4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione -Drug Synthesis Database

【结构式】

【分子编号】25549

【品名】4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione

【CA登记号】4160-82-1

【分子式】C₇H₁₀O₃

【分子量】142.1546

【元素组成】C 59.14% H 7.09% O 33.76%

与该中间体有关的原料药合成路线共 4 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1

该中间体在本合成路线中的序号：(III)

This compound has been obtained by two related ways: The reduction of 4-[4-(2-pyrimidinyl)piperazin-1-yl]butyronitrile (I) by means of RaNi and hydrazine in isopropanol gives 4-[4-(2-pyrimidinyl)piperazin-1-yl]butylamine (II), which is then condensed with 3,3-dimethylglutaric anhydride (III) in refluxing xylene or refluxing toluene to yield the target glutarimide derivative. Alternatively, the condensation of N-(4-bromobutyl)-3,3-dimethylglutarimide (IV) with 1-(2-pyrimidinyl)piperazine (V) by means of K2CO3 in refluxing acetonitrile also yields the target glutarimide derivative.

参考文献中间体

合成目标

【1】 Yevich, J.P.; et al.; Buspirone analogues. 1. Structure-activity relationships in a series of N-aryl- and heteroarylpiperazine derivatives. J Med Chem 1983, 26, 2, 194.
【2】 Temple, D.L. Jr. (Bristol-Myers Squibb Co.); 2-[4-[(4,4-Dialkyl-2,6-piperidinedion-1-yl)butyl]-1-piperazinyl]pyrimidines. BE 0895504; CH 656383; DE 3248160; FR 2518993; GB 2114122; JP 1983118582; JP 1994293753; US 4423049 .

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)	11180	4-[4-(2-Pyrimidinyl)piperazino]butanenitrile		C₁₂H₁₇N₅	详情	详情
(II)	11181	4-[4-(2-Pyrimidinyl)piperazino]butylamine; 4-[4-(2-Pyrimidinyl)piperazino]-1-butanamine	33386-20-8	C₁₂H₂₁N₅	详情	详情
(III)	25549	4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione	4160-82-1	C₇H₁₀O₃	详情	详情
(IV)	56851	1-(4-bromobutyl)-4,4-dimethyl-2,6-piperidinedione		C₁₁H₁₈BrNO₂	详情	详情
(V)	11175	2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine	20980-22-7	C₈H₁₂N₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The target diester was obtained by condensation of betulin (I) with an excess of 3,3-dimethyl glutaric anhydride (II) in the presence of 4-(dimethylamino)pyridine in pyridine at 95 C.

参考文献中间体

合成目标

【1】 Sun, I.-C.; Wang, H.-K.; Kashiwada, Y.; Shen, J.-K.; Cosentino, L.M.; Chen, C.-H.; Yang, L.-M.; Lee, K.-H.; Anti-AIDS agents. 34. Synthesis and structure-activity relationships of betulin derivatives as anti-HIV agents. J Med Chem 1998, 41, 23, 4648.
【2】 Sun, I.C.; Shen, J.K.; Wang, H.K.; Cosentino, L.M.; Lee, K.H.; Anti-AIDS agents. 32. Synthesis and anti-HIV activity of betulin derivatives. Bioorg Med Chem Lett 1998, 8, 10, 1267-1272.
【3】 Sun, I.-C.; Cosentino, L.M.; Lee, K.-H.; Wang, H.-K. (BBI Biotech Research Laboratories, Inc.; University of North Carolina); Acylated betulin and dihydrobetulin derivs., preparation thereof and use thereof. US 6172110 .

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)	25548	(1R,3aS,5aR,5bR,9S,11aR)-3a-(hydroxymethyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-ol	473-98-3	C₃₀H₅₀O₂	详情	详情
(II)	25549	4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione	4160-82-1	C₇H₁₀O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

The reaction of 2-(4-methylphenyl)acetic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which is condensed with thiophene (III) by means SnCl4 yielding 2-(4-methylphenyl)-1-(2-thienyl)ethanone (IV). The reduction of (IV) with hydrazine and KOH in hot triethylene glycol affords 2-[2-(4-methylphenyl)ethyl]thiophene (V), which is condensed with 3,3-dimethylglutaric anhydride (VI), by means of AlCl3 in hot nitrobenzene giving the 5-oxopentanoic acid derivative (VII). The reduction of (VII) with hydrazine and KOH as before yields the pentanoic acid derivative (VIII), which is condensed with 4-(2,3,4-trimethoxybenzyl)piperazine (IX) by means of oxalyl chloride to afford the acyl piperazine (X). Finally, the amide group of (X) is reduced with LiAlH4 in ethyl ether.

