2-amino-3,6-difluorobenzenecarboximidamide -Drug Synthesis Database

【结构式】

【分子编号】63411

【品名】2-amino-3,6-difluorobenzenecarboximidamide

【CA登记号】

【分子式】C₇H₇F₂N₃

【分子量】171.1496064

【元素组成】C 49.12% H 4.12% F 22.2% N 24.55%

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：(IV)

Displacement of the 2-fluoro group in 2,3,6-trifluorobenzonitrile (I) with aqueous ammonia leads to 2-amino-3,6-difluorobenzonitrile (II). Addition of hydroxylamine to the nitrile (II) in the presence of NaOMe affords benzamidoxime (III). Subsequent catalytic hydrogenation of (III) over Raney nickel furnishes benzamidine (IV).

参考文献中间体

合成目标

【1】 Tinker, A.C.; Beaton, H.G.; Boughton-Smith, N.; Cook, T.R.; Cooper, S.L.; Fraser-Rae, L.; Hallam, K.; Hamley, P.; McInally, T.; Nicholls, D.J.; Pimm, A.D.; Wallace, A.V.; 1,2-Dihydro-4-quinazolinamines: Potent, highly selective inhibitors of inducible nitric oxide synthase which show antiinflammatory activity in vivo. J Med Chem 2003, 46, 6, 913.
【2】 Hamley, P.R.J.; Pimm, A.D.; Tinker, A.C.; Beaton, H.G.; McInally, T. (AstraZeneca plc); Pharmaceutically active quinazoline cpds.. EP 0858451; JP 1999513679; WO 9714686 .

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)	63408	2,3,6-trifluorobenzonitrile	136514-17-5	C₇H₂F₃N	详情	详情
(II)	63409	2-amino-3,6-difluorobenzonitrile	190011-81-5	C₇H₄F₂N₂	详情	详情
(III)	63410	2-amino-3,6-difluoro-N'-hydroxybenzenecarboximidamide		C₇H₇F₂N₃O	详情	详情
(IV)	63411	2-amino-3,6-difluorobenzenecarboximidamide		C₇H₇F₂N₃	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-Piperidone ethylene ketal (V) is acylated with 6-bromonicotinic acid (VI) employing 1,1'-carbonyldiimidazole to yield amide (VII). The bromide group of (VII) is then displaced with CuCN in hot DMF producing nitrile (VIII). Finally, condensation between N-acylpiperidone (VIII) and amidine (IV) in refluxing EtOH leads to the target spiro quinazoline.

参考文献中间体

合成目标

【1】 Tinker, A.C.; Beaton, H.G.; Boughton-Smith, N.; Cook, T.R.; Cooper, S.L.; Fraser-Rae, L.; Hallam, K.; Hamley, P.; McInally, T.; Nicholls, D.J.; Pimm, A.D.; Wallace, A.V.; 1,2-Dihydro-4-quinazolinamines: Potent, highly selective inhibitors of inducible nitric oxide synthase which show antiinflammatory activity in vivo. J Med Chem 2003, 46, 6, 913.
【2】 Hamley, P.R.J.; Pimm, A.D.; Tinker, A.C.; Beaton, H.G.; McInally, T. (AstraZeneca plc); Pharmaceutically active quinazoline cpds.. EP 0858451; JP 1999513679; WO 9714686 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	63411	2-amino-3,6-difluorobenzenecarboximidamide		C₇H₇F₂N₃	详情	详情
(V)	11338	1,4-Dioxa-8-azaspiro[4.5]decane; 4-Piperidone ethylene ketal	177-11-7	C₇H₁₃NO₂	详情	详情
(VI)	63412	6-bromonicotinic acid		C₆H₄BrNO₂	详情	详情
(VII)	63413	(6-bromo-3-pyridinyl)(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)methanone		C₁₃H₁₅BrN₂O₃	详情	详情
(VIII)	63414	5-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-2-pyridinecarbonitrile		C₁₄H₁₅N₃O₃	详情	详情

Extended Information