5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】19964

【品名】5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid

【CA登记号】5326-47-6

【分子式】C₇H₆INO₂

【分子量】263.03465

【元素组成】C 31.96% H 2.3% I 48.25% N 5.33% O 12.17%

与该中间体有关的原料药合成路线共 5 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

该中间体在本合成路线中的序号：(I)

The cyclization of 2-amino-5-iodobenzoic acid (I) with pentanoic anhydride (II) in basic medium gives 2-butyl-6-iodoquinazolin-4(3H)-one (III), which is condensed with CO and methanol by means of PdCl2(PPh3)2 and TEA yielding 2-butyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid methyl ester (IV). The Grignard condensation of (IV) with methylmagnesium bromide affords the tertiary alcohol (V), which is finally condensed with the tetrazolylbiphenyl (VI) by means of LiOMe, methylated at the tertiary alcohol with methyl iodide and NaH, and deprotected with NaOH in methanol/THF.

参考文献中间体

合成目标

【1】 Levin, J.I.; Chen, P.S.; Porter, R.S.; 2,3,6-Substituted quinazolinones as angiotensin II receptor antagonists. Drugs Fut 1995, 20, 1, 55.

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)	19964	5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid	5326-47-6	C₇H₆INO₂	详情	详情
(II)	27683	pentanoic anhydride	2082-59-9	C₁₀H₁₈O₃	详情	详情
(III)	41190	2-butyl-6-iodo-4(3H)-quinazolinone		C₁₂H₁₃IN₂O	详情	详情
(IV)	41191	methyl 2-butyl-4-oxo-3,4-dihydro-6-quinazolinecarboxylate		C₁₄H₁₆N₂O₃	详情	详情
(V)	41192	2-butyl-6-(1-hydroxy-1-methylethyl)-4(3H)-quinazolinone		C₁₅H₂₀N₂O₂	详情	详情
(VI)	15538	5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-2-trityl-2H-1,2,3,4-tetraazole	124750-51-2	C₃₃H₂₅BrN₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The cyclization of 2-amino-5-iodobenzoic acid (I) with an excess of refluxing trifluoroacetic anhydride (II) by means of triethylamine gives 6-iodo-2-(trifluoromethyl)-3,1-benzoxazin-4-one (III), which is treated with conc. aqueous NH4OH to afford 6-iodo-2-(trifluoromethyl)quinazolin-4(3H)-one (IV). The reaction of (IV) with refluxing POCl3 yields 4-chloro-6-iodo-2-(trifluoromethyl)quinazoline (V), which is finally condensed with 1-Ethylpiperidine-3-amine (VI) by means of triethylamine in ether.

参考文献中间体

合成目标

【1】 Ahn, K.; Cheng, X.-M.; Doherty, A.M.; Elslager, E.F.; Kornberg, B.; Lee, C.; Leonard, D.; Nikam, S.S.; Werbel, L.M. (Pfizer Inc.); Quinazolines as inhibitors of endothelin converting enzyme. EP 0799221; JP 1998510834; US 5658902; WO 9619474 .

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)	19964	5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid	5326-47-6	C₇H₆INO₂	详情	详情
(III)	19965	6-iodo-2-(trifluoromethyl)-4H-3,1-benzoxazin-4-one		C₉H₃F₃INO₂	详情	详情
(IV)	19966	6-iodo-2-(trifluoromethyl)-4(3H)-quinazolinone		C₉H₄F₃IN₂O	详情	详情
(V)	19967	4-chloro-6-iodo-2-(trifluoromethyl)quinazoline		C₉H₃ClF₃IN₂	详情	详情
(VI)	19968	1-ethyl-3-piperidinamine; 1-ethyl-3-piperidinylamine		C₇H₁₆N₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Condensation of 2-amino-4-iodobenzoic acid (I) with 2-chloronicotinic acid (II) in refluxing EtOH in the presence of HCl yields pyridoquinazoline acid derivative (III), which is then condensed with N,N-dimethylethylenediamine (IV) in CH2Cl2 using BOP as coupling reagent to provide (V). Reaction of 2-bromopyridine (VI) in Et2O with n-BuLi and trimethylborate, followed by treatment with EtOH and HOAc, gives 3-pyridinyl boronic acid (VII), which is finally coupled to (V) in an Na2CO3 solution via a Suzuki coupling catalyzed by Pd(PPh3)4.

