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【结 构 式】

【分子编号】21753

【品名】ethyl 2-[(6-amino-9H-purin-9-yl)methyl]-2-bromocyclopropanecarboxylate

【CA登记号】

【 分 子 式 】C12H14BrN5O2

【 分 子 量 】340.17966

【元素组成】C 42.37% H 4.15% Br 23.49% N 20.59% O 9.41%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VI)

The addition of ethyl diazoacetate (II) to 2,3-dibromopropene (I) catalyzed by dirhodium tetraacetate in CH2Cl2 yielded a mixture of E- (III) and Z- (IV) cyclopropanes. Alkylation of adenine (V) with the mixture of bromoesters (III) and (IV) in the presence of either NaH in DMF at r.t. or K2CO3 at 80 C provided the diastereomeric (cyclopropylmethyl)adenines (VI). Elimination of HBr was carried out with potassium tert-butoxide in cold DMF or with NaH in THF to yield an unseparable mixture of Z- (VII) and E- (VIII) methylene cyclopropanes. Alternatively, simultaneous alkylation of adenine (V) and elimination of HBr to give (VII) + (VIII) was effected using K2CO3 in DMF at 100 C. Reduction of the ester groups of (VII) and (VIII) with DIBALH afforded a mixture of the racemic (Z) title compound (IX) and its its E-isomer (X). The unseparable mixture of (IX) and (X) was treated with dimethylformamide dimethylacetal in DMF to give the corresponding (dimethylamino)methylene derivatives that allowed a chromatographic separation. The desired racemic (Z)-isomer (XI) was further deprotected in methanolic ammonia to furnish racemic (IX) (1). Optical resolution was then achieved on treatment with adenosine deaminase, to produce the (Z)(S)-(+)-hypoxanthine derivative (XII) that was separated chromatographically from the unchanged (Z)(R)-(-)-isomer, the target compound.

1 Qiu, Y.-L.; et al.; (Z)- and (E)-2-((Hydroxymethyl)cyclopropylidene)methyladenine and -guanine. New nucleoside analogues with a broad-spectrum antiviral activity. J Med Chem 1998, 41, 1, 10.
2 Qiu, Y.-L.; Hempel, A.; Camerman, N.; Camerman, A.; Geiser, F.; Ptak, R.G.; Breitenbach, J.M.; Kira, T.; Li, L.; Gullen, E.; Cheng, Y.C.; Drach, J.C.; Zemlicka, J.; (R)-(-)- and (S)-(+)-synadenol: Synthesis, absolute configuration, and enantioselectivity of antiviral effect. J Med Chem 1998, 41, 26, 5257.
3 Zemilicka, J.; Qiu, Y.-L.; A new efficient synthesis of antiviral methylenecyclopropane analogs of purine nucleosides. Synthesis 1998, 10, 1447-1452.
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) 21748 2,3-dibromo-1-propene 513-31-5 C3H4Br2 详情 详情
(II) 21749 Diazoacetic acid ethyl ester; Diazoacetic acid ethyl ester C4H7N2O2 详情 详情
(III) 21750 ethyl (1S,2R)-2-bromo-2-(bromomethyl)cyclopropanecarboxylate C7H10Br2O2 详情 详情
(IV) 21751 ethyl (1S,2S)-2-bromo-2-(bromomethyl)cyclopropanecarboxylate C7H10Br2O2 详情 详情
(V) 10343 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine 73-24-5 C5H5N5 详情 详情
(VI) 21753 ethyl 2-[(6-amino-9H-purin-9-yl)methyl]-2-bromocyclopropanecarboxylate C12H14BrN5O2 详情 详情
(VII) 21754 ethyl 2-[(Z)-(6-amino-9H-purin-9-yl)methylidene]cyclopropanecarboxylate C12H13N5O2 详情 详情
(VIII) 21755 ethyl 2-[(E)-(6-amino-9H-purin-9-yl)methylidene]cyclopropanecarboxylate C12H13N5O2 详情 详情
(IX) 21756 [2-[(Z)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methanol C10H11N5O 详情 详情
(X) 21757 [2-[(E)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methanol C10H11N5O 详情 详情
(XI) 21758 N'-(9-[[2-(hydroxymethyl)cyclopropylidene]methyl]-9H-purin-6-yl)-N,N-dimethyliminoformamide C13H16N6O 详情 详情
(XII) 21759 9-[[(2S)-2-(hydroxymethyl)cyclopropylidene]methyl]-1,9-dihydro-6H-purin-6-one C10H10N4O2 详情 详情
Extended Information