1-[1,1'-biphenyl]-4-yl-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】36916

【品名】1-[1,1'-biphenyl]-4-yl-1-ethanone

【CA登记号】92-91-1

【分子式】C₁₄H₁₂O

【分子量】196.24868

【元素组成】C 85.68% H 6.16% O 8.15%

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：(XI)

This compound has been obtained by two related ways: 1) The condensation of 4-acetylbiphenyl oxime (I) with 2-(2-bromoethoxy)tetrahydropyran (II) by means of K2CO3 in hot dimethylacetamide gives the oxime derivative (III), which is treated with TsOH in methanol yielding 4-acetylbiphenyl O-(2-hydroxyethyl)oxime (IV). The condensation of (IV) with 5-(4-hydroxybenzyl)-3-tritylthiazolidine-2,4-dione (V) by means of diethyl azodicarboxylate (DEAD) and PPh3 in THF affords (VI), the trityl derivative of the target compound, which is finally treated with hot aqueous ethanol to eliminate the trityl group. 2) The condensation of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione (VIII) with N-(2-hydroxyethoxy)phthalimide (VII) by means DEAD gives the adduct (IX), which is treated with hydrazine to eliminate the phthalimido group yielding the substituted hydroxylamine (X). Finally, this compound is condensed with 4-acetylbiphenyl (XI) by means of TEA.

参考文献中间体

合成目标

【1】 Yanagisawa, H.; Fujita, T.; Fujimoto, K.; Yoshioka, T.; Wada, K.; Oguchi, M.; Fujiwara, T.; Horikoshi, H. (Sankyo Co., Ltd.); Oxime derivs., their preparation and their therapeutic use. CA 2159938; EP 0708098; JP 1997048779; US 5703096; US 5780490; US 5972959 .
【2】 Isobe, A.; Fujita, S.; Fujiwara, T.; Yanagisawa, H.; Takamura, M.; Yamada, E.; Hagisawa, Y.; Yachi, M.; Novel oximes having 5-benzyl-2,4-thiazolidinedione as antihyperglycemic agents: Synthesis and structure-activity relationship. Bioorg Med Chem Lett 2000, 10, 4, 373.

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)	36912	1-[1,1'-biphenyl]-4-yl-1-ethanone oxime		C₁₄H₁₃NO	详情	详情
(II)	26934	2-bromoethyl tetrahydro-2H-pyran-2-yl ether		C₇H₁₃BrO₂	详情	详情
(III)	36913	1-[1,1'-biphenyl]-4-yl-1-ethanone O-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]oxime		C₂₁H₂₅NO₃	详情	详情
(IV)	36914	1-[1,1'-biphenyl]-4-yl-1-ethanone O-(2-hydroxyethyl)oxime		C₁₆H₁₇NO₂	详情	详情
(V)	18803	5-(4-hydroxybenzyl)-3-trityl-1,3-thiazolidine-2,4-dione		C₂₉H₂₃NO₃S	详情	详情
(VI)	36915	5-[4-[2-([[(E)-1-[1,1'-biphenyl]-4-ylethylidene]amino]oxy)ethoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione		C₄₅H₃₈N₂O₄S	详情	详情
(VII)	36908	2-(2-hydroxyethoxy)-1H-isoindole-1,3(2H)-dione		C₁₀H₉NO₄	详情	详情
(VIII)	26462	5-(4-hydroxybenzyl)-1,3-thiazolidine-2,4-dione	74772-78-4	C₁₀H₉NO₃S	详情	详情
(IX)	36909	2-(2-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]ethoxy)-1H-isoindole-1,3(2H)-dione		C₂₀H₁₆N₂O₆S	详情	详情
(X)	36910	5-[4-[2-(aminooxy)ethoxy]benzyl]-1,3-thiazolidine-2,4-dione		C₁₂H₁₄N₂O₄S	详情	详情
(XI)	36916	1-[1,1'-biphenyl]-4-yl-1-ethanone	92-91-1	C₁₄H₁₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation between 4-acetylbiphenyl (I) and 3-(trifluoromethyl)phenyl hydrazine (II) provided the corresponding hydrazone (III). Subsequent Vilsmeier-Haack reaction of (III) with POCl3 and DMF afforded the pyrazole aldehyde (IV). This was subjected to a Knoevenagel condensation with malonic acid to give the pyrazolylacrylic acid (V). Treatment of (V) with sulfur and ammonium hydroxide under Willgerodt-Kindler conditions led to the pyrazolylacetamide derivative (VI), which was further hydrolyzed to carboxylic acid (VII) using H2SO4 in aqueous HOAc. After conversion of (VII) to the corresponding acid chloride (VIII), condensation with dimethylamine in CH2Cl2 gave the title amide.

参考文献中间体

合成目标

【1】 Bebernitz, G.R.; et al.; The effect of 1,3-diaryl-[1H]-pyrazole-4-acetamides on glucose utilization in ob/ob mice. J Med Chem 2001, 44, 16, 2601.

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)	36916	1-[1,1'-biphenyl]-4-yl-1-ethanone	92-91-1	C₁₄H₁₂O	详情	详情
(II)	44088	1-[3-(trifluoromethyl)phenyl]hydrazine	368-78-5	C₇H₇F₃N₂	详情	详情
(III)	51028	1-[1,1'-biphenyl]-4-yl-1-ethanone N-[3-(trifluoromethyl)phenyl]hydrazone		C₂₁H₁₇F₃N₂	详情	详情
(IV)	51029	3-[1,1'-biphenyl]-4-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-4-carbaldehyde		C₂₃H₁₅F₃N₂O	详情	详情
(V)	51030	(E)-3-[3-[1,1'-biphenyl]-4-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]-2-propenoic acid		C₂₅H₁₇F₃N₂O₂	详情	详情
(VI)	51031	2-[3-[1,1'-biphenyl]-4-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]acetamide		C₂₄H₁₈F₃N₃O	详情	详情
(VII)	51032	2-[3-[1,1'-biphenyl]-4-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]acetic acid		C₂₄H₁₇F₃N₂O₂	详情	详情
(VIII)	51033	2-[3-[1,1'-biphenyl]-4-yl-1-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]acetyl chloride		C₂₄H₁₆ClF₃N₂O	详情	详情

Extended Information