1-Naphthoic acid -Drug Synthesis Database

【结构式】

【分子编号】10106

【品名】1-Naphthoic acid

【CA登记号】86-55-5

【分子式】C₁₁H₈O₂

【分子量】172.18332

【元素组成】C 76.73% H 4.68% O 18.58%

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)

1) The Grignard reaction of 1-bromonaphthalene (I) with Mg in THF and then with [14C]-labeled CO2 gives the corresponding 1-naphthoic acid (II), which by reaction with SO2Cl2 and then with methylamine yields [14C]-N-methyl-1-naphthalenecarboxamide (III). The reduction of (III) with LiAlH4 in refluxing THF affords the corresponding amine (IV). Finally, this compound is condensed with 1-bromo-6,6-dimethylhept-2-en-4-yne (V) by means of Na2CO3 in DMF, and treated with ethanolic HCl.

参考文献中间体

合成目标

【1】 Andres, H.; Carbon-14 labelling of terbinafine, an antimycotic agent. J Label Compd Radiopharm 1989, 27, 11, 1307.

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)	10105	1-Bromonaphthalene	90-11-9	C₁₀H₇Br	详情	详情
(II)	10106	1-Naphthoic acid	86-55-5	C₁₁H₈O₂	详情	详情
(II)	44581	1-naphthoic acid		C₁₁H₈O₂	详情	详情
(III)	10107	N-Methyl-1-naphthamide	3400-33-7	C₁₂H₁₁NO	详情	详情
(III)	44582	N-methyl-1-naphthamide		C₁₂H₁₁NO	详情	详情
(IV)	10108	N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine	65473-13-4	C₁₂H₁₃N	详情	详情
(IV)	44583	N-methyl(1-naphthyl)methanamine; N-methyl-N-(1-naphthylmethyl)amine		C₁₂H₁₃N	详情	详情
(V)	10109	(E)-1-Bromo-6,6-dimethyl-2-hepten-4-yne	78629-21-7	C₉H₁₃Br	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Swern oxidation of N-Boc-S-valinol (I) provided aldehyde (II). After conversion of (II) to the corresponding oxime (III) upon treatment with hydroxylamine, chlorination with N-chlorosuccinimide gave the hydroximinoyl chloride (IV). Reaction of ethyl 2-(bromomethyl)acrylate (V) with phenyllithium (VI) in the presence of CuCN produced ethyl 2-benzylacrylate (VII). The dipolar cycloaddition of the nitrile oxide generated from (IV) to acrylate (VII) furnished the isoxazoline (VIII) as a diastereomeric mixture. The N-Boc protecting group of (VIII) was then cleaved with trifluoroacetic acid to give amine (IX), which was coupled with 2-naphthoic acid (X), yielding amide (XI). The carboxylic acid (XII), resulting from the basic hydrolysis of ethyl ester (XI), was then coupled with the glutamate ester (XIII) to give (XIV).

参考文献中间体

合成目标

【1】 Chung, H.-H.; Park, M.-J.; Min, C.-H.; Kang, C.-Y.; Park, T.-K.; Chang, H.-K.; Lee, T.-H.; Moon, K.-Y.; Kim, E.E.-K.; Oh, Y.-L.; Kim, Y.-M. (LG Chem Ltd.); Caspase inhibitor. WO 0121599; WO 0121600 .

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)	48024	tert-butyl (1S)-1-(hydroxymethyl)-2-methylpropylcarbamate		C₁₀H₂₁NO₃	详情	详情
(II)	47805	tert-butyl (1S)-1-formyl-2-methylpropylcarbamate		C₁₀H₁₉NO₃	详情	详情
(III)	48025	tert-butyl (1S)-1-[(hydroxyimino)methyl]-2-methylpropylcarbamate		C₁₀H₂₀N₂O₃	详情	详情
(IV)	48026	tert-butyl (1S)-1-[chloro(hydroxyimino)methyl]-2-methylpropylcarbamate		C₁₀H₁₉ClN₂O₃	详情	详情
(V)	11328	ethyl 2-(bromomethyl)acrylate	17435-72-2	C₆H₉BrO₂	详情	详情
(VI)	24014	Phenyllithium	591-51-5	C₆H₅Li	详情	详情
(VII)	48027	ethyl 2-benzylacrylate		C₁₂H₁₄O₂	详情	详情
(VIII)	48028	ethyl 5-benzyl-3-[(1S)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-4,5-dihydro-5-isoxazolecarboxylate		C₂₂H₃₂N₂O₅	详情	详情
(IX)	48029	ethyl 3-[(1S)-1-amino-2-methylpropyl]-5-benzyl-4,5-dihydro-5-isoxazolecarboxylate		C₁₇H₂₄N₂O₃	详情	详情
(X)	10106	1-Naphthoic acid	86-55-5	C₁₁H₈O₂	详情	详情
(XI)	48030	ethyl 5-benzyl-3-[(1S)-2-methyl-1-(1-naphthoylamino)propyl]-4,5-dihydro-5-isoxazolecarboxylate		C₂₈H₃₀N₂O₄	详情	详情
(XII)	48031	5-benzyl-3-[(1S)-2-methyl-1-(1-naphthoylamino)propyl]-4,5-dihydro-5-isoxazolecarboxylic acid		C₂₆H₂₆N₂O₄	详情	详情
(XIII)	48032	4-(tert-butyl) 1-methyl (2S)-2-aminobutanedioate		C₉H₁₇NO₄	详情	详情
(XIV)	48033	4-(tert-butyl) 1-methyl (2S)-2-[([5-benzyl-3-[(1S)-2-methyl-1-(1-naphthoylamino)propyl]-4,5-dihydro-5-isoxazolyl]carbonyl)amino]butanedioate		C₃₅H₄₁N₃O₇	详情	详情

Extended Information