2,2-diphenylacetic acid -Drug Synthesis Database

【结构式】

【分子编号】19827

【品名】2,2-diphenylacetic acid

【CA登记号】117-34-0

【分子式】C₁₄H₁₂O₂

【分子量】212.24808

【元素组成】C 79.23% H 5.7% O 15.08%

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：(II)

The reaction of 3-phenacyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6(S)-carboxylic acid methyl ester (I) with 2,2-diphenylacetic acid (II) gives 5-(2,2-diphenylacetyl)-3-phenacyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6(S)-carboxylic acid methyl ester (III), which is condensed with 3,5-dibromobenzyl bromide (IV) in acetic acid yielding the corresponding 1-(3,5-dibromobenzyl) derivative (V). The hydrolysis of the ester group of (V) with NaOH affords the expected free acid (VI), which is condensed with L-proline tert-butyl ester (VII) giving the corresponding N-substituted L-proline ester (VIII). Finall this compound is coupled with phenylboronic acid (IX), catalized with palladium tetrakis(triphenylphosphine) complex.

参考文献中间体

合成目标

【1】 Kim, D.; et al.; Non-peptide ligands of the human C5a receptor: Structure-activity relationship of a series of tetrahydroimidazopyridines. 213th ACS Natl Meet (April 13-17, San Francisco) 1997, Abst MEDI 088.

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)	19826	methyl (6S)-3-(2-oxo-2-phenylethyl)-3a,4,5,6,7,7a-hexahydro-3H-imidazo[4,5-c]pyridine-6-carboxylate		C₁₆H₁₉N₃O₃	详情	详情
(II)	19827	2,2-diphenylacetic acid	117-34-0	C₁₄H₁₂O₂	详情	详情
(III)	19828	methyl (6S)-5-(2,2-diphenylacetyl)-3-(2-oxo-2-phenylethyl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylate		C₃₀H₂₇N₃O₄	详情	详情
(IV)	19829	1,3-dibromo-5-(bromomethyl)benzene	56908-88-4	C₇H₅Br₃	详情	详情
(V)	19830	methyl (6S)-1-(3,5-dibromobenzyl)-5-(2,2-diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylate		C₂₉H₂₅Br₂N₃O₃	详情	详情
(VI)	19831	(6S)-1-(3,5-dibromobenzyl)-5-(2,2-diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid		C₂₈H₂₃Br₂N₃O₃	详情	详情
(VII)	19832	tert-butyl (2S)-2-pyrrolidinecarboxylate		C₉H₁₇NO₂	详情	详情
(VIII)	19833	tert-butyl (2S)-1-[[(6S)-1-(3,5-dibromobenzyl)-5-(2,2-diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-6-yl]carbonyl]-2-pyrrolidinecarboxylate		C₃₇H₃₈Br₂N₄O₄	详情	详情
(IX)	16593	Phenylboronic acid；Benzeneboronic acid;Phenylboron dihydroxide	98-80-6	C₆H₇BO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Treatment of 2,2-diphenylacetic acid (I) with diphenyl phosphoryl azide (DPPA) yielded acyl azide (II). Then, Curtius rearrangement of (II) in boiling toluene produced the intermediate isocyanate (III), which was coupled with 1-benzyl-4-piperidinol (IV) to afford the corresponding carbamate (V). Subsequent N-debenzylation of (V) was achieved by reaction with 1-chloroethyl chloroformate in refluxing 1,2-dichloroethane, followed by methanolysis to give (VI). Reductive alkylation of (VI) with aldehyde (VII) in the presence of sodium triacetoxyborohydride furnished the substituted benzyl piperidine (VIII). The N-Boc protecting group of (VIII) was finally removed with ethanolic HCl to provide the title compound.

参考文献中间体

合成目标

【1】 Naito, R.; Takeuchi, M.; Morihira, K.; Hayakawa, M.; Ikeda, K.; Shibanuma, T.; Isomura, Y.; Selective muscarinic antagonists. I. Synthesis and. Chem Pharm Bull 1998, 46, 8, 1274.

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)	19827	2,2-diphenylacetic acid	117-34-0	C₁₄H₁₂O₂	详情	详情
(II)	23302	2,2-diphenylacetyl azide		C₁₄H₁₁N₃O	详情	详情
(III)	23303	1-[isocyanato(phenyl)methyl]benzene; benzhydryl isocyanate		C₁₄H₁₁NO	详情	详情
(IV)	23304	1-benzyl-4-piperidinol; 1-benzyl-4-hydroxypiperidine; N-Benzyl-4-hydroxypiperidine; 1-(benzyl)-4-piperidinol	4727-72-4	C₁₂H₁₇NO	详情	详情
(V)	23305	1-benzyl-4-piperidinyl benzhydrylcarbamate		C₂₆H₂₈N₂O₂	详情	详情
(VI)	23306	4-piperidinyl benzhydrylcarbamate		C₁₉H₂₂N₂O₂	详情	详情
(VII)	23307	tert-butyl 4-formylphenyl(methyl)carbamate		C₁₃H₁₇NO₃	详情	详情
(VIII)	23308	1-[4-[(tert-butoxycarbonyl)(methyl)amino]benzyl]-4-piperidinyl benzhydrylcarbamate		C₃₂H₃₉N₃O₄	详情	详情

Extended Information