5,6-diamino-1-propyl-2,4(1H,3H)-pyrimidinedione -Drug Synthesis Database

【结构式】

【分子编号】20546

【品名】5,6-diamino-1-propyl-2,4(1H,3H)-pyrimidinedione

【CA登记号】

【分子式】C₇H₁₂N₄O₂

【分子量】184.19804

【元素组成】C 45.64% H 6.57% N 30.42% O 17.37%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XIII)

The reaction of N-propylurea (V) with cyanacetic acid (VI) in hot acetic anhydride gives N-propyl-N'-cyanacetylurea (VII), which is nitrosated with NaNO2 - HCl yielding the isonitroso derivative (VIII). The reduction and simultaneous formylation of (VIII) with Zn in formic acid affords the formylamino compound (IX), which is cyclized by treatment with NaOH to give 6-amino-5-formylamino-1-propylpyrimidine-2,4-dione (X). Finally, this compound is cyclized by treatment with refluxing formic acid. The cyclization of (VII) with NaOH in hot water gives 6-amino-1-propylpyrimidine-2,4-dione (XI), which is nitrosated with NaNO2 - HCl as usual yielding 6-amino-nitroso-1-propylpyrimidine-2,4-dione (XII). The reduction of (XII) with H2 over Pt in DMF affords 5,6-diamino-1-propylpyrimidine-2,4-dione (XIII), which is finally formylated with refluxing formic acid to (X). This compound can also be finally cyclized by treatment with NaOH in refluxing water.

参考文献中间体

合成目标

【1】 Ohtsuka, Y.; Oxazolopyrimidines. VI. Formation of 3-substituted xanthines via 7-(6H)-iminooxazolopyrimidines. Bull Chem Soc Jpn 1973, 46, 2, 506-509.
【2】 Kjellin, P.G.; Persson, C.G.A. (Draco Läkemedel AB); Method and pharmaceutical preparation for treating chronic obstructive airway disease and cardiac disease, and intermediates for the preparation of therapeutically active xanthine derivs.. EP 0011609 .
【3】 Sneddon, J.M.; Castaner, J.; Blancafort, P.; Serradell, M.N.; Enprofylline. Drugs Fut 1982, 7, 9, 623.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	37133	N-propylurea		C₄H₁₀N₂O	详情	详情
(VI)	12591	Cyanoacetic Acid; 2-Cyanoacetic acid	372-09-8	C₃H₃NO₂	详情	详情
(VII)	37134	N-(2-cyanoacetyl)-N'-propylurea		C₇H₁₁N₃O₂	详情	详情
(VIII)	37135	N-[2-cyano-2-(hydroxyimino)acetyl]-N'-propylurea		C₇H₁₀N₄O₃	详情	详情
(IX)	37136	N-[2-cyano-2-(formylamino)acetyl]-N'-propylurea		C₈H₁₂N₄O₃	详情	详情
(X)	37137	6-amino-2,4-dioxo-1-propyl-1,2,3,4-tetrahydro-5-pyrimidinylformamide		C₈H₁₂N₄O₃	详情	详情
(XI)	37138	6-amino-1-propyl-2,4(1H,3H)-pyrimidinedione		C₇H₁₁N₃O₂	详情	详情
(XII)	37139	6-amino-5-nitroso-1-propyl-2,4(1H,3H)-pyrimidinedione		C₇H₁₀N₄O₃	详情	详情
(XIII)	20546	5,6-diamino-1-propyl-2,4(1H,3H)-pyrimidinedione		C₇H₁₂N₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

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

合成路线3

该中间体在本合成路线中的序号：(I)

The cyclization of 5,6-diamino-1-propylpyrimidine-2,4(1H,3H)-dione (I) with 4-bromobenzoic acid (II) by means of EDC and HOBT in DMF gives 8-(4-bromophenyl)-3-propylxanthine (III), which is treated with P2S5 in refluxing pyridine to yield the 6-thioxanthine (IV). The reaction of (IV) with Me-I and NaOH in ethanol affords the methylsulfanylpurin-2-one (V), which is treated with ethanolamine (VI) in DMSO at 150 C to provide the 2-hydroxyethylamino derivative (VII). Finally, this compound is cyclized by means of SOCl2 in refluxing chloroform to provide the target imidazopurine.

参考文献中间体

合成目标

【1】 Tsumuki, H.; Saki, M.; Nonaka, H.; Ichimura, M.; Shimada, J.; Suzuki, F.; Ichikawa, S.; Kosaka, N. (Kyowa Hakko Kogyo Co., Ltd.); Fused purine derivs.. EP 0884318; US 6306847; WO 9815555 .

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)	20546	5,6-diamino-1-propyl-2,4(1H,3H)-pyrimidinedione		C₇H₁₂N₄O₂	详情	详情
(II)	60207	4-bromo-1,3-cyclohexadiene-1-carboxylic acid		C₇H₇BrO₂	详情	详情
(III)	60208	8-(4-bromophenyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione		C₁₄H₁₃BrN₄O₂	详情	详情
(IV)	60209	8-(4-bromophenyl)-3-propyl-6-thioxo-1,3,6,7-tetrahydro-2H-purin-2-one		C₁₄H₁₃BrN₄OS	详情	详情
(V)	60210	8-(4-bromophenyl)-6-(methylsulfanyl)-3-propyl-3,7-dihydro-2H-purin-2-one		C₁₅H₁₅BrN₄OS	详情	详情
(VI)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(VII)	60211	8-(4-bromophenyl)-6-[(2-hydroxyethyl)amino]-3-propyl-3,7-dihydro-2H-purin-2-one		C₁₆H₁₈BrN₅O₂	详情	详情

Extended Information