2,4-dihydroxybenzaldehyde -Drug Synthesis Database

【结构式】

【分子编号】20094

【品名】2,4-dihydroxybenzaldehyde

【CA登记号】95-01-2

【分子式】C₇H₆O₃

【分子量】138.12284

【元素组成】C 60.87% H 4.38% O 34.75%

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)

7-Hydroxy-3-methylcoumarin (III) was obtained by Perkin reaction of 2,4-dihydroxybenzaldehyde (I) and propionic anhydride (II) in the presence of sodium propionate in pyridine. Alkylation of N-phenylpiperazine (IV) with 1-bromo-3-chloropropane (V) and NaOH in acetone provided the chloropropyl compond (VI), which was finally condensed with coumarin (III) using NaH in DMF.

参考文献中间体

合成目标

【1】 Antonello, C.; et al.; Synthesis and characterization of new methylpsoralens as potential photochemotherapeutic agents. Farmaco 1994, 49, 4, 277.
【2】 Teran, C.; Santana, L.; Uriarte, E.; Fall, Y.; Unelius, L.; Tolf, B.R.; Phenylpiperazine derivatives with strong affinity for 5HT1A, D2A and D3 receptors. Bioorg Med Chem Lett 1998, 8, 24, 3567.

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)	20094	2,4-dihydroxybenzaldehyde	95-01-2	C₇H₆O₃	详情	详情
(II)	20095	propionic anhydride	123-62-6	C₆H₁₀O₃	详情	详情
(III)	20096	7-hydroxy-3-methyl-2H-chromen-2-one		C₁₀H₈O₃	详情	详情
(IV)	10756	N-Phenylpiperazine; 1-Phenylpiperazine; Phenyl piperazine	92-54-6	C₁₀H₁₄N₂	详情	详情
(V)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(VI)	20099	1-(3-chloropropyl)-4-phenylpiperazine		C₁₃H₁₉ClN₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Nitrile (II) was prepared by reaction of 2,4-dihydroxybenzaldehyde (I) with nitroethane and NaOAc in boiling AcOH. Subsequent condensation with D-cysteine (III) in the presence of phosphate buffer at pH 5.95 in MeOH provided the title thiazolidine.

参考文献中间体

合成目标

【1】 Bergeron, R.J.; Wiegand, J.; Weimar, W.R.; Vinson, J.R.; Bussenius, J.; Yao, G.W.; McManis, J.S.; Desazadesmethyldesferrithiocin analogues as orally effective iron chelators. J Med Chem 1999, 42, 1, 95.
【2】 Bergeron, R.J. Jr. (University of Florida); Thiazoline acid derivs.. WO 0012493 .

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)	20094	2,4-dihydroxybenzaldehyde	95-01-2	C₇H₆O₃	详情	详情
(II)	25403	2,4-dihydroxybenzonitrile		C₇H₅NO₂	详情	详情
(III)	25404	D-cysteine; (S)-2-Amino-3-mercaptopropionic acid	921-01-7	C₃H₇NO₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The title compound has been prepared by two related ways. The alkylation of 2-fluoro-4-hydroxybenzonitrile (I) with 3,4-(methylenedioxy)benzyl chloride (II) afforded ether (III). This was coupled with (R,S)-2-hydroxy-2-(2-methylphenyl)acetic acid (IV) in the presence of NaH in DMSO to produce the racemic adduct (V). Resolution was then achieved by fractional crystallization of the diastereoisomeric salts with (-)-ephedrine to furnish the desired (S)-enantiomer, which was finally isolated as the corresponding sodium salt.

参考文献中间体

合成目标

【1】 Astles, P.C.; Brown, T.J.; Halley, F.; et al.; Selective ETA antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives. J Med Chem 2000, 43, 5, 900.
【2】 Porter, B.; Astles, P.C.; Bridge, A.W.; McLay, I.M.; Van Sickle, A.P.; Walsh, R.J.A.; McCarthy, C.; Morley, A.D.; Halley, F.; Harris, N.V.; Majid, T.N.; Smith, C. (Rhône-Poulenc Rorer Ltd.); Substd. phenyl cpds. as endothelin antagonists. US 6048893; US 6124343; WO 9622978 .

