PJ-34 【化学名称】2-(Dimethylamino)-N-(6-oxo-5,6-dihydrophenanthridin-2-yl)acetamide hydrochloride 【CA登记号】 【 分 子 式 】C17H18ClN3O2 【 分 子 量 】331.80491 |
【开发单位】Inotek (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Cerebrovascular Diseases, Treatment of, ENDOCRINE DRUGS, NEUROLOGIC DRUGS, Stroke, Treatment of, Treatment of Diabetic Complications, Treatment of Septic Shock, NAD+ ADP-Ribosyltransferase (poly(ADP-ribose)polymerase; PARP) Inhibitors |
合成路线1
Treatment of 9-fluorenone (I) with H2SO4 and sodium azide furnishes phenanthridinone derivative (II), which is then nitrated by means of HNO3 in HOAc to provide compound (III). Reduction of the nitro moiety of (III) by means of Fe and NH4Cl in DMF affords amino derivative (IV), which is then acylated with chloroacetyl chloride (V) in ethyl acetate in the presence of NaHCO3 or pyridine/DMF to yield chloroacetamide derivative (VI). Finally, the target compound can be obtained by condensation of (VI) with dimethyl amine (VII) in DMF/MeOH followed by treatment with HCl/Et2O in MeOH. Alternatively, the desired product can be synthesized as follows: Treatment of 2-amino-9-fluorenone (VIII) with chloroacetyl chloride (V) in AcOEt and NaHCO3 gives chloroacetamide (IX), which is then subjected to reaction with dimethyl amine (VII) in DMF/MeOH to provide dimethylacetamide (X). Reaction of (X) with H2SO4 and sodium azide, followed by treatment with HCl/Et2O in MeOH, affords a mixture of regioisomers from which the desired compound is isolated.
【1】 Southan, G.; Jagtap, P.; Szabo, C.; Salzman, A. (Inotek Corporation); Substd. phenanthridinones and methods of use thereof. US 6277990 . |
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) | 48902 | 9-Fluorenone; fluorenone | 486-25-9 | C13H8O | 详情 | 详情 |
(II) | 48903 | 6(5H)-Phenanthridinone; Phenanthridinone | 1015-89-0 | C13H9NO | 详情 | 详情 |
(III) | 48904 | 2-Nitro-6(5H)-phenanthridinone | C13H8N2O3 | 详情 | 详情 | |
(IV) | 48905 | 2-amino-6(5H)-phenanthridinone | C13H10N2O | 详情 | 详情 | |
(V) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
(VI) | 48906 | 2-chloro-N-(6-oxo-5,6-dihydro-2-phenanthridinyl)acetamide | C15H11ClN2O2 | 详情 | 详情 | |
(VII) | 19443 | N-methylmethanamine; N,N-dimethylamine | 124-40-3 | C2H7N | 详情 | 详情 |
(VIII) | 48907 | 3-Amino-9-fluorenone | C13H9NO | 详情 | 详情 | |
(IX) | 48908 | 2-chloro-N-(9-oxo-9H-fluoren-3-yl)acetamide | C15H10ClNO2 | 详情 | 详情 | |
(X) | 48909 | 2-(dimethylamino)-N-(9-oxo-9H-fluoren-3-yl)acetamide | C17H16N2O2 | 详情 | 详情 |