divinyl sulfone; dioxo(divinyl)-lambda(6)-sulfane -Drug Synthesis Database

【结构式】

【分子编号】35813

【品名】divinyl sulfone; dioxo(divinyl)-lambda(6)-sulfane

【CA登记号】77-77-0

【分子式】C₄H₆O₂S

【分子量】118.15644

【元素组成】C 40.66% H 5.12% O 27.08% S 27.14%

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)

2,5-Bis(p-bromophenyl)furan (II) was prepared by cyclodehydration of diketone (I) in refluxing acetic anhydride. Displacement of both bromine atoms by copper(I) cyanide in boiling quinoline generated the dicyano derivative (V). Alternatively, furan (V) was prepared by addition of p-cyanobenzaldehyde (III) to divinyl sulfone (IV) in the presence of a thiazolium catalyst. After conversion of the cyano groups of (V) into bis-imidate (VI), reaccion with ethanolic ammonia furnished amidine (VII). The stable symmetrical carbonate (X) was obtained by reaction of p-fluorophenyl chloroformate (VIII) with p-fluorophenol (IX) in the presence of pyridine. Finally, reaction of the bis(amidine) compound (VII) with carbonate (X) yielded the title compound.

参考文献中间体

合成目标

【1】 Kawada, A.; Aragane, Y.; Maeda, A.; Tezuka, T.; Heterocycl Commun 1996, 2, 2, 135-140.
【2】 Das, B.P.; Boykin, D.W.; Synthesis and antiprotozoal activity of 2,5-bis (4-guanylphenyl) furans. J Med Chem 1977, 20, 4, 531-536.
【3】 Rahmathullah, S.M.; et al.; Prodrugs for amidines: Synthesis and anti-Pneumocystis carinii activity of carbamates of 2,5-bis(4-amidinophenyl)furan. J Med Chem 1999, 42, 19, 3994.

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)	35811	1,4-bis(4-bromophenyl)-1,4-butanedione		C₁₆H₁₂Br₂O₂	详情	详情
(II)	35812	2,5-bis(4-bromophenyl)furan		C₁₆H₁₀Br₂O	详情	详情
(III)	17552	4-formylbenzonitrile; 4-Cyanobenzaldehyde	105-07-7	C₈H₅NO	详情	详情
(IV)	35813	divinyl sulfone; dioxo(divinyl)-lambda(6)-sulfane	77-77-0	C₄H₆O₂S	详情	详情
(V)	35814	4-[5-(4-cyanophenyl)-2-furyl]benzonitrile		C₁₈H₁₀N₂O	详情	详情
(VI)	35815	ethyl 4-(5-[4-[ethoxy(imino)methyl]phenyl]-2-furyl)benzenecarboximidoate		C₂₂H₂₂N₂O₃	详情	详情
(VII)	35816	4-(5-[4-[amino(imino)methyl]phenyl]-2-furyl)benzenecarboximidamide		C₁₈H₁₆N₄O	详情	详情
(VIII)	35817	1-[(chlorocarbonyl)oxy]-4-fluorobenzene	38377-38-7	C₇H₄ClFO₂	详情	详情
(IX)	19639	4-fluorophenol	371-41-5	C₆H₅FO	详情	详情
(X)	35818	bis(4-fluorophenyl) carbonate		C₁₃H₈F₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

In an improved procedure, conjugate addition of divinyl sulfone (II) to 2,6-difluoroaniline (I) in the presence of AlCl3 leads to the N-aryl thiomorpholine sulfone (III). Aromatic nitration of (III) with fuming HNO3 in AcOH affords (IV). The nitroaryl derivative (IV) is then reduced to aniline (V) by catalytic hydrogenation over Raney Ni. Condensation of aniline (V) with isobutyl chloroformate furnishes carbamate (VI). This is finally cyclized with (S)-N-(2-acetoxy-3-chloropropyl)acetamide (VII) to generate the target oxazolidinone compound.

参考文献中间体

合成目标

【1】 Greene, M.L.; et al.; Synthetic studies leading to the identification of PNU-288034, a potent new oxazolidinone antibacterial agent. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1333.
【2】 Zurenko, G.E.; Barbachyn, M.R. (Pharmacia Corp.); A thiazine oxazolidinone. EP 1294717; US 2002156072; US 6605609; WO 0198297 .

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)	17933	2,6-Difluorophenylamine; 2,6-Difluoroaniline	5509-65-9	C₆H₅F₂N	详情	详情
(II)	35813	divinyl sulfone; dioxo(divinyl)-lambda(6)-sulfane	77-77-0	C₄H₆O₂S	详情	详情
(III)	62754	4-(2,6-difluorophenyl)-1lambda~6~,4-thiazinane-1,1-dione		C₁₀H₁₁F₂NO₂S	详情	详情
(IV)	62755	4-(2,6-difluoro-4-nitrophenyl)-1lambda~6~,4-thiazinane-1,1-dione		C₁₀H₁₀F₂N₂O₄S	详情	详情
(V)	62756	4-(4-amino-2,6-difluorophenyl)-1lambda~6~,4-thiazinane-1,1-dione		C₁₀H₁₂F₂N₂O₂S	详情	详情
(VI)	62757	isobutyl 4-(1,1-dioxo-1lambda~6~,4-thiazinan-4-yl)-3,5-difluorophenylcarbamate		C₁₅H₂₀F₂N₂O₄S	详情	详情
(VII)	61915	(1S)-2-(acetylamino)-1-(chloromethyl)ethyl acetate		C₇H₁₂ClNO₃	详情	详情

Extended Information