1-[(4-methylphenyl)sulfonyl]-1H-imidazole -Drug Synthesis Database

【结构式】

【分子编号】47846

【品名】1-[(4-methylphenyl)sulfonyl]-1H-imidazole

【CA登记号】2232-08-8

【分子式】C₁₀H₁₀N₂O₂S

【分子量】222.26768

【元素组成】C 54.04% H 4.53% N 12.6% O 14.4% S 14.43%

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)

The condensation of aldehyde (I) with boronate (II) in toluene gives the chiral alcohol (III), which is treated with Tbdms-OTf and TEA to yield the silyl ether (IV). The hydroxylation of the terminal double bond of (IV) by means of 9-BBN in refluxing THF affords the primary alcohol (V), which is oxidized by means of the Swern oxidant to provide the aldehyde (VI). The homologation of (VI) with methyltriphenylphosphonium iodide (VII) and NaHMDS gives the unsaturated compound (VIII), which is deprotected at the ketonide group by means of TFA in dichloromethane to afford the diol (IX). The dehydration of (IX) by means of tosylimidazole (X) and NaH in THF provides the epoxide (XI), which is condensed with the Grignard reagent (XIII) (obtained by reaction of the tributyltin derivative (XII) with MgBr2) to give the secondary alcohol (XIV). The reaction of 2-allyl-6-methoxybenzamide (XV) with I2 in THF/water gives the lactone (XVI), which is treated with Zn and AcOH to yield 2-allyl-6-methoxybenzoic acid (XVII). The esterification of acid (XVII) with alcohol (XIV) by means of DEAD and PPH3 affords the corresponding ester (XVIII), which is submitted to a ring closing metathesis reaction by means of a Ru catalyst to provide the macrolactone (XIX). The cleavage of the Pmb protecting group of (XIX) by means of DDQ gives the primary alcohol (XX), which is oxidized to the aldehyde (XXI) by means of DMP oxidant.

参考文献中间体

合成目标

【1】 Smith, A.B.; Zheng, J.Y.; Total synthesis of (-)-salicylihalamide A and related congeners. Tetrahedron 2002, 58, 33, 6455.

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)	61703	2-[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]acetaldehyde		C₉H₁₆O₃	详情	详情
(II)	61704	diisopropyl (4S,5S)-2-[(E)-2-butenyl]-1,3,2-dioxaborolane-4,5-dicarboxylate		C₁₄H₂₃BO₆	详情	详情
(III)	61705	(2R,3S)-1-[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]-3-methyl-4-penten-2-ol		C₁₃H₂₄O₃	详情	详情
(IV)	61706	tert-butyl(dimethyl)silyl (1R,2S)-1-{[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]methyl}-2-methyl-3-butenyl ether; tert-butyl[((1R,2S)-1-{[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]methyl}-2-methyl-3-butenyl)oxy]dimethylsilane		C₁₉H₃₈O₃Si	详情	详情
(V)	61707	(3S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]-3-methyl-1-pentanol		C₁₉H₄₀O₄Si	详情	详情
(VI)	61708	(3S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]-3-methylpentanal		C₁₉H₃₈O₄Si	详情	详情
(VII)	13484	Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide	2065-66-9	C₁₉H₁₈IP	详情	详情
(VIII)	61709	tert-butyl(dimethyl)silyl (1R,2S)-1-{[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]methyl}-2-methyl-4-pentenyl ether; tert-butyl[((1R,2S)-1-{[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]methyl}-2-methyl-4-pentenyl)oxy]dimethylsilane		C₂₀H₄₀O₃Si	详情	详情
(IX)	61710	(2S,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-7-octene-1,2-diol		C₁₅H₃₂O₃Si	详情	详情
(X)	47846	1-[(4-methylphenyl)sulfonyl]-1H-imidazole	2232-08-8	C₁₀H₁₀N₂O₂S	详情	详情
(XI)	61711	tert-butyl(dimethyl)({(1R,2S)-2-methyl-1-[(2S)oxiranylmethyl]-4-pentenyl}oxy)silane; tert-butyl(dimethyl)silyl (1R,2S)-2-methyl-1-[(2S)oxiranylmethyl]-4-pentenyl ether		C₁₅H₃₀O₂Si	详情	详情
(XII)	61712	tributyl{(E)-3-[(4-methoxybenzyl)oxy]-1-propenyl}stannane; 4-methoxybenzyl (E)-3-(tributylstannyl)-2-propenyl ether		C₂₃H₄₀O₂Sn	详情	详情
(XIII)	61713	bromo{(E)-3-[(4-methoxybenzyl)oxy]-1-propenyl}magnesium		C₁₁H₁₃BrMgO₂	详情	详情
(XIV)	61716	(2E,5R,7R,8S)-7-{[tert-butyl(dimethyl)silyl]oxy}-1-[(4-methoxybenzyl)oxy]-8-methyl-2,10-undecadien-5-ol		C₂₆H₄₄O₄Si	详情	详情
(XV)	61714	2-allyl-6-methoxy-N,N-dipropylbenzamide		C₁₇H₂₅NO₂	详情	详情
(XVI)	61715	3-(iodomethyl)-8-methoxy-3,4-dihydro-1H-isochromen-1-one		C₁₁H₁₁IO₃	详情	详情
(XVII)	47491	2-allyl-6-methoxybenzoic acid		C₁₁H₁₂O₃	详情	详情
(XVIII)	61717	(1S,3R,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-1-{(E)-4-[(4-methoxybenzyl)oxy]-2-butenyl}-4-methyl-6-heptenyl 2-allyl-6-methoxybenzoate		C₃₇H₅₄O₆Si	详情	详情
(XIX)	61718	(3S,5R,6S)-5-{[tert-butyl(dimethyl)silyl]oxy}-14-methoxy-3-{(E)-4-[(4-methoxybenzyl)oxy]-2-butenyl}-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-1-one		C₃₅H₅₀O₆Si	详情	详情
(XX)	61719	(3S,5R,6S)-5-{[tert-butyl(dimethyl)silyl]oxy}-3-[(E)-4-hydroxy-2-butenyl]-14-methoxy-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-1-one		C₂₇H₄₂O₅Si	详情	详情
(XXI)	61720	(E)-4-((3S,5R,6S)-5-{[tert-butyl(dimethyl)silyl]oxy}-14-methoxy-6-methyl-1-oxo-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-3-yl)-2-butenal		C₂₇H₄₀O₅Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVIII)

