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【结 构 式】

【分子编号】14678

【品名】(1S,2S,3S,4R)-3-allylbicyclo[2.2.1]hept-2-ylamine; (1S,2S,3S,4R)-3-allylbicyclo[2.2.1]heptan-2-amine

【CA登记号】

【 分 子 式 】C10H17N

【 分 子 量 】151.25172

【元素组成】C 79.41% H 11.33% N 9.26%

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:(XVIII)

The alkylation of bicyclo[2.2.1]heptan-2-one (XV) with allyl bromide and BuLi in THF gives exo-3-allylbicyclo[2.2.1]heptan-2-one (XVI), which by reaction with hydroxylamine is converted into the corresponding oxime (XVII). The reduction of (XVII) with LiAlH4 in THF yields 3exo-allylbicyclo[2.2.1]heptan-2endo-amine (XVIII), which is acylated with benzyloxycarbonylchloride by means of pyridine in dichloromethane to the carbamic ester (XIX). The epoxidation of (XIX) with m-chloroperbenzoic acid in dichloromethane affords the epoxide (XX), which by oxidation with HIO4 is converted into the aldehyde (XXI). The Wittig condensation of (XXI) with 4-carboxybutyl triphenylphosphonium bromide by means of NaH in DMSO, followed by methylation with CH2N2 affords 7-[3endo-(benzyloxycarbonylamino)bicyclo[2.2.1]hept-2exo-yl]-5(Z)-heptenoic acid methyl ester (XXII), which is deprotected with trifluoroacetic acid to the free amino ester (XXIII). The acylation of (XXIII) with benzenesulfonyl chloride as before gives the sulfonamide ester (XXIV), which is finally hydrolyzed with KOH in methanol - water to 7-[3endo-(phenylsulfonamido)bicyclo[2.2.1]hept-2exo-yl]-5(Z)-heptenoic acid (XIV) as a racemic mixture.

1 Watanabe, F.; Narisada, M.; Ohtani, M.; Hagishita, S.; Tsuri, T.; Seno, K.; Tsushima, T.; Kamata, S.; Kawada, K.; Haga, N. (Shionogi & Co. Ltd.); Bicyclic sulfonamide derivs. EP 0226346; GB 2184118; JP 1988139161; US 5043451; US 5043456 .
2 Narisada, M.; Uchida, K.; Otani, K.; Doteuchi, M.; Hanasaki, K.; Ohtani, M.; Hara, S.; Arita, H.; Watanabe, F.; Kakushi, H.; Synthesis and in vitro activity of various derivatives of a novel thromboxane receptor antagonist, (±)-5(Z)-7-[3-endo-[(phenylsulfonyl)aminobicyclo[2.2.1]hept-2-exo-yl] heptenoic acid. J Med Chem 1988, 31, 9, 1847-54.
3 Narisada, M.; Ohtani, M.; Watanabe, F.; et al.; Synthesis and in vitro effects on platelet and vascular smooth muscle of S-145, a novel thromboxane receptor antagonist. Advances in Prostaglandin, Thromboxane, and Leukotriene Research, Vol. 19. B. Samuelsson, P.Y.-K.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIV) 14674 (Z)-7-[(1R,2S,3S,4S)-3-[(phenylsulfonyl)amino]bicyclo[2.2.1]hept-2-yl]-5-heptenoic acid C20H27NO4S 详情 详情
(XV) 14675 (1S,4R)bicyclo[2.2.1]heptan-2-one 2630-41-3 C7H10O 详情 详情
(XVI) 14676 (1S,3S,4R)-3-allylbicyclo[2.2.1]heptan-2-one C10H14O 详情 详情
(XVII) 14677 (1S,3S,4R)-3-allylbicyclo[2.2.1]heptan-2-one oxime C10H15NO 详情 详情
(XVIII) 14678 (1S,2S,3S,4R)-3-allylbicyclo[2.2.1]hept-2-ylamine; (1S,2S,3S,4R)-3-allylbicyclo[2.2.1]heptan-2-amine C10H17N 详情 详情
(XIX) 14679 benzyl N-[(1S,2S,3S,4R)-3-allylbicyclo[2.2.1]hept-2-yl]carbamate C18H23NO2 详情 详情
(XX) 14680 benzyl N-[(1S,2S,3S,4R)-3-(2-oxiranylmethyl)bicyclo[2.2.1]hept-2-yl]carbamate C18H23NO3 详情 详情
(XXI) 14681 benzyl N-[(1S,2S,3S,4R)-3-(2-oxoethyl)bicyclo[2.2.1]hept-2-yl]carbamate C17H21NO3 详情 详情
(XXII) 14682 methyl (Z)-7-((1R,2S,3S,4S)-3-[[(benzyloxy)carbonyl]amino]bicyclo[2.2.1]hept-2-yl)-5-heptenoate C23H31NO4 详情 详情
(XXIII) 14683 methyl (Z)-7-[(1R,2S,3S,4S)-3-aminobicyclo[2.2.1]hept-2-yl]-5-heptenoate C15H25NO2 详情 详情
(XXIV) 14684 methyl (Z)-7-[(1R,2S,3S,4S)-3-[(phenylsulfonyl)amino]bicyclo[2.2.1]hept-2-yl]-5-heptenoate C21H29NO4S 详情 详情
Extended Information