tert-butyl 3-(4-formylphenyl)-4,5-dihydro-5-isoxazolecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】45674

【品名】tert-butyl 3-(4-formylphenyl)-4,5-dihydro-5-isoxazolecarboxylate

【CA登记号】

【分子式】C₁₅H₁₇NO₄

【分子量】275.30432

【元素组成】C 65.44% H 6.22% N 5.09% O 23.25%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

Terephthaldehyde mono-diethyl acetal (I) was treated with hydroxylamine.HCl and Et3N to give the corresponding oxime (II). The nitrile oxide resulting from the treatment of oxime (II) with sodium hypochlorite was subjected to a dipolar cycloaddition with tert-butyl acrylate (III), yielding the isoxazoline (IV). Subsequent hydrolysis of acetal (IV) employing an acidic ion-exchange resin provided the intermediate isoxazoline aldehyde (V).

参考文献中间体

合成目标

【1】 Slee, D.H.; et al.; Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors antiinflammatory activity. J Med Chem 2001, 44, 13, 2094.
【2】 Kondo, H.; Inoue, Y.; Jones, T.K.; Ripka, W.C.; Yu, J.; Raheja, R.K.; Nguyen, T.N.; Slee, D.H. (NV Organon; Ontogen Corp.); Substd. thiazoles for treatment of human diseases involving modulators of P-, L- and E-selectin. WO 0033836; WO 0034255 .

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)	45671	Terephthaldehyde mono(diethyl acetal); Terephthalaldehyde mono(diethyl acetal); 4-(Diethoxymethyl)benzaldehyde	81172-89-6	C₁₂H₁₆O₃	详情	详情
(II)	45672	4-(diethoxymethyl)benzaldehyde oxime		C₁₂H₁₇NO₃	详情	详情
(III)	12760	tert-butyl acrylate	1663-39-4	C₇H₁₂O₂	详情	详情
(IV)	45673	tert-butyl 3-[4-(diethoxymethyl)phenyl]-4,5-dihydro-5-isoxazolecarboxylate		C₁₉H₂₇NO₅	详情	详情
(V)	45674	tert-butyl 3-(4-formylphenyl)-4,5-dihydro-5-isoxazolecarboxylate		C₁₅H₁₇NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Heck reaction of 4,4'-dibromobenzil (VI) with tert-butyl acrylate (III) in the presence of palladium diacetate and tri(o-tolyl)phosphine afforded the arylacrylate ester (VII), which was subsequently condensed with the acrylamide (X) (prepared from acryloyl chloride (VIII) and hexadecylamine (IX)), to furnish adduct (XI). The condensation of diketone (XI) with aldehyde (V) in the presence of ammonium acetate in HOAc produced imidazole (XII). The tert-butyl ester groups of (XII) were finally cleaved by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Slee, D.H.; et al.; Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors antiinflammatory activity. J Med Chem 2001, 44, 13, 2094.
【2】 Kondo, H.; Inoue, Y.; Jones, T.K.; Ripka, W.C.; Yu, J.; Raheja, R.K.; Nguyen, T.N.; Slee, D.H. (NV Organon; Ontogen Corp.); Substd. thiazoles for treatment of human diseases involving modulators of P-, L- and E-selectin. WO 0033836; WO 0034255 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	12760	tert-butyl acrylate	1663-39-4	C₇H₁₂O₂	详情	详情
(V)	45678	tert-butyl (E)-3-[4-(2-[4-[(E)-3-(hexadecylamino)-3-oxo-1-propenyl]phenyl]-2-oxoacetyl)phenyl]-2-propenoate		C₄₀H₅₅NO₅	详情	详情
(VI)	38940	1,2-bis(4-bromophenyl)-1,2-ethanedione	35578-47-3	C₁₄H₈Br₂O₂	详情	详情
(VII)	45675	tert-butyl (E)-3-[4-[2-(4-bromophenyl)-2-oxoacetyl]phenyl]-2-propenoate		C₂₁H₁₉BrO₄	详情	详情
(VIII)	11577	Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride	814-68-6	C₃H₃ClO	详情	详情
(IX)	45676	1-Aminohexadecane; n-Hexadecylamine; Palmitylamine; Cetylamine; hexadecylamine; 1-hexadecanamine	143-27-1	C₁₆H₃₅N	详情	详情
(X)	45677	N-hexadecylacrylamide		C₁₉H₃₇NO	详情	详情
(XI)	45674	tert-butyl 3-(4-formylphenyl)-4,5-dihydro-5-isoxazolecarboxylate		C₁₅H₁₇NO₄	详情	详情
(XII)	45679	tert-butyl 3-[4-(4-[4-[(E)-3-(tert-butoxy)-3-oxo-1-propenyl]phenyl]-5-[4-[(E)-3-(hexadecylamino)-3-oxo-1-propenyl]phenyl]-1H-imidazol-2-yl)phenyl]-4,5-dihydro-5-isoxazolecarboxylate		C₅₅H₇₂N₄O₆	详情	详情

Extended Information