参考文献中间体

合成目标

【1】 Kitchen, D.B.; Schow, S.R.; Casscles, W.T. Jr.; Discafani, C.; Trova, M.P.; Lassota, P.; Zhang, N.; Powell, D.W.; Hetero biarylpyridoquinazolinone derivatives as anticancer agents. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 59.
【2】 Trova, M.P.; Zhang, N. (American Cyanamid Co.); Hetero-biaryl-pyridoquinazolinone derivs. as anti-cancer agents. EP 0944628; WO 9823617 .
【3】 Trova, M.P.; Zhang, N. (American Cyanamid Co.); Hetero-biaryl-pyridoquinazolinone derivs. as anti-cancer agents. US 5908840 .

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)	19964	5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid	5326-47-6	C₇H₆INO₂	详情	详情
(II)	28824	2-Chloropyridine-3-carboxylic acid; 2-Chloronicotinic acid	2942-59-8	C₆H₄ClNO₂	详情	详情
(III)	42991	2-iodo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxylic acid		C₁₃H₉IN₂O₃	详情	详情
(IV)	14881	N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine	108-00-9	C₄H₁₂N₂	详情	详情
(V)	42992	N-[2-(dimethylamino)ethyl]-2-iodo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxamide		C₁₇H₁₉IN₄O₂	详情	详情
(VI)	13265	3-Bromopyridine	626-55-1	C₅H₄BrN	详情	详情
(VII)	38825	3-pyridinylboronic acid	1692-25-7	C₅H₆BNO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

5-Iodoanthranilic acid (I) was converted to ethyl ester (II) (1), which was subsequently reacted with ethoxysuccinyl chloride (III) to furnish the amide (IV). Dieckmann cyclization of (IV) using KH produced ketoester (V), and further dealkoxycarbonylation by heating in wet DMSO gave rise to benzazepinedione (VI). After formation of the corresponding hydrazone (VIII) with 4-(trifluoromethyl)phenylhydrazine (VII), Fisher indole synthesis yielded the paulone system (IX). The Heck reaction of (IX) with acrylonitrile in the presence of palladium catalyst gave adduct (X). The target saturated analogue was finally prepared by refluxing the acrylonitrile derivative (X) with Mg in MeOH.

参考文献中间体

合成目标

【1】 Kunick, C.; Jalluri, R.K.; Sausville, E.A.; Gussio, R.; Zaharevitz, D.W.; Meijer, L.; Lemdke, T.; schultz, C.; Leost, M.; 2-Substituted paullones: CDK1/cyclin B-inhibiting property and in vitro antiproliferative activity. Bioorg Med Chem Lett 2000, 10, 6, 567.
【2】 Gussio, R.; Zaharevitz, D.W.; Sausville, E.A.; Jalluri, R.K. (US Department of Health & Human Services); Fused azepinone cyclin dependent kinase inhibitors. WO 9965910 .

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)	19964	5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid	5326-47-6	C₇H₆INO₂	详情	详情
(II)	40683	ethyl 2-amino-5-iodobenzoate		C₉H₁₀INO₂	详情	详情
(III)	40684	ethyl 4-chloro-4-oxobutanoate; Ethyl succinyl chloride	14794-31-1	C₆H₉ClO₃	详情	详情
(IV)	40685	ethyl 2-[(4-ethoxy-4-oxobutanoyl)amino]-5-iodobenzoate		C₁₅H₁₈INO₅	详情	详情
(V)	40686	ethyl 5-hydroxy-7-iodo-2-oxo-2,3-dihydro-1H-1-benzazepine-4-carboxylate		C₁₃H₁₂INO₄	详情	详情
(VI)	40687	7-iodo-3,4-dihydro-1H-1-benzazepine-2,5-dione		C₁₀H₈INO₂	详情	详情
(VII)	40688	1-[4-(trifluoromethyl)phenyl]hydrazine	368-90-1	C₇H₇F₃N₂	详情	详情
(VIII)	40689	7-iodo-3,4-dihydro-1H-1-benzazepine-2,5-dione 5-[N-[4-(trifluoromethyl)phenyl]hydrazone]		C₁₇H₁₃F₃IN₃O	详情	详情
(IX)	40690	2-iodo-9-(trifluoromethyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one		C₁₇H₁₀F₃IN₂O	详情	详情
(X)	40691	(E)-3-[6-oxo-9-(trifluoromethyl)-5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepin-2-yl]-2-propenenitrile		C₂₀H₁₂F₃N₃O	详情	详情

合成路线5

该中间体在本合成路线中的序号：(VI)

参考文献中间体

合成目标

【1】 Tung R. 2008. Preparation of 4-aminoquinazolines as EGFR and HER-2 inhibitors. PCT Int Appl WO 2008024439(Concert Pharmaceuticals Inc, USA).

