5-bromo-2-furoic acid -Drug Synthesis Database

【结构式】

【分子编号】31326

【品名】5-bromo-2-furoic acid

【CA登记号】585-70-6

【分子式】C₅H₃BrO₃

【分子量】190.98102

【元素组成】C 31.45% H 1.58% Br 41.84% O 25.13%

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)

5-Bromo-2-furoic acid (I) was converted to the mixed anhydride with isobutyl chloroformate and then reduced to alcohol (II) using NaBH4. After formation of the sodium alkoxide of (II) with NaH, condensation with chloride (III) in the presence of 15-crown-5 provided ether (IV). Hydrolysis of the methyl ester of (IV), followed by coupling of the resulting carboxylic acid (V) with L-methionine methyl ester (VI) gave amide (VII). Further Suzuki coupling of (VII) with 4-chlorophenyl boronic acid (VIII) produced the aryl-substituted furan (IX). Finally, hydrolysis of the methionine methyl ester of (IX) with LiOH, followed by lyophilization furnished the corresponding lithium carboxylate salt.

参考文献中间体

合成目标

【1】 Augeri, D.J.; Kalvin, D.; Anowick, D.; et al.; Potent and orally bioavailable noncysteine-containing inhibitors of protein farnesyltransferase. Bioorg Med Chem Lett 1999, 9, 8, 1069.
【2】 Donner, B.G.; Janowick, D.A.; Larsen, J.J.; Rosenberg, S.H.; Hamilton, A.D.; Barr, K.J.; Sorensen, B.K.; Augeri, D.J.; Kalvin, D.M.; O'Connor, S.J.; Fakhoury, S.A.; Swenson, R.E.; Liu, G.; Sebti, S.M.; Shen, W. (University of Pittsburgh); Inhibitors of protein isoprenyl transferases. EP 0986384; WO 9850029; WO 9850030; WO 9850031 .

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)	31327	(5-bromo-2-furyl)methanol		C₅H₅BrO₂	详情	详情
(III)	31328	methyl 5-(chloromethyl)-2'-methyl[1,1'-biphenyl]-2-carboxylate		C₁₆H₁₅ClO₂	详情	详情
(IV)	31329	methyl 5-[[(5-bromo-2-furyl)methoxy]methyl]-2'-methyl[1,1'-biphenyl]-2-carboxylate		C₂₁H₁₉BrO₄	详情	详情
(V)	31330	5-[[(5-bromo-2-furyl)methoxy]methyl]-2'-methyl[1,1'-biphenyl]-2-carboxylic acid		C₂₀H₁₇BrO₄	详情	详情
(VI)	17950	D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride	21691-49-6	C₆H₁₃NO₂S	详情	详情
(VII)	31331	methyl (2S)-2-[[(5-[[(5-bromo-2-furyl)methoxy]methyl]-2'-methyl[1,1'-biphenyl]-2-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate		C₂₆H₂₈BrNO₅S	详情	详情
(VIII)	17575	4-chlorophenylboronic acid	1679-18-1	C₆H₆BClO₂	详情	详情
(IX)	31332	methyl (2S)-2-([[5-([[5-(4-chlorophenyl)-2-furyl]methoxy]methyl)-2'-methyl[1,1'-biphenyl]-2-yl]carbonyl]amino)-4-(methylsulfanyl)butanoate		C₃₂H₃₂ClNO₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

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