3-(4-morpholinyl)-1-propanol -Drug Synthesis Database

【结构式】

【分子编号】54957

【品名】3-(4-morpholinyl)-1-propanol

【CA登记号】

【分子式】C₇H₁₅NO₂

【分子量】145.20164

【元素组成】C 57.9% H 10.41% N 9.65% O 22.04%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

Racemic amide (VI) was also prepared by a closely related procedure. Coupling of keto acid (XII) with tetrahydropyridine (V) using DCC gave keto amide (XIII), which was then protected as the ethylene ketal (VI) upon treatment with 2-methoxy-1,3-dioxolane (XIV) in the presence of methanesulfonic acid.

参考文献中间体

合成目标

【1】 Wright, J.L.; et al.; The discovery and structure-activity relationships of 1,2,3, 6-tetrahydro-4-phenyl-1-[(arylcyclohexenyl)alkyl]pyridines. Dopamine autoreceptor agonists and potential antipsychotic agents. J Med Chem 1994, 37, 21, 3523.

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)	54943	3-oxocyclohexanecarboxylic acid		C₇H₁₀O₃	详情	详情
(II)	13002	4-Phenyl-1,2,3,6-tetrahydropyridine; 1,2,3,6-Tetrahydro-4-phenyl-pyridine	10338-69-9	C₁₁H₁₃N	详情	详情
(III)	54944	3-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]carbonyl}cyclohexanone		C₁₈H₂₁NO₂	详情	详情
(IV)	54945	2-Methoxy-1,3-dioxolane	19693-75-5	C₄H₈O₃	详情	详情
(V)	54957	3-(4-morpholinyl)-1-propanol		C₇H₁₅NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

4-Chloro-7-fluoro-6-nitroquinazoline (I) was condensed with 3-chloro-4-fluoroaniline (II) to afford the 4-anilino quinazoline (III). Displacement of the activated fluorine of (III) with the potassium alkoxide of morpholinopropanol (IV) gave the morpholinopropyl ether (V). Subsequent reduction of the nitro group of (V), either using iron dust and acetic acid or catalytic hydrogenation over Raney-Ni, furnished aminoquinazoline (VI). This was finally condensed with acrylic acid (VII), via activation as the mixed anhydride with isobutyl chloroformate or using EDC as the coupling reagent, to provide the title acrylamide.

参考文献中间体

合成目标

【1】 Loo, J.A.; Rewcastle, G.W.; Smaill, J.B.; et al.; Tyrosine kinase inhibitors.17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(Phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides baring additional solubilizing functions. J Med Chem 2000, 43, 7, 1380.
【2】 Bridges, A.J.; Klohs, W.D.; Driscoll, D. (Pfizer Inc.); N-[4-(3-Chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases. EP 1131304; US 6344455; WO 0031048 .

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)	19142	4-chloro-7-fluoro-6-nitroquinazoline		C₈H₃ClFN₃O₂	详情	详情
(II)	18688	3-Chloro-4-fluorophenylamine; 3-Chloro-4-fluoroaniline	367-21-5	C₆H₅ClFN	详情	详情
(III)	54956	N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-4-quinazolinamine; N-(3-chloro-4-fluorophenyl)-N-(7-fluoro-6-nitro-4-quinazolinyl)amine	162012-67-1	C₁₄H₇ClF₂N₄O₂	详情	详情
(IV)	54957	3-(4-morpholinyl)-1-propanol		C₇H₁₅NO₂	详情	详情
(V)	54958	N-(3-chloro-4-fluorophenyl)-7-[3-(4-morpholinyl)propoxy]-6-nitro-4-quinazolinamine; N-(3-chloro-4-fluorophenyl)-N-{7-[3-(4-morpholinyl)propoxy]-6-nitro-4-quinazolinyl}amine		C₂₁H₂₁ClFN₅O₄	详情	详情
(VI)	54959	N-{6-amino-7-[3-(4-morpholinyl)propoxy]-4-quinazolinyl}-N-(3-chloro-4-fluorophenyl)amine; N~4~-(3-chloro-4-fluorophenyl)-7-[3-(4-morpholinyl)propoxy]-4,6-quinazolinediamine		C₂₁H₂₃ClFN₅O₂	详情	详情
(VII)	19139	acrylic acid	79-10-7	C₃H₄O₂	详情	详情

Extended Information