2-oxo-2-(3,4,5-trimethoxyphenyl)acetic acid -Drug Synthesis Database

【结构式】

【分子编号】30046

【品名】2-oxo-2-(3,4,5-trimethoxyphenyl)acetic acid

【CA登记号】

【分子式】C₁₁H₁₂O₆

【分子量】240.21268

【元素组成】C 55% H 5.04% O 39.96%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(X)

Condensation of 1,3-acetonedicarboxylic acid (I) with pyridine-4-carboxaldehyde (II) and subsequent acid decarboxylation produced 1,5-dipyridylpentadienone (III), which was reduced to the saturated ketone (IV) by transfer hydrogenation using formic acid and Pd/C. Condensation of (IV) with benzyl amine (V) in benzene with azeotropical removal of water, followed by reduction of the intermediate imine with NaBH4 gave rise to the secondary amine (VI). Coupling of (VI) with N-Boc-N-methyl-L-4-chlorophenylalanine (VII) in the presence of EDC afforded amide (VIII). After Boc deprotection of (VIII) with trifluoroacetic acid, the resulting amine (IX) was coupled with 3,4,5-trimethoxybenzoylformic acid (X) to furnish the title compound.

参考文献中间体

合成目标

【1】 Zelle, R.E.; Harding, M.W. (Vertex Pharmaceuticals Inc.); Novel amino acid derivs. with improved multi-drug resistance activity. EP 0797567; JP 1998509151; US 5543423; WO 9615101 .
【2】 Zelle, R.E. (Vertex Pharmaceuticals Inc.); Methods and compsns. for stimulating neurite growth using cpds. with affinity for FKBP2 in combination with neurotrophic factors. WO 9820891 .

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)	15530	1,3-Acetonedicarboxylic Acid; 3-Oxopentanedioic acid；3-oxoglutaric acid	542-05-2	C₅H₆O₅	详情	详情
(II)	17203	4-Pyridinecarboxaldehyde; isonicotinaldehyde	872-85-5	C₆H₅NO	详情	详情
(III)	30040	(1E,4E)-1,5-di(4-pyridinyl)-1,4-pentadien-3-one		C₁₅H₁₂N₂O	详情	详情
(IV)	30041	1,5-di(4-pyridinyl)-3-pentanone		C₁₅H₁₆N₂O	详情	详情
(V)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(VI)	30042	N-benzyl-1,5-di(4-pyridinyl)-3-pentanamine; N-benzyl-N-[3-(4-pyridinyl)-1-[2-(4-pyridinyl)ethyl]propyl]amine		C₂₂H₂₅N₃	详情	详情
(VII)	30043	(2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-(4-chlorophenyl)propionic acid	125324-00-7	C₁₅H₂₀ClNO₄	详情	详情
(VIII)	30044	tert-butyl (1S)-2-(benzyl[3-(4-pyridinyl)-1-[2-(4-pyridinyl)ethyl]propyl]amino)-1-(4-chlorobenzyl)-2-oxoethyl(methyl)carbamate		C₃₇H₄₃ClN₄O₃	详情	详情
(IX)	30045	(2S)-N-benzyl-3-(4-chlorophenyl)-2-(methylamino)-N-[3-(4-pyridinyl)-1-[2-(4-pyridinyl)ethyl]propyl]propanamide		C₃₂H₃₅ClN₄O	详情	详情
(X)	30046	2-oxo-2-(3,4,5-trimethoxyphenyl)acetic acid		C₁₁H₁₂O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XX)

Carboxylic acid (XV) was coupled with cyclopentylamine (XVI) using EDC and HOBt to produce amide (XVII), which was cyclized to the fused pyrazinone derivative (XVIII) by treatment with pyridinium p-toluenesulfonate in toluene. The benzyloxycarbonyl group of (XVIII) was then removed by catalytic hydrogenation to give amine (XIX). This was finally coupled with (3,4,5-trimethoxyphenyl)glyoxylic acid (XX) to yield the title amide.

