5-chloro-2-nitrobenzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】44133

【品名】5-chloro-2-nitrobenzoyl chloride

【CA登记号】

【分子式】C₇H₃Cl₂NO₃

【分子量】220.01116

【元素组成】C 38.21% H 1.37% Cl 32.23% N 6.37% O 21.82%

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：(I)

The condensation between 5-chloro-2-nitrobenzoyl chloride (I) and 2-amino-5-chloropyridine (II) produced the corresponding amide (III). Subsequent catalytic hydrogenation of the nitro group of (III) gave aniline (IV). Acid chloride (VI), prepared from N-Boc-isonipecotic acid (V) and oxalyl chloride, was then coupled to aniline (IV) to furnish amide (VII). Further trifluoroacetic acid-promoted cleavage of the Boc protecting group of (VII) yielded piperidine (VIII). Finally, reductive alkylation with acetone in the presence of sodium triacetoxyborohydride gave rise to the target N-isopropyl piperidine.

参考文献中间体

合成目标

【1】 Kyle, J.A.; et al.; SAR investigations of N-aryl-2-[(piperidin-4-ylcarbonyl)amino]benzamide factor Xa inhibitors. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 288.
【2】 Aromatic amides. WO 0039118 .

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)	44133	5-chloro-2-nitrobenzoyl chloride		C₇H₃Cl₂NO₃	详情	详情
(II)	18559	5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine	1072-98-6	C₅H₅ClN₂	详情	详情
(III)	44134	5-chloro-N-(5-chloro-2-pyridinyl)-2-nitrobenzamide		C₁₂H₇Cl₂N₃O₃	详情	详情
(IV)	44135	2-amino-5-chloro-N-(5-chloro-2-pyridinyl)benzamide		C₁₂H₉Cl₂N₃O	详情	详情
(V)	17404	1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid; 1-BOC-piperidine-4-carboxylic acid; N-Boc-isonipecotic acid	84358-13-4	C₁₁H₁₉NO₄	详情	详情
(VI)	44136	tert-butyl 4-(chlorocarbonyl)-1-piperidinecarboxylate		C₁₁H₁₈ClNO₃	详情	详情
(VII)	44137	tert-butyl 4-[(4-chloro-2-[[(5-chloro-2-pyridinyl)amino]carbonyl]anilino)carbonyl]-1-piperidinecarboxylate		C₂₃H₂₆Cl₂N₄O₄	详情	详情
(VIII)	44138	N-(4-chloro-2-[[(5-chloro-2-pyridinyl)amino]carbonyl]phenyl)-4-piperidinecarboxamide		C₁₈H₁₈Cl₂N₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The cyclization of 2-oxoacetic acid ethyl ester (I), 1-phenylethylamine (II) and cyclopentadiene (III) by means of BF3 and TFA in dichloromethane gives the 2-azabicyclo[2.2.1]heptene (IV), which is debenzylated with H2 over Pd/C in ethanol to yield 2-azabicyclo[2.2.1]hept-5-ene-3-carboxylic acid ethyl ester (V) The acylation of (V) with 5-chloro-2-nitrobenzoyl chloride (VI) and TEA in dichloromethane affords the bicyclic amide (VII), which is submitted to a reductive cyclization with Fe in refluxing acetic acid to afford the polycyclic benzodiazepinedione (VIII). The reduction of the carbonyl groups of (VIII) by means of LiAlH4 in THF provides the benzodiazepine (IX), which is acylated with 4-nitrobenzoyl chloride (X) and TEA in dichloromethane to give the polycyclic amide (XI). The reduction of the nitro group of (XI) with Zn and NH4Cl in refluxing methanol yields the corresponding amino derivative (XII), which is finally acylated with 4'-methylbiphenyl-2-carbonyl chloride (XIII) and TEA in dichloromethane to furnish the target polycyclic benzodiazepine.

参考文献中间体

合成目标

【1】 Dyatkin, A.B.; Demarest, K.; Look, R.; Maryanoff, B.E.; Hoekstra, W.J.; Gunnet, J.; Andrade-Gordon, P.; DeGaravilla, L.; Hlasta, D.J.; Structurally novel V2-selective and dual V1A/V2 vasopressin receptor antagonists. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 35.

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)	48591	Ethyl glyoxylate; Ethyl oxoacetate; Glyoxylic acid ethyl ester	924-44-7	C₄H₆O₃	详情	详情
(II)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(III)	15148	1-phenylethylamine; DL-a-methylbenzylamine; 1-phenyl-1-ethanamine	618-36-0	C₈H₁₁N	详情	详情
(IV)	54051	ethyl 2-(1-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate	n/a	C₁₇H₂₁NO₂	详情	详情
(V)	54052	ethyl 2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate	n/a	C₉H₁₃NO₂	详情	详情
(VI)	44133	5-chloro-2-nitrobenzoyl chloride		C₇H₃Cl₂NO₃	详情	详情
(VII)	54053	ethyl 2-(5-chloro-2-nitrobenzoyl)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate	n/a	C₁₆H₁₅ClN₂O₅	详情	详情
(VIII)	54054	6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraene-3,11-dione	n/a	C₁₄H₁₁ClN₂O₂	详情	详情
(IX)	54055	6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraene	n/a	C₁₄H₁₅ClN₂	详情	详情
(X)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(XI)	54056	(6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraen-10-yl)(4-nitrophenyl)methanone	n/a	C₂₁H₁₈ClN₃O₃	详情	详情
(XII)	54057	(4-aminophenyl)(6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraen-10-yl)methanone	n/a	C₂₁H₂₀ClN₃O	详情	详情
(XIII)	54058	4'-methyl[1,1'-biphenyl]-2-carbonyl chloride	n/a	C₁₄H₁₁ClO	详情	详情

Extended Information