3-[1-(3-aminophenyl)propyl]-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one -Drug Synthesis Database

【结构式】

【分子编号】32882

【品名】3-[1-(3-aminophenyl)propyl]-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one

【CA登记号】

【分子式】C₂₅H₃₁NO₃

【分子量】393.52608

【元素组成】C 76.3% H 7.94% N 3.56% O 12.2%

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：(VII)

A new synthesis of PNU-140690 has been developed: The condensation of 1-phenyl-3-hexanone (I) with methyl acetoacetate (II) by means of NaH in THF, followed by cyclization gives the hydroxypyrone (III), which by condensation with 3-nitrobenzaldehyde (IV) by means of AlCl3 in THF yields the benzylidene-pyrone (V). The alkylation of (V) with Et3Al, CuBr-Me2S in THF affords intermediate (VI), which is reduced at the nitro group with H2 over Pd/C in methanol giving the racemic amine (VII). The optical resolution of the N-benzyloxycarbonyl derivative of (VII) with chiral HPLC yielded the desired (R,R)-enantiomer (VIII), which was finally sulfonated with 5-(trifluoromethyl)pyridine-2-sulfonyl chloride (IX) in pyridine/dichloromethane.

参考文献中间体

合成目标

【1】 Turner, S.R.; Strohbach, J.W.; Tommasi, R.A.; Aristoff, P.A.; Johnson, P.D.; Skulnick, H.I.; Dolak, L.A.; Seest, E.P.; Tomich, P.K.; Bohanon, M.J.; Horng, M.M.; Lynn, J.C.; Chong, K.T.; Hinshaw, R.R.; Watenpaugh, K.D.; Janakiraman, M.N.; Thaisrivongs, S.; Tipranavir (PNU-140690): A potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. J Med Chem 1998, 41, 18, 3467.

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)	17233	1-phenyl-3-hexanone		C₁₂H₁₆O	详情	详情
(II)	11791	methyl 3-oxobutanoate; Methyl acetoacetate	105-45-3	C₅H₈O₃	详情	详情
(III)	32879	4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one		C₁₆H₂₀O₃	详情	详情
(IV)	12646	3-Nitrobenzaldehyde	99-61-6	C₇H₅NO₃	详情	详情
(V)	32880	3-[(Z)-(3-nitrophenyl)methylidene]-6-phenethyl-6-propyldihydro-2H-pyran-2,4-dione		C₂₃H₂₃NO₅	详情	详情
(VI)	32881	4-hydroxy-3-[1-(3-nitrophenyl)propyl]-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one		C₂₅H₂₉NO₅	详情	详情
(VII)	32882	3-[1-(3-aminophenyl)propyl]-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one		C₂₅H₃₁NO₃	详情	详情
(VIII)	17236	(6R)-3-[(1R)-1-(3-aminophenyl)propyl]-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one		C₂₅H₃₁NO₃	详情	详情
(IX)	17237	5-(trifluoromethyl)-2-pyridinesulfonyl chloride		C₆H₃ClF₃NO₂S	详情	详情

Extended Information