3,4-dimethylbenzaldehyde -Drug Synthesis Database

【结构式】

【分子编号】46036

【品名】3,4-dimethylbenzaldehyde

【CA登记号】5973-71-7

【分子式】C₉H₁₀O

【分子量】134.1778

【元素组成】C 80.56% H 7.51% O 11.92%

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：(A)

Dithiane intermediate (LII). The ozonolysis of the allylic diol (XLVIII) with O3 and PPh3 in dichloromethane/methanol gives the aldehyde (XLIX), which is condensed with propane-1,3-dithiol (L) by means of BF3/OEt2 in dichloromethane to yield the dihydroxylated 1,3-dithiane derivative (LI). Finally, this compound is protected with 3,4-Dmp-CHO (A) and PPTS to afford the desired dithiane intermediate (LII).

参考文献中间体

合成目标

【1】 Smith, A.B.; et al.; The spongistatins: Architecturally complex natural products - Part one: A formal synthesis of (+)-spongistatin 1 by construction of an advanced ABCD fragment. Angew Chem. Int Ed 2001, 40, 1, 191.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	46036	3,4-dimethylbenzaldehyde	5973-71-7	C₉H₁₀O	详情	详情
(XVIII)	64636	(2R,3R,4R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2,4-dimethyl-5-hexen-3-ol		C₁₄H₃₀O₂Si	详情	详情
(XLIX)	64637	(2S,3S,4R)-5-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-2,4-dimethylpentanal		C₁₃H₂₈O₃Si	详情	详情
(L)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(LI)	64638	(2R,3S,4S)-4-(1,3-dithian-2-yl)-2-methyl-1,3-pentanediol		C₁₀H₂₀O₂S₂	详情	详情
(LII)	64639	(4S,5R)-2-(3,4-dimethylphenyl)-4-[(1S)-1-(1,3-dithian-2-yl)ethyl]-5-methyl-1,3-dioxane		C₁₉H₂₈O₂S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Knoevenagel condensation of 3,4-dimethylbenzaldehyde (I) with malonic acid in the presence of piperidine afforded dimethylcinnamic acid (II), which was reduced to the saturated acid (III) by catalytic hydrogenation. Conversion of (III) to the corresponding acid chloride, followed by Friedel-Crafts cyclization, gave rise to the 1-indanone (IV). This was isomerized to the desired 2-indanone (VII) by the sequence of ketone reduction, followed by acidic dehydration of the resulting alcohol to give indene (V), which was converted to epoxide (VI) and then Lewis-acid promoted rearrangement to the 2-indanone (VII). Condensation of ketone (VII) with benzylamine and subsequent addition of trimethylsilyl cyanide to the resulting imine furnished amino nitrile (VIII). After reduction of (VIII) to the diamine (IX) with LiAlH4, the N-benzyl group was removed by transfer hydrogenolysis, yielding (X). Condensation of diamine (X) with formamidine acetate produced the target imidazoline, which was finally isolated as the fumarate salt.

参考文献中间体

合成目标

【1】 Lacoste, J.-M.; Verbeuren, T.J.; Cordi, A.; Descombes, J.-J.; Couchay, C.; Spiro[(1,3-diazacyclopent-1-ene)-5,2'-(5',6'-dimethylindane)]: A new alpha-adrenergic partial agonist. Two synthetic approaches. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PA-83.
【2】 Cordi, A.; Lacoste, J.-M.; Laubie, M.; Verbeuren, T.; Descombes, J.-J. (ADIR et Cie.); Benzospiroalkene derivs., process for their preparation and pharmaceutical compsns. containing them. CA 2128359; EP 0635497; FR 2709306; JP 1995304753; US 5436261 .

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)	46036	3,4-dimethylbenzaldehyde	5973-71-7	C₉H₁₀O	详情	详情
(II)	46037	(Z)-3-(3,4-dimethylphenyl)-2-propenoic acid		C₁₁H₁₂O₂	详情	详情
(III)	40285	3-(3,4-dimethylphenyl)propionic acid		C₁₁H₁₄O₂	详情	详情
(IV)	46038	5,6-dimethyl-1-indanone		C₁₁H₁₂O	详情	详情
(V)	46039	5,6-dimethyl-1H-indene		C₁₁H₁₂	详情	详情
(VI)	46040	3,4-dimethyl-6,6a-dihydro-1aH-indeno[1,2-b]oxirene		C₁₁H₁₂O	详情	详情
(VII)	46041	5,6-dimethyl-1,3-dihydro-2H-inden-2-one		C₁₁H₁₂O	详情	详情
(VIII)	46042	2-(benzylamino)-5,6-dimethyl-2-indanecarbonitrile		C₁₉H₂₀N₂	详情	详情
(IX)	46043	N-[2-(aminomethyl)-5,6-dimethyl-2,3-dihydro-1H-inden-2-yl]-N-benzylamine; 2-(aminomethyl)-N-benzyl-5,6-dimethyl-2-indanamine		C₁₉H₂₄N₂	详情	详情
(X)	46044	2-(aminomethyl)-5,6-dimethyl-2-indanamine; (2-amino-5,6-dimethyl-2,3-dihydro-1H-inden-2-yl)methylamine		C₁₂H₁₈N₂	详情	详情

Extended Information