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【结 构 式】

【分子编号】19231

【品名】9-[(2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-9H-purin-6-amine; 9-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-9H-purin-6-ylamine

【CA登记号】

【 分 子 式 】C13H19N5O2

【 分 子 量 】277.32636

【元素组成】C 56.3% H 6.91% N 25.25% O 11.54%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VI)

1) The protection of isobutyl D-(+)-lactate (I) with dihydropyran (DHP)/HCl in DMF gives the tetrahydropyranyloxy derivative (II), which is reduced with bis(2-methoxyethoxy)aluminum hydride in refluxing ether/ toluene yielding 2(R)-(tetrahydropyranyloxy)-1-propanol (III). The tosylation of (III) with tosyl chloride as usual affords the expected tosylate (VI), which is condensed with adenine (V) by means of Cs2CO3 in hot DMF, affording 9-[2(R)-(tetrahydropyranyloxy)propyl]adenine (VI). The deprotection of (VI) with sulfuric acid affords 9-[2(R)-hydroxypropyl]adenine (VII), which is N-benzoylated with benzoyl chloride/chlorotrimethylsilane in pyridine to give the benzamide (VIII), which is condensed with tosyl-oxymethylphosphonic acid diisopropyl ester (IX) by means of NaH in DMF to yield 9-[2(R)-(diisopropoxyphosphorylmethoxy)propyl]adenine (X). Finally, this compound is hydrolyzed by means of bromotrimethylsilane in acetonotrile.

1 Masojídková, M.; Holý, A.; Synthesis of enantiomeric N-(2-phosphonomethoxypropyl) derivatives of purine and pyrimidine bases. I. The stepwise approach. Coll Czech Chem Commun 1995, 60, 7, 1196.
2 Sorbera, L.A.; Castañer, J.; (R)-PMPA and Bis(POC)PMPA. Drugs Fut 1998, 23, 12, 1279.
3 Holy, A.; Dvorakova, H.; DeClercq, E.D.A.; Balzarini, J.M.R. (Gilead Sciences Inc.; Stichting Rega Vzw); Antiretroviral enantiomeric nucleotide analogs. EP 0654037; JP 1996503927; US 6057305; WO 9403467 .
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) 19226 isobutyl (2R)-2-hydroxypropanoate 61597-96-4 C7H14O3 详情 详情
(II) 19227 isobutyl (2R)-2-(tetrahydro-2H-pyran-2-yloxy)propanoate C12H22O4 详情 详情
(III) 19228 (2S)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanol 76946-21-9 C8H16O3 详情 详情
(IV) 19229 (2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl 4-methylbenzenesulfonate C15H22O5S 详情 详情
(V) 10343 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine 73-24-5 C5H5N5 详情 详情
(VI) 19231 9-[(2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-9H-purin-6-amine; 9-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-9H-purin-6-ylamine C13H19N5O2 详情 详情
(VII) 19232 (2S)-1-(6-amino-9H-purin-9-yl)-2-propanol C8H11N5O 详情 详情
(VIII) 19233 N-[9-[(2S)-2-hydroxypropyl]-9H-purin-6-yl]benzamide C15H15N5O2 详情 详情
(IX) 19234 (diisopropoxyphosphoryl)methyl 4-methylbenzenesulfonate C14H23O6PS 详情 详情
(X) 19235 diisopropyl [[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy]methylphosphonate C15H26N5O4P 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VI)

 

1 Holy A, Dvorakovs H, Declercq ED, et al. Preparation of antiretroviral enantiomeric nucleotide analogs. WO 9403467
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) 66830 (S)-ethyl 2-hydroxypropanoate   C5H10O3 详情 详情
(II) 66831 (2S)-ethyl 2-((tetrahydro-2H-pyran-2-yl)oxy)propanoate 73208-70-5 C10H18O4 详情 详情
(III) 19228 (2S)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanol 76946-21-9 C8H16O3 详情 详情
(IV) 19229 (2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl 4-methylbenzenesulfonate C15H22O5S 详情 详情
(V) 10343 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine 73-24-5 C5H5N5 详情 详情
(VI) 19231 9-[(2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-9H-purin-6-amine; 9-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-9H-purin-6-ylamine C13H19N5O2 详情 详情
(VII) 19232 (2S)-1-(6-amino-9H-purin-9-yl)-2-propanol C8H11N5O 详情 详情
(VIII) 19233 N-[9-[(2S)-2-hydroxypropyl]-9H-purin-6-yl]benzamide C15H15N5O2 详情 详情
(IX) 19234 (diisopropoxyphosphoryl)methyl 4-methylbenzenesulfonate C14H23O6PS 详情 详情
(X) 19246 diethyl [[(1S)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy]methylphosphonate C13H22N5O4P 详情 详情
Extended Information