2,4-difluorophenyl isocyanate; 2,4-difluoro-1-isocyanatobenzene -Drug Synthesis Database

【结构式】

【分子编号】23255

【品名】2,4-difluorophenyl isocyanate; 2,4-difluoro-1-isocyanatobenzene

【CA登记号】59025-55-7

【分子式】C₇H₃F₂NO

【分子量】155.1037664

【元素组成】C 54.21% H 1.95% F 24.5% N 9.03% O 10.32%

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：(VI)

The reaction of 4-neopentylbenzoic acid (I) with SOCl2 in refluxing dichloromethane gives the corresponding acid chloride (II) , which is condensed with heptylamine (III) in dichloromethane to yield 4-neopentyl-N-heptylbenzamide (IV). The reduction of (IV) with di(2-methoxyethoxy)sodium aluminum hydride in refluxing toluene affords 4-neopentyl-N-heptylbenzylamine (V), which is finally condensed with 2,4-difluorophenyl isocyanate (VI) in hexane. Compound (II) can also be obtained from neopentylbenzene (VII) and oxalyl chloride in the presence of aluminum chloride.

参考文献中间体

合成目标

【1】 Schaffer, S.A.; Dutia, M.D.; Largis, E.E.; Katocs, A.S. Jr.; Bloom, J.D.; Wang, C.-H.; De Vries, V.G.; Potential antiatherosclerotic agents. 5. And acyl-. J Med Chem 1986, 29, 1131.
【2】 De Vries, V.G. (American Cyanamid Co.); Antiatherosclerotic ureas and thioureas. BE 0900178; FR 2549473; GB 2149394; US 4623662 .
【3】 Castaner, J.; Prous, J.; CL-277082. Drugs Fut 1987, 12, 6, 527.

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)	23250	4-neopentylbenzoic acid		C₁₂H₁₆O₂	详情	详情
(II)	23251	4-neopentylbenzoyl chloride		C₁₂H₁₅ClO	详情	详情
(III)	23252	1-heptanamine; heptylamine	111-68-2	C₇H₁₇N	详情	详情
(IV)	23253	N-heptyl-4-neopentylbenzamide		C₁₉H₃₁NO	详情	详情
(V)	23254	N-(4-neopentylbenzyl)-1-heptanamine; N-heptyl-N-(4-neopentylbenzyl)amine		C₁₉H₃₃N	详情	详情
(VI)	23255	2,4-difluorophenyl isocyanate; 2,4-difluoro-1-isocyanatobenzene	59025-55-7	C₇H₃F₂NO	详情	详情
(VII)	28162	1-neopentylbenzene	1007-26-7	C₁₁H₁₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

4-Bromothiophenol (I) was alkylated with tert-butyl bromoisobutyrate (II) to give the bromoester (III). Heck reaction of (III) with vinylphthalimide (IV) produced adduct (V), which was hydrogenated in the presence of Wilkinson's catalyst to yield the arylethyl phthalimide (VI). Following phthalimide deprotection with hydrazine, the resulting primary amine (VII) was coupled with heptanoic acid using diisopropyl carbodiimide and hydroxybenzotriazole affording amide (VIII). Borane reduction of (VIII) furnished the secondary amine (IX), which was condensed with 2,4-difluorophenyl isocyanate (X) to give urea (XI). Finally, trifluoroacetic acid-promoted cleavage of the tert-butyl ester of (IX) provided the title carboxylic acid.

参考文献中间体

合成目标

【1】 Brown, P.J.; Winegar, D.A.; Plunket, K.D.; et al.; A ureido thiosobutyric acid (GW9578) is a subtype selective PPARalpha agonist with potent lipid lowering activity. J Med Chem 1999, 42, 19, 3785.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	35032	heptanoic acid	111-14-8	C₇H₁₄O₂	详情	详情
(I)	29626	4-bromophenylhydrosulfide; 4-bromobenzenethiol	106-53-6	C₆H₅BrS	详情	详情
(II)	34947	tert-butyl 2-bromo-2-methylpropanoate	23877-12-5	C₈H₁₅BrO₂	详情	详情
(III)	34948	tert-butyl 2-[(4-bromophenyl)sulfanyl]-2-methylpropanoate		C₁₄H₁₉BrO₂S	详情	详情
(IV)	32749	2-vinyl-1H-isoindole-1,3(2H)-dione	3485-84-5	C₁₀H₇NO₂	详情	详情
(V)	34949	tert-butyl 2-([4-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]phenyl]sulfanyl)-2-methylpropanoate		C₂₄H₂₅NO₄S	详情	详情
(VI)	34950	tert-butyl 2-([4-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]phenyl]sulfanyl)-2-methylpropanoate		C₂₄H₂₇NO₄S	详情	详情
(VII)	34951	tert-butyl 2-[[4-(2-aminoethyl)phenyl]sulfanyl]-2-methylpropanoate		C₁₆H₂₅NO₂S	详情	详情
(VIII)	34952	tert-butyl 2-([4-[2-(heptanoylamino)ethyl]phenyl]sulfanyl)-2-methylpropanoate		C₂₃H₃₇NO₃S	详情	详情
(IX)	34953	tert-butyl 2-([4-[2-(heptylamino)ethyl]phenyl]sulfanyl)-2-methylpropanoate		C₂₃H₃₉NO₂S	详情	详情
(X)	23255	2,4-difluorophenyl isocyanate; 2,4-difluoro-1-isocyanatobenzene	59025-55-7	C₇H₃F₂NO	详情	详情
(XI)	34954	tert-butyl 2-[(4-[2-[[(2,4-difluoroanilino)carbonyl](heptyl)amino]ethyl]phenyl)sulfanyl]-2-methylpropanoate		C₃₀H₄₂F₂N₂O₃S	详情	详情

Extended Information