2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone -Drug Synthesis Database

【结构式】

【分子编号】36573

【品名】2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone

【CA登记号】

【分子式】C₁₁H₁₄OS

【分子量】194.29756

【元素组成】C 68% H 7.26% O 8.23% S 16.5%

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：(III)

The Friedel Crafts condensation of thioanisole (I) with isobutyryl chloride (II) by means of AlCl3 gives the propiophenone (III), which is alpha hydroxylated by means of Aliquant 336 and NaOH yielding the alpha hydroxy ketone (IV). The oxidation of the methylsulfanyl group of (IV) with magnesium monoperoxyphthalate (MMPP) affords the corresponding sulfone (V), which is finally cyclized with 2-(3,4-difluorophenoxy)acetic acid (VI) by means of 1-cyclohexyl-3-[2-(4-morpholinyl)ethyl]carbodiimide metho-p-toluenesulfonate (CMC), DMAP and DBU to furnish the target furanone.

参考文献中间体

合成目标

【1】 Brideau, C.; Li, C.-S.; Chan, C.C.; Black, W.C.; et al.; A new structural variation on the methanesulfonylphenyl class of selective cyclooxygenase-2 inhibitors. Bioorg Med Chem Lett 1999, 9, 22, 3181.
【2】 Belley, M.; Gauthier, J.Y.; Grimm, E.; Leblanc, Y.; Li, C.-S.; Therien, M.; Lau, C.-K.; Prasit, P.; Roy, P. (Merck Frosst Canada Inc.); (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors. EP 0863891; JP 1999500146; US 5981576; WO 9714691 .

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)	19722	2-[(3aR,5S,7S,7aS)-7-hydroxy-7-(2-methoxyphenyl)octahydro-1H-isoindol-5-yl]acetonitrile		C₁₇H₂₂N₂O₂	详情	详情
(II)	14932	isobutyryl chloride; 2-methylpropanoyl chloride	79-30-1	C₄H₇ClO	详情	详情
(III)	36573	2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone		C₁₁H₁₄OS	详情	详情
(IV)	36574	2-hydroxy-2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone		C₁₁H₁₄O₂S	详情	详情
(V)	36575	2-hydroxy-2-methyl-1-[4-(methylsulfonyl)phenyl]-1-propanone		C₁₁H₁₄O₄S	详情	详情
(VI)	18826	2-(3,4-difluorophenoxy)acetic acid		C₈H₆F₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Friedel-Crafts acylation of thioanisole (I) with isobutyryl chloride (II) in the presence of AlCl3 gave ketone (III), which was hydroxylated with NaOH and a phase-transfer agent in CCl4-toluene to provide hydroxyketone (IV). Subsequent oxidation of the sulfide group employing Oxone(tm) gave rise to sulfone (V) (1). Further esterification of (V) with chloroacetyl chloride (VI) and pyridine yielded chloroacetate ester (VII), which was cyclized to the epoxy lactone (VIII) by treatment with DBU in acetonitrile. Finally, epoxide opening with the potassium salt of 5-bromo-2-hydroxypyridine (IX) produced the title (pyridyloxy)furanone.

参考文献中间体

合成目标

【1】 Chan, C.C.; Lau, C.K.; Brideau, C.; et al.; Synthesis and biological evaluation of 3-heteroaryloxy-4-phenyl-2(5H)-furanones as selective COX-2 inhibitors. Bioorg Med Chem Lett 1999, 9, 22, 3187.
【2】 Belley, M.; Gauthier, J.Y.; Grimm, E.; Leblanc, Y.; Li, C.-S.; Therien, M.; Lau, C.-K.; Prasit, P.; Roy, P. (Merck Frosst Canada Inc.); (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors. EP 0863891; JP 1999500146; US 5981576; WO 9714691 .

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)	19272	methyl phenyl sulfide; 1-(methylsulfanyl)benzene	100-68-5	C₇H₈S	详情	详情
(II)	14932	isobutyryl chloride; 2-methylpropanoyl chloride	79-30-1	C₄H₇ClO	详情	详情
(III)	36573	2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone		C₁₁H₁₄OS	详情	详情
(IV)	36574	2-hydroxy-2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone		C₁₁H₁₄O₂S	详情	详情
(V)	36575	2-hydroxy-2-methyl-1-[4-(methylsulfonyl)phenyl]-1-propanone		C₁₁H₁₄O₄S	详情	详情
(VI)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(VII)	36576	1,1-dimethyl-2-[4-(methylsulfonyl)phenyl]-2-oxoethyl 2-chloroacetate		C₁₃H₁₅ClO₅S	详情	详情
(VIII)	36577	4,4-dimethyl-5-[4-(methylsulfonyl)phenyl]-3,6-dioxabicyclo[3.1.0]hexan-2-one		C₁₃H₁₄O₅S	详情	详情
(IX)	36578	potassium 5-bromo-2-pyridinolate		C₅H₃BrKNO	详情	详情

Extended Information