bromomethyl acetate -Drug Synthesis Database

【结构式】

【分子编号】12680

【品名】bromomethyl acetate

【CA登记号】590-97-6

【分子式】C₃H₅BrO₂

【分子量】152.9755

【元素组成】C 23.55% H 3.29% Br 52.23% O 20.92%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(VI)

1) The reaction of 3-pyridylcarbonyl chloride (I) with (3S,4R)-2-[3-[1(R)-hyroxyethyl]-2-oxo-4-sulfanylazetidin-1-yl]-2-(triphenylphosphoranylidene)acetic acid allyl ester silver salt (II) in dichloromethane containing pyridine gives the substituted phosphorane (III), which is cyclized in refluxing benzene to afford (5R,6S)-6-[1(R)-hydroxyethyl]-2-(3-pyridyl)-2-penem-3-carboxylic acid allyl ester (IV). The deprotection of (IV) by means of triphenylphosphine, tetrakis(triphenylphosphine)palladium and acetic acid yields the free acid (V), which is finally esterified with bromomethyl acetate (VI) in DMF.

参考文献中间体

合成目标

【1】 Mealy, M.; Castaner, J.; TMA-230. Drugs Fut 1996, 21, 5, 493.
【2】 Bedeschi, A.; Visentin, G.; Perrone, E.; et al.; Synthesis and structure-activity relations in the class 2-(pyridyl)penems. J Antibiot 1990, 43, 3, 306-13.

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)	10753	Nicotinoyl chloride		C₆H₄ClNO	详情	详情
(II)	12676	(3S,4R)-2-[3-(1(R)-Hydroxyethyl)-2-oxo-4-sulfanylazetidin-1-yl]-2-(triphenylphosphanylidene)acetic acid allyl ester S-silver salt		C₂₈H₂₇AgNO₄PS	详情	详情
(III)	12677	allyl 2-[(3S,4R)-3-[(1R)-1-hydroxyethyl]-2-oxo-4-[(3-pyridinylcarbonyl)sulfanyl]azetidinyl]-2-(triphenylphosphoranylidene)acetate		C₃₄H₃₁N₂O₅PS	详情	详情
(IV)	12678	allyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-(3-pyridinyl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₁₆H₁₆N₂O₄S	详情	详情
(V)	12679	(5R,6S)-6-[(1R)-1-Hydroxyethyl]-7-oxo-3-(3-pyridinyl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid		C₁₃H₁₂N₂O₄S	详情	详情
(VI)	12680	bromomethyl acetate	590-97-6	C₃H₅BrO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

2) The reaction of 3-pyridylcarbonyl chloride (I) with (3S,4R)-2-[3-[1(R)-(allyloxycarbonyloxy)ethyl]-2-oxo-4-sulfanylazetidin-1-yl]-2-(triphenylphosphoranylidene)acetic acid allyl ester silver salt (VII) in dichloromethane containing pyridine gives the substituted phosphorane (VIII), which is cyclized in refluxing toluene to afford (5R,6S)-6-[1(R)-(allyloxycarbonyloxy)ethyl]-2-(3-pyridyl)-2-penem-3-carboxylic acid allyl ester (IX). The deprotection of (IX) with tetrakis(triphenylphosphine)palladium, tributyltin hydride and NaHCO3 in THF gives the free acid (X) as the sodium salt, which is finally esterified with bromomethyl acetate.

参考文献中间体

合成目标

【1】 Mealy, M.; Castaner, J.; TMA-230. Drugs Fut 1996, 21, 5, 493.
【2】 Lang, M. (Novartis AG); 2-Pyridyl-penem cpds. EP 0246187; JP 1987263183; US 4826832 .

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)	10753	Nicotinoyl chloride		C₆H₄ClNO	详情	详情
(VI)	12680	bromomethyl acetate	590-97-6	C₃H₅BrO₂	详情	详情
(VII)	12681	(3S,4R)-2-[3-[1(R)-(Allyloxycarbonyloxy)ethyl]-2-oxo-4-sulfanylazetidin-1-yl]-2-(triphenylphosphanylidene)acetic acid allyl ester S-silver salt		C₃₂H₃₁AgNO₆PS	详情	详情
(VIII)	12682	allyl 2-[(3S,4R)-3-((1R)-1-[[(allyloxy)carbonyl]oxy]ethyl)-2-oxo-4-[(3-pyridinylcarbonyl)sulfanyl]azetidinyl]-2-(triphenylphosphoranylidene)acetate		C₃₈H₃₅N₂O₇PS	详情	详情
(IX)	12683	allyl (5R,6S)-6-((1R)-1-[[(allyloxy)carbonyl]oxy]ethyl)-7-oxo-3-(3-pyridinyl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₀H₂₀N₂O₆S	详情	详情
(X)	12684	sodium (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-(3-pyridinyl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₁₃H₁₁N₂NaO₄S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Exposure of pyrrolidine (I) to NO in acetonitrile/ether in the presence of NaOMe in MeOH provides sodium 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (II), which is converted into the desired product by reaction with bromomethyl acetate (III) in DMSO in the presence of Na2CO3 and silver acetate (HgOAc).

参考文献中间体

合成目标

【1】 Saavedra, J.E.; et al.; Targeting nitric oxide (NO) delivery in vivo. Design of a liver-selective NO donor prodrug that blocks tumor necrosis factor-alpha-induced apoptosis and toxicity in the liver. J Med Chem 1997, 40, 13, 1947.
【2】 Booth, M.N.; Keefer, L.K.; Shami, P.J.; Wang, L.Y.; Saavedra, J.E.; Davies, K.M.; Citro, M.L.; Esterase-sensitive nitric oxide donors of the diazeniumdiolate family: In vitro antileukemic activity. J Med Chem 2000, 43, 2, 261.

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)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(II)	47147			C₄H₈N₃NaO₂	详情	详情
(III)	12680	bromomethyl acetate	590-97-6	C₃H₅BrO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

The alkylation of the triazole derivative (I) (compound 293408) with bromomethyl acetate (II) in hot acetonitrile produced the triazolium bromide salt (III). This was then treated either with ion-exchange resin or with a saturated solution of NaCl to produce the desired chloride salt. The analogous alkylation of (I) with iodomethyl acetate (IV) produced the iodide salt (V), which was finally converted to the corresponding chloride by treatment with a saturated solution of NaCl.

参考文献中间体

合成目标

【1】 Itoh, K.; Okonogi, K.; Kitazaki, T. (Takeda Chemical Industries, Ltd.); Azole cpds., their production and their use. EP 0973768; JP 1999228548; JP 2000198773; WO 9843970 .

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)	45518	1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1,2,3,4-tetraazol-1-yl)phenyl]-2-imidazolidinone		C₂₂H₂₁F₂N₉O₂	详情	详情
(II)	12680	bromomethyl acetate	590-97-6	C₃H₅BrO₂	详情	详情
(III)	45519	4-[(acetoxy)methyl]-1-((2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1,2,3,4-tetraazol-1-yl)phenyl]-1-imidazolidinyl]butyl)-1H-1,2,4-triazol-4-ium bromide		C₂₅H₂₆BrF₂N₉O₄	详情	详情
(IV)	45520	iodomethyl acetate		C₃H₅IO₂	详情	详情
(V)	45521	4-[(acetoxy)methyl]-1-((2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1,2,3,4-tetraazol-1-yl)phenyl]-1-imidazolidinyl]butyl)-1H-1,2,4-triazol-4-ium iodide		C₂₅H₂₆F₂IN₉O₄	详情	详情

Extended Information