参考文献中间体

合成目标

【1】 Wierzbicki, M.; et al.; Amino derivatives of phenyl alkyl thiophene as inhibitors of bone resorption. Structure-activity relationship. Arzneim-Forsch Drug Res 1998, 48, 8, 840.
【2】 Wierzbicki, M.; Sauveur, F.; Bonnet, J.; Brisset, M.; Tordjman, C. (ADIR et Cie.); Thiophene derivs., process for their preparation and pharmaceutical compsns. containing them. AU 9166901; EP 0429370; FR 2655043; JP 1991190872; US 5061704 .

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)	28316	2-(4-methylphenyl)acetic acid	622-47-9	C₉H₁₀O₂	详情	详情
(II)	21017	2-(4-methylphenyl)acetyl chloride	35675-44-6	C₉H₉ClO	详情	详情
(III)	13297	Thiophene	110-02-1	C₄H₄S	详情	详情
(IV)	28317	2-(4-methylphenyl)-1-(2-thienyl)-1-ethanone		C₁₃H₁₂OS	详情	详情
(V)	28318	2-(4-methylphenethyl)thiophene		C₁₃H₁₄S	详情	详情
(VI)	25549	4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione	4160-82-1	C₇H₁₀O₃	详情	详情
(VII)	28319	3,3-dimethyl-5-[5-(4-methylphenethyl)-2-thienyl]-5-oxopentanoic acid		C₂₀H₂₄O₃S	详情	详情
(VIII)	28320	3,3-dimethyl-5-[5-(4-methylphenethyl)-2-thienyl]pentanoic acid		C₂₀H₂₆O₂S	详情	详情
(IX)	24354	2,3-dimethoxy-4-(1-piperazinylmethyl)phenyl methyl ether		C₁₄H₂₂N₂O₃	详情	详情
(X)	28321	3,3-dimethyl-5-[5-(4-methylphenethyl)-2-thienyl]-1-[4-(2,3,4-trimethoxybenzyl)-1-piperazinyl]-1-pentanone		C₃₄H₄₆N₂O₄S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(VI)

The reaction of 3-(4-methylphenyl)propionic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which is condensed with thiophene (III) by means SnCl4 yielding 3-(4-methylphenyl)-1-(2-thienyl)propan-1-one (IV). The reduction of (IV) with hydrazine and KOH in hot triethylene glycol affords 2-[3-(4-methylphenyl)propyl]thiophene (V), which is condensed with 3,3-dimethyl glutaric anhydride (VI), by means of AlCl3 in hot nitrobenzene giving the 5-oxopentanoic acid derivative (VII). The reduction of (VII) with hydrazine and KOH as before yields the pentanoic acid derivative (VIII), which is condensed with 4-(2,3,4-trimethoxybenzyl)piperazine (IX) by means of oxalyl chloride to afford the acyl piperazine (X). Finally, the amide group of (X) is reduced with LiAlH4 in ethyl ether.

参考文献中间体

合成目标

【1】 Wierzbicki, M.; et al.; Amino derivatives of phenyl alkyl thiophene as inhibitors of bone resorption. Structure-activity relationship. Arzneim-Forsch Drug Res 1998, 48, 8, 840.
【2】 Wierzbicki, M.; Sauveur, F.; Bonnet, J.; Brisset, M.; Tordjman, C. (ADIR et Cie.); Thiophene derivs., process for their preparation and pharmaceutical compsns. containing them. AU 9166901; EP 0429370; FR 2655043; JP 1991190872; US 5061704 .

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)	28328	3-(4-methylphenyl)propionic acid	1505-50-6	C₁₀H₁₂O₂	详情	详情
(II)	28329	3-(4-methylphenyl)propanoyl chloride		C₁₀H₁₁ClO	详情	详情
(III)	13297	Thiophene	110-02-1	C₄H₄S	详情	详情
(IV)	28330	3-(4-methylphenyl)-1-(2-thienyl)-1-propanone		C₁₄H₁₄OS	详情	详情
(V)	28331	2-[3-(4-methylphenyl)propyl]thiophene		C₁₄H₁₆S	详情	详情
(VI)	25549	4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione	4160-82-1	C₇H₁₀O₃	详情	详情
(VII)	28332	3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]-5-oxopentanoic acid		C₂₁H₂₆O₃S	详情	详情
(VIII)	28333	3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]pentanoic acid		C₂₁H₂₈O₂S	详情	详情
(IX)	24354	2,3-dimethoxy-4-(1-piperazinylmethyl)phenyl methyl ether		C₁₄H₂₂N₂O₃	详情	详情
(X)	28334	3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]-1-[4-(2,3,4-trimethoxybenzyl)-1-piperazinyl]-1-pentanone		C₃₅H₄₈N₂O₄S	详情	详情

Extended Information