8-(9-oxotricyclo[3.3.1.0(3,7)]non-3-yl)-1,3-dipropyl-3,7-dihydro-1H-purine-2,6-dione -Drug Synthesis Database

【结构式】

【分子编号】20545

【品名】8-(9-oxotricyclo[3.3.1.0(3,7)]non-3-yl)-1,3-dipropyl-3,7-dihydro-1H-purine-2,6-dione

【CA登记号】

【分子式】C₂₀H₂₆N₄O₃

【分子量】370.4516

【元素组成】C 64.85% H 7.07% N 15.12% O 12.96%

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：(V)

The oxidation of tricyclo[3.3.1.03,7]nonane-3-carboxylic acid methyl ester (I) with CrO3 in acetic anhydride/acetic acid gives a mixture of the 9-oxo and 6-oxo isomers (II), which is condensed with 5,6-diamino-1,3-dipropylpyrimidine-2,4(1H,3H)-dione (III) by means of LiOH, and after HPLC separation yields the 9-oxo isomer (IV) of the condensation product. The cyclization of (IV) by means of Ca(OH)2 affords the 1,3-dipropylxanthine derivative (V), which is finally reduced with LiBH4 to a mixture of isomers that is separated by HPLC yielding finally metabolite M1.

参考文献中间体

合成目标

【1】 Shimada, J.; Eguchi, T.; Yasuzawa, T.; Nakamura, A.; Horiguchi, A.; Mochida, K.; Suzuki, F.; Synthesis of rat metabolites of a adenosine A1 antagonist, KW-3902. Symp Med Chem 1996, Abst 1-P-24.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IIa)	20541	methyl 9-oxotricyclo[3.3.1.0(3,7)]nonane-3-carboxylate	C₁₁H₁₄O₃	详情	详情
(IIb)	20542	methyl 6-oxotricyclo[3.3.1.0(3,7)]nonane-3-carboxylate	C₁₁H₁₄O₃	详情	详情
M1	63837	8-(9-hydroxytricyclo[3.3.1.0~3,7~]non-3-yl)-1,3-dipropyl-3,7-dihydro-1H-purine-2,6-dione	C₂₀H₂₈N₄O₃	详情	详情
(I)	20540	methyl tricyclo[3.3.1.0(3,7)]nonane-3-carboxylate	C₁₁H₁₆O₂	详情	详情
(III)	14628	5,6-diamino-1,3-dipropyl-2,4(1H,3H)-pyrimidinedione	C₁₀H₁₈N₄O₂	详情	详情
(IV)	20544	N-(6-amino-2,4-dioxo-1,3-dipropyl-1,2,3,4-tetrahydro-5-pyrimidinyl)-9-oxotricyclo[3.3.1.0(3,7)]nonane-3-carboxamide	C₂₀H₂₈N₄O₄	详情	详情
(V)	20545	8-(9-oxotricyclo[3.3.1.0(3,7)]non-3-yl)-1,3-dipropyl-3,7-dihydro-1H-purine-2,6-dione	C₂₀H₂₆N₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The condensation of 9-oxotricyclo[3.3.1.03,7]nonane-3-carboxylic acid methyl ester (II) with 5,6-diamino-1-propylpyrimidine-2,4(1H,3H)-dione (VI) by means of LiOH gives the expected condensation product (VII), which by reduction with NaBH4 and HPLC separation yields the exo-hydroxy isomer (VIII). The condensation of (VIII) with bromoacetone (IX) by means of cesium carbonate affords compound (X), which is cyclized with Ca(OH)2 as before to give metabolite M3. Finally, this compound is reduced with NaBH4 to afford metabolite M2.

参考文献中间体

合成目标

【1】 Shimada, J.; Eguchi, T.; Yasuzawa, T.; Nakamura, A.; Horiguchi, A.; Mochida, K.; Suzuki, F.; Synthesis of rat metabolites of a adenosine A1 antagonist, KW-3902. Symp Med Chem 1996, Abst 1-P-24.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IIa)	20541	methyl 9-oxotricyclo[3.3.1.0(3,7)]nonane-3-carboxylate		C₁₁H₁₄O₃	详情	详情
M3	63838	8-(9-hydroxytricyclo[3.3.1.0~3,7~]non-3-yl)-1-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione		C₂₀H₂₆N₄O₄	详情	详情
M2	63839	1-(2-hydroxypropyl)-8-(9-hydroxytricyclo[3.3.1.0~3,7~]non-3-yl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione		C₂₀H₂₈N₄O₄	详情	详情
(V)	20545	8-(9-oxotricyclo[3.3.1.0(3,7)]non-3-yl)-1,3-dipropyl-3,7-dihydro-1H-purine-2,6-dione		C₂₀H₂₆N₄O₃	详情	详情
(VI)	20546	5,6-diamino-1-propyl-2,4(1H,3H)-pyrimidinedione		C₇H₁₂N₄O₂	详情	详情
(VII)	20547	N-(6-amino-2,4-dioxo-1-propyl-1,2,3,4-tetrahydro-5-pyrimidinyl)-9-oxotricyclo[3.3.1.0(3,7)]nonane-3-carboxamide		C₁₇H₂₂N₄O₄	详情	详情
(VIII)	20548	N-(6-amino-2,4-dioxo-1-propyl-1,2,3,4-tetrahydro-5-pyrimidinyl)-9-hydroxytricyclo[3.3.1.0(3,7)]nonane-3-carboxamide		C₁₇H₂₄N₄O₄	详情	详情
(IX)	20549	1-bromoacetone	598-31-2	C₃H₅BrO	详情	详情
(X)	20550	N-[6-amino-2,4-dioxo-3-(2-oxopropyl)-1-propyl-1,2,3,4-tetrahydro-5-pyrimidinyl]-9-hydroxytricyclo[3.3.1.0(3,7)]nonane-3-carboxamide		C₂₀H₂₈N₄O₅	详情	详情

Extended Information