• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】35645

【品名】diethyl tartronate

【CA登记号】

【 分 子 式 】C7H12O5

【 分 子 量 】176.16928

【元素组成】C 47.73% H 6.87% O 45.41%

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:(V)

Addition of 4-tolylmagnesium bromide (II) to 2,3-pyridinedicarboxylic acid anhydride (I) afforded ketoacid (III). Subsequent condensation of (III) with diethyl bromomalonate (VII) in the presence of Et3N, followed by DBU-promoted cyclization produced the pyridine lactone (VI). In an alternative procedure, acid (III) was converted to acid chloride (IV) using SOCl2, and then condensed with diethyl hydroxymalonate (V) in the presence of NaH to give (VI). The tertiary alcohol group of (VI) was then dehydrated with HCl in AcOH to give (VIII). Acid chloride (IX), prepared by treatment of (VIII) with SOCl2, was coupled with 3,5-bis(trifluoromethyl)benzylamine (X) to furnish amide (XI). The tetrahydropyranyl-protected aminoalcohol (XIII) was obtained by reduction of nitrile (XII) with LiAlH4. Reaction of (XIII) with lactone (XI), followed by treatment with DBU, produced the 1,7-naphthyridine system (XIV). Acid-catalyzed deprotection of the tetrahydropyranyl group yielded alcohol (XV).

1 Tanaka, T.; Kawada, M.; Ishichi, Y.; Kamo, I.; Ishimaru, T.; Fujishima, A.; Ikeura, Y.; Natsugari, H.; Doi, T.; Kasahara, F.; Axially chiral 1,7-naphthyridine-6-carboxamide derivatives as orally active tachykinin NK1 receptor antagonists: Synthesis, antagonistic activity, and effects on bladder functions. J Med Chem 1999, 42, 19, 3982.
2 Natsugari, H.; Ishimaru, T.; Doi, T.; Ikeura, Y.; Kimura, C. (Takeda Chemical Industries, Ltd.); Cyclic cpds., their production and use as tachykinin receptor antagonists. CA 2172421; EP 0733632; JP 1997263585; JP 1997263587; US 5786352 .
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) 17247 furo[3,4-b]pyridine-5,7-dione; 2,3-Pyridinedicarboxylic anhydride 699-98-9 C7H3NO3 详情 详情
(II) 35657 bromo(4-methylphenyl)magnesium 4294-57-9 C7H7BrMg 详情 详情
(III) 35643 3-(4-methylbenzoyl)-2-pyridinecarboxylic acid C14H11NO3 详情 详情
(IV) 35644 3-(4-methylbenzoyl)-2-pyridinecarbonyl chloride C14H10ClNO2 详情 详情
(V) 35645 diethyl tartronate C7H12O5 详情 详情
(VI) 35646 diethyl 5-hydroxy-5-(4-methylphenyl)-8-oxo-5,8-dihydro-6H-pyrano[3,4-b]pyridine-6,6-dicarboxylate C21H21NO7 详情 详情
(VII) 35647 diethyl 2-bromomalonate 685-87-0 C7H11BrO4 详情 详情
(VIII) 35648 5-(4-methylphenyl)-8-oxo-8H-pyrano[3,4-b]pyridine-6-carboxylic acid C16H11NO4 详情 详情
(IX) 35649 5-(4-methylphenyl)-8-oxo-8H-pyrano[3,4-b]pyridine-6-carbonyl chloride C16H10ClNO3 详情 详情
(X) 35650 [3,5-bis(trifluoromethyl)phenyl]methanamine; 3,5-bis(trifluoromethyl)benzylamine 85068-29-7 C9H7F6N 详情 详情
(XI) 35651 N-[3,5-bis(trifluoromethyl)benzyl]-5-(4-methylphenyl)-8-oxo-8H-pyrano[3,4-b]pyridine-6-carboxamide C25H16F6N2O3 详情 详情
(XII) 35652 (3R)-3-methyl-4-(tetrahydro-2H-pyran-2-yloxy)butanenitrile C10H17NO2 详情 详情
(XIII) 35653 (3R)-3-methyl-4-(tetrahydro-2H-pyran-2-yloxy)butylamine; (3R)-3-methyl-4-(tetrahydro-2H-pyran-2-yloxy)-1-butanamine C10H21NO2 详情 详情
(XIV) 35654 N-[3,5-bis(trifluoromethyl)benzyl]-5-(4-methylphenyl)-7-[(3R)-3-methyl-4-(tetrahydro-2H-pyran-2-yloxy)butyl]-8-oxo-7,8-dihydro[1,7]naphthyridine-6-carboxamide C35H35F6N3O4 详情 详情
(XV) 35655 N-[3,5-bis(trifluoromethyl)benzyl]-7-[(3R)-4-hydroxy-3-methylbutyl]-5-(4-methylphenyl)-8-oxo-7,8-dihydro[1,7]naphthyridine-6-carboxamide C30H27F6N3O3 详情 详情
Extended Information