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【结 构 式】 
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【分子编号】43559 【品名】1-cyclopentyl-7-(methylsulfanyl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one 【CA登记号】 |
【 分 子 式 】C12H16N4OS 【 分 子 量 】264.3514 【元素组成】C 54.52% H 6.1% N 21.19% O 6.05% S 12.13% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Condensation of S-methylisothiourea (I) and cyano acetate derivative (II) by means of NaOMe in MeOH affords pyrimidine derivative (III), whose hydroxy group is converted into chloro by means of refluxing POCl3, yielding derivative (IV). Alkylation of (IV) with cyclopentylamine (V) and Et3N in CH2Cl2 provides derivative (VI), whose nitrile group is then reduced by means of LiAlH4 in THF to afford aminomethyl compound (VII). Treatment of (VII) with 1,1-carbonyldiimidazole (CDI) in refluxing THF gives pyrimidopyrimidinone (VIII), whose methylsulfanyl group is oxidized with 3-phenyl-2-(phenylsulfonyl)oxaziridine (IX) in CHCl3 to afford methyl sulfoxide derivative (X). Displacement of the methyl sulfoxide group of (X) with substituted aniline (XI) in TFA/acetonitrile yields 3,4-dihydropyrimidopyrimidinone (XII), which is finally oxidized by means of KOtBu in THF or DMSO.
| 【1】 Kramer, J.B.; et al.; Synthesis and biological activity of a novel series of pyrimidopyrimidinones as inhibitors of cyclin-dependent kinases. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 40. |
| 【2】 Dobrusin, E.M.; Showalter, H.D.H.; Schroeder, M.C.; Toogood, P.; Kramer, J.B.; Trumpp-Kallmeyer, S.A.; Hamby, J.M. (Pfizer Inc.); Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation. WO 9961444 . |
| 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) | 43041 | ethyl (Z)-2-cyano-3-ethoxy-2-propenoate | 94-05-3 | C8H11NO3 | 详情 | 详情 |
| (IIb) | 43563 | ethyl (E)-2-cyano-3-ethoxy-2-propenoate；(E)-ethyl 2-cyano-3-ethoxyacrylate | 94-05-3 | C8H11NO3 | 详情 | 详情 |
| (I) | 10272 | [[Amino(imino)methyl]sulfanyl]methane | 2986-19-8 | C2H6N2S | 详情 | 详情 |
| (III) | 43555 | 4-hydroxy-2-(methylsulfanyl)-5-pyrimidinecarbonitrile | C6H5N3OS | 详情 | 详情 | |
| (IV) | 43556 | 4-chloro-2-(methylsulfanyl)-5-pyrimidinecarbonitrile | C6H4ClN3S | 详情 | 详情 | |
| (V) | 28850 | cyclopentanamine | 1003-03-8 | C5H11N | 详情 | 详情 |
| (VI) | 43557 | 4-(cyclopentylamino)-2-(methylsulfanyl)-5-pyrimidinecarbonitrile | C11H14N4S | 详情 | 详情 | |
| (VII) | 43558 | N-[5-(aminomethyl)-2-(methylsulfanyl)-4-pyrimidinyl]-N-cyclopentylamine; 5-(aminomethyl)-N-cyclopentyl-2-(methylsulfanyl)-4-pyrimidinamine | C11H18N4S | 详情 | 详情 | |
| (VIII) | 43559 | 1-cyclopentyl-7-(methylsulfanyl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one | C12H16N4OS | 详情 | 详情 | |
| (IX) | 31834 | 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine;2-(Phenylsulfonyl)-3-phenyloxaziridine;2-Benzenesulfonyl-3-phenyloxaziridine;3-Phenyl-2-phenylsulfonyloxaziridine;3-Phenyl-N-phenylsulfonyloxaziridine;N-(Phenylsulfonyl)phenyloxaziridine;N-Benzenesulfonyl-3-phenyloxaziridine | 63160-13-4 | C13H11NO3S | 详情 | 详情 |
| (X) | 43560 | 1-cyclopentyl-7-(methylsulfinyl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one | C12H16N4O2S | 详情 | 详情 | |
| (XI) | 43561 | 1-(4-aminophenyl)-4-piperidinol | C11H16N2O | 详情 | 详情 | |
| (XII) | 43562 | 1-cyclopentyl-7-[4-(4-hydroxy-1-piperidinyl)anilino]-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one | C22H28N6O2 | 详情 | 详情 |