After protection of (XVI) as the N-Boc derivative (XVII), the diol function was cyclized to epoxide (XIX) by treatment with N-tosyl imidazole (XVIII) in the presence of NaH. Epoxide (XIX) opening with the potassium salt of 4-quinazolinone (XX) gave alcohol (XXI). Subsequent Dess-Martin oxidation of (XXI) yielded the epimeric mixture of ketones (XXII). Acid hydrolysis of this mixture furnished the title trans-piperidine along with the cis-isomer, which was isolated in the cyclic hemiacetal form (XXIII). The title compound was also obtained by isomerization of (XXIII) in refluxing MeOH).

参考文献中间体

合成目标

【1】 Ooi, H.e; et al.; A concise enantioselective synthesis of antimalarial febrifugine alkaloids. Org Lett 2001, 3, 6, 953.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVI)	47844	3-((3S)-3-[[tert-butyl(diphenyl)silyl]oxy]piperidinyl)-1,2-propanediol		C₂₄H₃₅NO₃Si	详情	详情
(XVII)	47845	tert-butyl (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-(2,3-dihydroxypropyl)-1-piperidinecarboxylate		C₁₉H₃₉NO₅Si	详情	详情
(XVIII)	47846	1-[(4-methylphenyl)sulfonyl]-1H-imidazole	2232-08-8	C₁₀H₁₀N₂O₂S	详情	详情
(XIX)	47847	tert-butyl (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-(2-oxiranylmethyl)-1-piperidinecarboxylate		C₁₉H₃₇NO₄Si	详情	详情
(XX)	14634	4(3H)-quinazolinone		C₈H₆N₂O	详情	详情
(XXI)	47848	tert-butyl (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[2-hydroxy-3-[4-oxo-3(4H)-quinazolinyl]propyl]-1-piperidinecarboxylate		C₂₇H₄₃N₃O₅Si	详情	详情
(XXII)	47849	tert-butyl (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[2-oxo-3-[4-oxo-3(4H)-quinazolinyl]propyl]-1-piperidinecarboxylate		C₂₇H₄₁N₃O₅Si	详情	详情
(XXIII)	38272	3-[[(3aS,7aS)-2-hydroxyoctahydrofuro[3,2-b]pyridin-2-yl]methyl]-4(3H)-quinazolinone		C₁₆H₁₉N₃O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XVIII)

After protection of (XVI) as the N-Boc derivative (XVII), the diol function was cyclized to epoxide (XIX) by treatment with N-tosyl imidazole (XVIII) in the presence of NaH. Epoxide (XIX) opening with the potassium salt of 4-quinazolinone (XX) gave alcohol (XXI). Subsequent Dess-Martin oxidation of (XXI) yielded the epimeric mixture of ketones (XXII). Acid hydrolysis of this mixture furnished the trans-piperidine (XXIII) along with the title cis-isomer, which was isolated in the cyclic hemiacetal form.

参考文献中间体

合成目标

【1】 Ooi, H.e; et al.; A concise enantioselective synthesis of antimalarial febrifugine alkaloids. Org Lett 2001, 3, 6, 953.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVI)	47844	3-((3S)-3-[[tert-butyl(diphenyl)silyl]oxy]piperidinyl)-1,2-propanediol		C₂₄H₃₅NO₃Si	详情	详情
(XVII)	47845	tert-butyl (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-(2,3-dihydroxypropyl)-1-piperidinecarboxylate		C₁₉H₃₉NO₅Si	详情	详情
(XVIII)	47846	1-[(4-methylphenyl)sulfonyl]-1H-imidazole	2232-08-8	C₁₀H₁₀N₂O₂S	详情	详情
(XIX)	47847	tert-butyl (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-(2-oxiranylmethyl)-1-piperidinecarboxylate		C₁₉H₃₇NO₄Si	详情	详情
(XX)	14634	4(3H)-quinazolinone		C₈H₆N₂O	详情	详情
(XXI)	47848	tert-butyl (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[2-hydroxy-3-[4-oxo-3(4H)-quinazolinyl]propyl]-1-piperidinecarboxylate		C₂₇H₄₃N₃O₅Si	详情	详情
(XXII)	47849	tert-butyl (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[2-oxo-3-[4-oxo-3(4H)-quinazolinyl]propyl]-1-piperidinecarboxylate		C₂₇H₄₁N₃O₅Si	详情	详情
(XXIII)	47850	3-[3-[(2R,3S)-3-hydroxypiperidinyl]-2-oxopropyl]-4(3H)-quinazolinone		C₁₆H₁₉N₃O₃	详情	详情

Extended Information