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)	20094	2,4-dihydroxybenzaldehyde	95-01-2	C₇H₆O₃	详情	详情
(II)	28617	5-(chloromethyl)-1,3-benzodioxole		C₈H₇ClO₂	详情	详情
(III)	38975	(3S,5R)-1-[(2S,4R)-5-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-4-benzyl-2-hydroxy-5-oxopentyl]-3,5-dibenzyl-2-pyrrolidinone		C₄₂H₄₆N₂O₄	详情	详情
(IV)	38977	2-hydroxy-2-(2-methylphenyl)acetic acid		C₉H₁₀O₃	详情	详情
(V)	38978	2-[5-(1,3-benzodioxol-5-ylmethoxy)-2-cyanophenoxy]-2-(2-methylphenyl)acetic acid		C₂₄H₁₉NO₆	详情	详情

合成路线4

该中间体在本合成路线中的序号：(VI)

In a related procedure, alkylation of 2,4-dihydroxybenzaldehyde (VI) with chloride (II) gave ether (VII). Subsequent conversion of the aldehyde group of (VII) into the desired nitrile (X) was effected by the following sequence, including formation of the corresponding oxime (VIII), dehydration with concomitant acetylation using Ac2O, and then hydrolysis of acetate (IX) using K2CO3. Alternatively, aldehyde (VII) was directly converted to nitrile (X) by reaction with hydroxylamine-O-sulfonic acid, followed by basic treatment. Racemic alpha-bromo-(2-methylphenyl)acetic acid (XI) was resolved via formation of the corresponding salt with (-)-ephedrine (XII). Hydroxy nitrile (X) was then alkylated with the chiral bromide (XII), and the resulting compound was finally converted to the corresponding sodium salt.

参考文献中间体

合成目标

【1】 Porter, B.; Astles, P.C.; Bridge, A.W.; McLay, I.M.; Van Sickle, A.P.; Walsh, R.J.A.; McCarthy, C.; Morley, A.D.; Halley, F.; Harris, N.V.; Majid, T.N.; Smith, C. (Rhône-Poulenc Rorer Ltd.); Substd. phenyl cpds. as endothelin antagonists. US 6048893; US 6124343; WO 9622978 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	28617	5-(chloromethyl)-1,3-benzodioxole		C₈H₇ClO₂	详情	详情
(VI)	20094	2,4-dihydroxybenzaldehyde	95-01-2	C₇H₆O₃	详情	详情
(VII)	38979	4-(1,3-benzodioxol-5-ylmethoxy)-2-hydroxybenzaldehyde		C₁₅H₁₂O₅	详情	详情
(VIII)	38980	4-(1,3-benzodioxol-5-ylmethoxy)-2-hydroxybenzaldehyde oxime		C₁₅H₁₃NO₅	详情	详情
(IX)	38981	5-(1,3-benzodioxol-5-ylmethoxy)-2-cyanophenyl acetate		C₁₇H₁₃NO₅	详情	详情
(X)	38982	4-(1,3-benzodioxol-5-ylmethoxy)-2-hydroxybenzonitrile		C₁₅H₁₁NO₄	详情	详情
(XI)	38983	2-bromo-2-(2-methylphenyl)acetic acid		C₉H₉BrO₂	详情	详情
(XII)	38984	(2R)-2-bromo-2-(2-methylphenyl)ethanoic acid		C₉H₉BrO₂	详情	详情

合成路线5

该中间体在本合成路线中的序号：(I)

The alkylation of 2-fluoro-4-hydroxybenzonitrile (I) with 4-picolyl chloride (II) afforded ether (III). This was coupled with (R,S)-2-hydroxy-2-(2-methylphenyl)acetic acid (IV) in the presence of NaH in DMSO to produce the racemic adduct (V). Resolution of (V) was then achieved by fractional crystallization of the diastereoisomeric salts with (-)-ephedrine to furnish the desired (S)-enantiomer, which was finally isolated as the corresponding sodium salt.

参考文献中间体

合成目标

【1】 Astles, P.C.; Brown, T.J.; Halley, F.; et al.; Selective ETA antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives. J Med Chem 2000, 43, 5, 900.
【2】 Porter, B.; Astles, P.C.; Bridge, A.W.; McLay, I.M.; Van Sickle, A.P.; Walsh, R.J.A.; McCarthy, C.; Morley, A.D.; Halley, F.; Harris, N.V.; Majid, T.N.; Smith, C. (Rhône-Poulenc Rorer Ltd.); Substd. phenyl cpds. as endothelin antagonists. US 6048893; US 6124343; WO 9622978 .

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)	20094	2,4-dihydroxybenzaldehyde	95-01-2	C₇H₆O₃	详情	详情
(II)	10844	4-(Chloromethyl)pyridine	10445-91-7	C₆H₆ClN	详情	详情
(III)	38985	2-fluoro-4-(4-pyridinylmethoxy)benzonitrile		C₁₃H₉FN₂O	详情	详情
(IV)	38977	2-hydroxy-2-(2-methylphenyl)acetic acid		C₉H₁₀O₃	详情	详情
(V)	38986	2-[2-cyano-5-(4-pyridinylmethoxy)phenoxy]-2-(2-methylphenyl)acetic acid		C₂₂H₁₈N₂O₄	详情	详情

Extended Information