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)	31326	5-bromo-2-furoic acid	585-70-6	C₅H₃BrO₃	详情	详情
(II)	67215	N,O-dimethylhydroxylamine hydrochloride		C₂H₈NO.HCl	详情	详情
(III)	67216	5-bromo-N-methoxy-N-methylfuran-2-carboxamide		C₇H₈BrNO₃	详情	详情
(IV)	52428	Bis(tributyltin); Hexabutyldistannane; Bis(tri-n-butyltin); Hexa-n-butylditin; Hexa-n-butyldistannane	813-19-4	C₂₄H₅₄Sn₂	详情	详情
(V)	67217	N-methoxy-N-methyl-5-(tributylstannyl)furan-2-carboxamide		C₁₉H₃₅NO₃Sn	详情	详情
(VI)	19964	5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid	5326-47-6	C₇H₆INO₂	详情	详情
(VII)	16598	Formamide	75-12-7	CH₃NO	详情	详情
(VIII)	67218	6-iodoquinazolin-4(1H)-one	16064-08-7	C₈H₅IN₂O	详情	详情
(IX)	49875	4-chloro-6-iodoquinazoline	98556-31-1	C₈H₄ClIN₂	详情	详情
(X)	67219			C₁₀H₉N.K	详情	详情
(XI)	67220	2-(2-bromoethyl)isoindoline-1,3-dione		C₁₂H₄D₄BrNO₂	详情	详情
(XII)	67221	iodomethane		CD₃I	详情	详情
(XIII)	67222	2-(2-(methylthio)ethyl)isoindoline-1,3-dione		C₁₁H₄D₇NO₂S	详情	详情
(XIV)	13214	Di-tert-butyldicarbonate; Dicarbonic acid bis(1,1-dimethylethyl) ester; dicarbonic acid di-tert-butyl ester pyrocarbonic acid di-tert-butyl ester; bis(1,1-dimethylethyl) dicarbonate di-tert-butyl pyrocarbonate	24424-99-5	C₁₀H₁₈O₅	详情	详情
(XV)	67223	tert-butyl (2-(methylsulfonyl)ethyl)carbamate		C₈H₁₀D₇NO₄S	详情	详情
(XVI)	67224	2-(methylsulfonyl)ethanamine hydrochloride		C₃H₂D₇NO₂S.HCl	详情	详情
(XVII)	49872	1-Chloro-2-Hydroxy-5-Nitrobenzene; 2-Chloro-4-nitrophenol; 4-Nitro-2-chlorophenol; p-Nitro-o-chlorophenol	619-08-9	C₆H₄ClNO₃	详情	详情
(XVIII)	17221	3-Fluorobenzyl bromide; 1-(bromomethyl)-3-fluorobenzene	456-41-7	C₇H₆BrF	详情	详情
(XIX)	49873	2-chloro-1-[(3-fluorobenzyl)oxy]-4-nitrobenzene; 2-chloro-4-nitrophenyl 3-fluorobenzyl ether		C₁₃H₉ClFNO₃	详情	详情
(XX)	49874	3-chloro-4-[(3-fluorobenzyl)oxy]phenylamine; 3-chloro-4-[(3-fluorobenzyl)oxy]aniline		C₁₃H₁₁ClFNO	详情	详情
(XXI)	49876	N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-N-(6-iodo-4-quinazolinyl)amine; N-[3-chloro-4-[(3-fluorobenzyl)oxy]phenyl]-6-iodo-4-quinazolinamine		C₂₁H₁₄ClFIN₃O	详情	详情
(XXII)	67225	5-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl)-N-methoxy-N-methyltetrahydrofuran-2-carboxamide		C₂₈H₂₆ClFN₄O₄	详情	详情
(XXIII)	67226	5-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl)tetrahydrofuran-2-carbaldehyde		C₂₆H₂₀DClFN₃O₃	详情	详情
(XXIV)	67227	tert-butyl ((5-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl)tetrahydrofuran-2-yl)methyl)(2-(methylsulfonyl)ethyl)carbamate		C₃₄H₂₇D₉ClFN₄O₆S	详情	详情
(XXV)	67228	4-methylbenzenesulfonic acid	104-15-4	C₇H₈O₃S	详情	详情

Extended Information