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【结 构 式】

【分子编号】44863

【品名】 

【CA登记号】

【 分 子 式 】C17H12N6O

【 分 子 量 】316.32212

【元素组成】C 64.55% H 3.82% N 26.57% O 5.06%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XIV)

Treatment of carboxylic acid (I) with refluxing cyclohexanone (II) and H2SO4 affords derivative (III), which is then condensed with propargyl bromide (IV) by means of NaH in DMF to yield propargyl ether (V). Treatment of (V) with Et3N in toluene followed by condensation with 4-cloro-iodobenzene (VI) by means of PdCl2, PPh3 and CuI provides propinyloxy derivative (VII), which is then converted into propenyloxy derivative (VIII) by hydrogenation over Pd/ BaSO4 in pyridine. Opening of the lactone ring of (VIII) by means of NaH in MeOH and THF affords methyl ester (IX), which is then condensed with benzoyl chloride (X) by means of DMAP and Et3N in CH2Cl2 to give benzoate (XI). Treatment of (XI) with Et2Zn and chloroiodomethane in dichloroethane (or alternatively in CH2Cl2 or THF) followed by recrystallization from isopropanol furnishes cyclopropane derivative (XII), which is then hydrolyzed by treatment with NaOH in dioxane to yield alcohol (XIII). Finally, (XIII) is condensed with intermediate (XIV) by means of NaH in DMF and then deprotected by treatment with HCl in dioxane to afford the target compound.

1 Hemmerle, H.; Schindler, P.; Herling, A. (Aventis SA); Derivs. of substd. cyclohexane, their process of preparation and their application for the treatment of diseases. EP 0587088; JP 1994211736; US 5463062 .
2 Hemmerle, H.; Schubert, G.; Burger, H.-J.; Herling, A.; Efendic, S. (Aventis SA); Cyclohexane derivs., processes for their preparation and their use as glucose-6-phosphatase inhibitors. CA 2149007; CA 4416433; EP 0682024; JP 1995330767; US 5739147 .
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) 44864 Quinic acid; 1,3,4,5-tetrahydroxycyclohexanecarboxylic acid C7H12O6 详情 详情
(II) 11059 Cyclohexanone 108-94-1 C6H10O 详情 详情
(III) 44855   C13H18O5 详情 详情
(IV) 11176 3-Bromopropyne; 3-Bromo-1-propyne 106-96-7 C3H3Br 详情 详情
(V) 44856   C16H20O5 详情 详情
(VI) 19395 1-chloro-4-iodobenzene 637-87-6 C6H4ClI 详情 详情
(VII) 44857   C22H23ClO5 详情 详情
(VIII) 44858   C22H25ClO5 详情 详情
(IX) 44859   C23H29ClO6 详情 详情
(X) 10463 Benzoyl chloride 98-88-4 C7H5ClO 详情 详情
(XI) 44860   C30H33ClO7 详情 详情
(XII) 44861   C31H35ClO7 详情 详情
(XIII) 44862   C23H29ClO6 详情 详情
(XIV) 44863   C17H12N6O 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XIV)

Intermediate (XIV) can be obtained as follows: Bromination of methyl cinnamate (XV) with Br2 in CH2Cl2 provides 2,3-dibromo-3-phenylpropanoate (XVI), which is then converted into alpha-bromocinnamic ester (XVII) by reaction with Et3N in refluxing toluene. Treatment of (XVII) with imidazopyridine (XVIII) and NaH in DMF affords derivative (XIX), which is then hydrolyzed by treatment with NaOH in MeOH to furnish carboxylic acid (XX). Finally, (XX) reacts with carbonylditriazole in DMF to give the target intermediate (XIV).

1 Hemmerle, H.; Schubert, G.; Burger, H.-J.; Herling, A.; Efendic, S. (Aventis SA); Cyclohexane derivs., processes for their preparation and their use as glucose-6-phosphatase inhibitors. CA 2149007; CA 4416433; EP 0682024; JP 1995330767; US 5739147 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIV) 44863   C17H12N6O 详情 详情
(XV) 23888 methyl (E)-3-phenyl-2-propenoate 103-26-4 C10H10O2 详情 详情
(XVI) 44865 methyl 2,3-dibromo-3-phenylpropanoate C10H10Br2O2 详情 详情
(XVII) 44866 methyl (Z)-2-bromo-3-phenyl-2-propenoate C10H9BrO2 详情 详情
(XVIII) 44867 1H-imidazo[4,5-b]pyridine C6H5N3 详情 详情
(XIX) 44868 methyl (Z)-3-(1H-imidazo[4,5-b]pyridin-1-yl)-3-phenyl-2-propenoate C16H13N3O2 详情 详情
(XX) 44869 (Z)-3-(1H-imidazo[4,5-b]pyridin-1-yl)-3-phenyl-2-propenoic acid C15H11N3O2 详情 详情
(XXI) 44870 di(1H-1,2,4-triazol-1-yl)methanone C5H4N6O 详情 详情
Extended Information