tert-butyl 4-([[(4-methylphenyl)sulfonyl]oxy]methyl)-1-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】49848

【品名】tert-butyl 4-([[(4-methylphenyl)sulfonyl]oxy]methyl)-1-piperidinecarboxylate

【CA登记号】

【分子式】C₁₈H₂₇NO₅S

【分子量】369.48212

【元素组成】C 58.51% H 7.37% N 3.79% O 21.65% S 8.68%

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：(IV)

Ethyl isonipecotate (I) was protected as the N-Boc derivative (II) and then reduced to alcohol (III) using LiAlH4. Treatment of alcohol (III) with p-toluenesulfonyl chloride in the presence of DBU afforded the intermediate tosylate (IV).

参考文献中间体

合成目标

【1】 Hennequin, L.F.A.; Stokes, E.S.E.; Thomas, A.P. (AstraZeneca AB; AstraZeneca plc); Quinazoline derivs. as VEGF inhibitors. WO 0132651 .

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)	17410	Ethyl isonipecotate; ethyl 4-piperidinecarboxylate	1126-09-6	C₈H₁₅NO₂	详情	详情
(II)	49847	1-(tert-butyl) 4-ethyl-1,4-piperidinedicarboxylate; N-Boc-4-Carbethoxypiperidine	142851-03-4	C₁₃H₂₃NO₄	详情	详情
(III)	40399	tert-butyl 4-(hydroxymethyl)-1-piperidinecarboxylate		C₁₁H₂₁NO₃	详情	详情
(IV)	49848	tert-butyl 4-([[(4-methylphenyl)sulfonyl]oxy]methyl)-1-piperidinecarboxylate		C₁₈H₂₇NO₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Nucleophilic substitution of the chloroquinazoline (V) with 4-bromo-2-fluoroaniline (VI) in refluxing isopropanol provided the anilino quinazoline (VII). Subsequent cleavage of the benzyl ether group of (VII) by treatment with hot trifluoroacetic acid gave phenol (VIII), which was condensed with tosylate (IV) to furnish the ether adduct (IX). Acid deprotection of the N-Boc group of (IX) gave piperidine (X). Finally, reductive methylation of (X) using formaldehyde and sodium cyanoborohydride yielded the corresponding N-methyl piperidine.

参考文献中间体

合成目标

【1】 Hennequin, L.F.A.; Stokes, E.S.E.; Thomas, A.P. (AstraZeneca AB; AstraZeneca plc); Quinazoline derivs. as VEGF inhibitors. WO 0132651 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	49848	tert-butyl 4-([[(4-methylphenyl)sulfonyl]oxy]methyl)-1-piperidinecarboxylate		C₁₈H₂₇NO₅S	详情	详情
(V)	31531	benzyl 4-chloro-6-methoxy-7-quinazolinyl ether; 7-(benzyloxy)-4-chloro-6-methoxyquinazoline		C₁₆H₁₃ClN₂O₂	详情	详情
(VI)	14723	4-Bromo-2-fluorophenylamine; 4-Bromo-2-fluoroaniline	367-24-8	C₆H₅BrFN	详情	详情
(VII)	31532	7-(benzyloxy)-N-(4-bromo-2-fluorophenyl)-6-methoxy-4-quinazolinamine; N-[7-(benzyloxy)-6-methoxy-4-quinazolinyl]-N-(4-bromo-2-fluorophenyl)amine		C₂₂H₁₇BrFN₃O₂	详情	详情
(VIII)	31533	4-(4-bromo-2-fluoroanilino)-6-methoxy-7-quinazolinol		C₁₅H₁₁BrFN₃O₂	详情	详情
(IX)	49849	tert-butyl 4-([[4-(4-bromo-2-fluoroanilino)-6-methoxy-7-quinazolinyl]oxy]methyl)-1-piperidinecarboxylate		C₂₆H₃₀BrFN₄O₄	详情	详情
(X)	49850	N-(4-bromo-2-fluorophenyl)-6-methoxy-7-(4-piperidinylmethoxy)-4-quinazolinamine; N-(4-bromo-2-fluorophenyl)-N-[6-methoxy-7-(4-piperidinylmethoxy)-4-quinazolinyl]amine		C₂₁H₂₂BrFN₄O₂	详情	详情

Extended Information