4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}-1lambda~4~,4-thiazinan-1-one -Drug Synthesis Database

【结构式】

【分子编号】56308

【品名】4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}-1lambda~4~,4-thiazinan-1-one

【CA登记号】

【分子式】C₁₄H₁₈FN₃O₃S

【分子量】327.3797432

【元素组成】C 51.36% H 5.54% F 5.8% N 12.84% O 14.66% S 9.79%

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：(IV)

The known thiomorpholine derivative (I) was oxidized to the corresponding sulfoxide (II) employing either sodium metaperiodate or osmium tetroxide in the presence of N-methylmorpholine-N-oxide. Sulfonylation of the primary hydroxyl group of (II) with 3-nitrobenzenesulfonyl chloride and Et3N gave rise to the nosylate (IV), which was then displaced with ammonium hydroxide to furnish amine (IV). This was finally condensed with ethyl dithioacetate to produce the target thioacetamide.

参考文献中间体

合成目标

【1】 Hester, J.B. Jr.; Perricone, S.C.; Nidy, E.G.; Poel, T.-J. (Pharmacia Corp.); Oxazolidinone antibacterial agents having a thiocarbonyl functionality. EP 0984947; JP 2002501530; US 6218413; WO 9854161 .
【2】 Hester, J.B. Jr.; Perricone, S.C.; Nidy, E.G.; Poel, T.-J. (Pharmacia Corp.); Oxazolidinone antibacterial agents having a thiocarbonyl functionality. EP 1133493; JP 2002531455; WO 0032599 .
【3】 Mesfin, G.-M.; Jensen, R.K. (Pharmacia Corp.); Use of thioamide oxazolidinones for the treatment of bone resorption and osteoporosis. WO 0180841 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	56305	(5R)-3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one	C₁₄H₁₇FN₂O₃S	详情	详情
(II)	56306	4-{2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}-1lambda~4~,4-thiazinan-1-one	C₁₄H₁₇FN₂O₄S	详情	详情
(III)	56307	{(5R)-3-[3-fluoro-4-(1-oxo-1lambda~4~,4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl 3-nitrobenzenesulfonate	C₂₀H₂₀FN₃O₈S₂	详情	详情
(IV)	56308	4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}-1lambda~4~,4-thiazinan-1-one	C₁₄H₁₈FN₃O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The title compound is prepared by solid phase synthesis utilizing a chloro-derivatized Sasrin resin. Coupling of aminomethyl oxazolidinone (I) to the chloromethyl resin affords the amine bound resin (II). This is then acylated with the cinnamic acid derivative (III) by means of HATU to furnish the corresponding amide (IV). Finally, cleavage of the target amide from resin (IV) is effected by treatment with 10% trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Zhou, J.; et al.; Combinatorial lead optimization of oxazolidinones: In vitro activity of novel 5-amidomethyl thiomorpholine S-oxide and S,S-dioxide phenyloxazolidiones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1319.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	56308	4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}-1lambda~4~,4-thiazinan-1-one	C₁₄H₁₈FN₃O₃S	详情	详情
(II)	56308	4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}-1lambda~4~,4-thiazinan-1-one	C₁₄H₁₈FN₃O₃S	详情	详情
(III)	62247	(E)-3-{4-[(methoxyimino)methyl]phenyl}-2-propenoic acid	C₁₁H₁₁NO₃	详情	详情
(IV)	62248	(E)-N-({(5S)-3-[3-fluoro-4-(1-oxo-1lambda~4~,4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)-3-{4-[(methoxyimino)methyl]phenyl}-2-propenamide	C₂₅H₂₇FN₄O₅S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】 Zhou, J.; et al.; Combinatorial lead optimization of oxazolidinones: In vitro activity of novel 5-amidomethyl thiomorpholine S-oxide and S,S-dioxide phenyloxazolidiones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1319.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	56308	4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}-1lambda~4~,4-thiazinan-1-one	C₁₄H₁₈FN₃O₃S	详情	详情
(II)	56308	4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}-1lambda~4~,4-thiazinan-1-one	C₁₄H₁₈FN₃O₃S	详情	详情
(III)	62247	(E)-3-{4-[(methoxyimino)methyl]phenyl}-2-propenoic acid	C₁₁H₁₁NO₃	详情	详情
(IV)	62248	(E)-N-({(5S)-3-[3-fluoro-4-(1-oxo-1lambda~4~,4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)-3-{4-[(methoxyimino)methyl]phenyl}-2-propenamide	C₂₅H₂₇FN₄O₅S	详情	详情

Extended Information