(1R,4S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】41620

【品名】(1R,4S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride

【CA登记号】

【分子式】C₁₀H₁₃ClO₃

【分子量】216.66412

【元素组成】C 55.44% H 6.05% Cl 16.36% O 22.15%

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：(VI)

4-Methyl-7-hydroxycoumarin (I) was alkylated with 3-chloro-3-methyl-1-butyne (II) in the presence of K2CO3 and KI to afford the corresponding aryl propargyl ether (III). Claisen rearrangement of (III) in refluxing diethylaniline furnished the tricyclic system (IV). The target 3'R,4'R-dihydroxylated derivative (V) was obtained by Sharpless asymmetric dihydroxylation of (IV) with hydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQ)2-PYR) as the chiral catalyst. Diol (V) was finally esterified with (-)-S-camphanoyl chloride (VI) to afford the title diester.

参考文献中间体

合成目标

【1】 Xie, L.; Takeuchi, Y.; Cosentino, L.M.; Lee, K.-H.; Anti-AIDS agent 33. Synthesis and anti-HIV activity of mono-methyl substituted 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogues. Bioorg Med Chem Lett 1998, 8, 16, 2151.
【2】 Takeuchi, Y.; Xie, L.; Lee, K.-H.; Cosentino, L.M.; Anti-AIDS agents. 37.(1) synthesis and structure-activity relationships of (3'R,4'R)-(+)-cis-khellactone derivatives as novel potent anti-HIV agents. J Med Chem 1999, 42, 14, 2662.

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)	47997	7-hydroxy-4-methyl-2H-chromen-2-one	90-33-5	C₁₀H₈O₃	详情	详情
(II)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(III)	47998	7-[(1,1-dimethyl-2-propynyl)oxy]-4-methyl-2H-chromen-2-one		C₁₅H₁₄O₃	详情	详情
(IV)	47999	4,8,8-trimethyl-2H,8H-pyrano[2,3-f]chromen-2-one		C₁₅H₁₄O₃	详情	详情
(V)	48000	(9R,10R)-9,10-dihydroxy-4,8,8-trimethyl-9,10-dihydro-2H,8H-pyrano[2,3-f]chromen-2-one		C₁₅H₁₆O₅	详情	详情
(VI)	41620	(1R,4S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride		C₁₀H₁₃ClO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

7-Aminoquinolin-2-one (III) was prepared by Knorr cyclization of m-phenylenediamine (I) with ethyl acetoacetate (II). Subsequent diazotization of (II), followed by acid hydrolysis gave rise to the 7-hydroxyquinolinone (IV). Alkylation of (IV) with 3-chloro-3-methylbut-1-yne (V), followed by Claisen rearrangement of the resulting propargyl ether (V) afforded the pyranoquinolinone (VII). This was protected as the N-Boc derivative (VIII) by treatment with Boc2O and Et3N. Sharpless asymmetric dihydroxylation of (VIII) using dihydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQ)2-PYR) as the chiral catalyst furnished the (R,R)-diol (IX), which was esterified with (-)-(S)-camphanoyl chloride (X) to produce diester (XI). The Boc protecting group of (XI) was finally removed by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Cosentino, L.M.; Xia, Y.; Yang, Z.-Y.; Brossi, A.; Lee, K.-H.; Anti-AIDS agents Part 41: Synthesis and anti-HIV activity of 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) lactam analogues. Bioorg Med Chem Lett 2000, 10, 10, 1003.

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)	41612	1,3-benzenediamine; 3-aminophenylamine	108-45-2	C₆H₈N₂	详情	详情
(II)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情
(III)	41613	7-amino-4-methyl-2(1H)-quinolinone	19840-99-4	C₁₀H₁₀N₂O	详情	详情
(IV)	41614	7-hydroxy-4-methyl-2(1H)-quinolinone		C₁₀H₉NO₂	详情	详情
(V)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(VI)	41615	7-[(1,1-dimethyl-2-propynyl)oxy]-4-methyl-2(1H)-quinolinone		C₁₅H₁₅NO₂	详情	详情
(VII)	41616	4,8,8-trimethyl-1,8-dihydro-2H-pyrano[2,3-h]quinolin-2-one		C₁₅H₁₅NO₂	详情	详情
(VIII)	41617	tert-butyl 4,8,8-trimethyl-2-oxo-2H-pyrano[2,3-h]quinoline-1(8H)-carboxylate		C₂₀H₂₃NO₄	详情	详情
(IX)	41618	tert-butyl (9R,10R)-9,10-dihydroxy-4,8,8-trimethyl-2-oxo-9,10-dihydro-2H-pyrano[2,3-h]quinoline-1(8H)-carboxylate		C₂₀H₂₅NO₆	详情	详情
(X)	41620	(1R,4S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride		C₁₀H₁₃ClO₃	详情	详情
(XI)	41619	tert-butyl (9R,10R)-4,8,8-trimethyl-2-oxo-9,10-bis([[(4S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]hept-1-yl]carbonyl]oxy)-9,10-dihydro-2H-pyrano[2,3-h]quinoline-1(8H)-carboxylate		C₄₀H₄₉NO₁₂	详情	详情

Extended Information