参考文献中间体

合成目标

【1】 Reich, S.; Guo, C.X.; Villafranca, E.; Showalter, R.; Dong, L.; A concise synthesis of AG5473/5507 utilizing N-acyliminium ion chemistry. Tetrahedron Lett 2000, 41, 28, 5307.
【2】 Tada, H.; Kalish, V.; Kato, S.; Villafranca, J.E.; Tatlock, J.H.; Linton, M.A.; Kawakami, H. (Agouron Pharmaceuticals, Inc.); Cpds., compsns., and methods for stimulating neuronal growth and elongation. WO 0004020 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	43303	2-[9-[(benzyloxy)carbonyl]-2-(dimethoxymethyl)-4-oxo-3,9-diazabicyclo[3.3.1]non-3-yl]acetic acid		C₂₀H₂₆N₂O₇	详情	详情
(XVI)	28850	cyclopentanamine	1003-03-8	C₅H₁₁N	详情	详情
(XVII)	43313	benzyl 3-[2-(cyclopentylamino)-2-oxoethyl]-2-(dimethoxymethyl)-4-oxo-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate		C₂₅H₃₅N₃O₆	详情	详情
(XVIII)	43314	benzyl 4-cyclopentyl-5,8-dioxo-4,7,13-triazatricyclo[7.3.1.0(2,7)]tridec-2-ene-13-carboxylate		C₂₃H₂₇N₃O₄	详情	详情
(XIX)	43315	4-cyclopentyl-4,7,13-triazatricyclo[7.3.1.0(2,7)]tridec-2-ene-5,8-dione		C₁₅H₂₁N₃O₂	详情	详情
(XX)	30046	2-oxo-2-(3,4,5-trimethoxyphenyl)acetic acid		C₁₁H₁₂O₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XX)

Carboxylic acid (XV) was coupled with 3,5-dimethoxyaniline (XVI) using EDC and HOBt to produce amide (XVII), which was cyclized to the fused pyrazinone derivative (XVIII) by treatment with pyridinium p-toluenesulfonate in toluene. The benzyloxycarbonyl group of (XVIII) was then removed by catalytic hydrogenation to give amine (XIX). This was finally coupled with (3,4,5-trimethoxyphenyl)glyoxylic acid (XX) to yield the title amide.

参考文献中间体

合成目标

【1】 Reich, S.; Guo, C.X.; Villafranca, E.; Showalter, R.; Dong, L.; A concise synthesis of AG5473/5507 utilizing N-acyliminium ion chemistry. Tetrahedron Lett 2000, 41, 28, 5307.
【2】 Tada, H.; Kalish, V.; Kato, S.; Villafranca, J.E.; Tatlock, J.H.; Linton, M.A.; Kawakami, H. (Agouron Pharmaceuticals, Inc.); Cpds., compsns., and methods for stimulating neuronal growth and elongation. WO 0004020 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	43303	2-[9-[(benzyloxy)carbonyl]-2-(dimethoxymethyl)-4-oxo-3,9-diazabicyclo[3.3.1]non-3-yl]acetic acid		C₂₀H₂₆N₂O₇	详情	详情
(XVI)	25780	3,5-dimethoxyaniline; 3,5-dimethoxyphenylamine	10272-07-8	C₈H₁₁NO₂	详情	详情
(XVII)	43304	benzyl 3-[2-(3,5-dimethoxyanilino)-2-oxoethyl]-2-(dimethoxymethyl)-4-oxo-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate		C₂₈H₃₅N₃O₈	详情	详情
(XVIII)	43305	benzyl 4-(3,5-dimethoxyphenyl)-5,8-dioxo-4,7,13-triazatricyclo[7.3.1.0(2,7)]tridec-2-ene-13-carboxylate		C₂₆H₂₇N₃O₆	详情	详情
(XIX)	43306	4-(3,5-dimethoxyphenyl)-4,7,13-triazatricyclo[7.3.1.0(2,7)]tridec-2-ene-5,8-dione		C₁₈H₂₁N₃O₄	详情	详情
(XX)	30046	2-oxo-2-(3,4,5-trimethoxyphenyl)acetic acid		C₁₁H₁₂O₆	详情	详情

Extended Information