tert-Butyl 2-iodoacetate -Drug Synthesis Database

【结构式】

【分子编号】24735

【品名】tert-Butyl 2-iodoacetate

【CA登记号】

【分子式】C₆H₁₁IO₂

【分子量】242.05661

【元素组成】C 29.77% H 4.58% I 52.43% O 13.22%

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 condensation of 7-aminocephalosporanic acid (I) with 5-methyltetrazole (II) by means of BF3 ethyl ether in sulfolane gives 7-amino-3-(5-methyl-1,2,3,4-tetrazol-2-ylmethyl)-3-cephem-4-carboxylic acid (III), which is esterified with pivaloyloxymethyl iodide (IV) by means of triethylamine in DMF yielding the corresponding ester (V). Finally, this compound it condensed with 2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetic acid (VI) by means of POCl3 and dimethylacetamide in CH2Cl2.

参考文献中间体

合成目标

【1】 Hirakawa, T.; Imaizumi, H.; Inaba, T.; Konishi, Y.; Narita, H.; Sadaki, H.; Saikawa, I.; Tai, M.; Taki, H.; Watanabe, Y. (Toyama Chemical Co., Ltd.); Cephalosporins. AU 8549860; AU 8549863; DE 3137854; US 4489072 .
【2】 Serradell, M.N.; Castaner, J.; Cefteram. Drugs Fut 1986, 11, 9, 732.

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)	15672	7-Aminocephalosporanic acid; 3-[(acetoxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7-ACA		C₁₀H₁₂N₂O₅S	详情	详情
(II)	24726	5-methyl-2H-1,2,3,4-tetraazole	4076-36-2	C₂H₄N₄	详情	详情
(III)	24727	7-amino-3-[(5-methyl-2H-1,2,3,4-tetraazol-2-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid		C₁₀H₁₂N₆O₃S	详情	详情
(IV)	24735	tert-Butyl 2-iodoacetate		C₆H₁₁IO₂	详情	详情
(V)	24736	[(2,2-dimethylpropanoyl)oxy]methyl 7-amino-3-[(5-methyl-2H-1,2,3,4-tetraazol-2-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₁₆H₂₂N₆O₅S	详情	详情
(VI)	24737	2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetic acid	65872-41-5	C₆H₇N₃O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Acylation of 4-piperidone ethylene ketal (I) with 3-chloro-4-fluorobenzoyl chloride (II) in the presence of Et3N gave amide (III). After ketal hydrolysis of (III) using 80% formic acid and CuSO4, treatment of the resulting N-acyl piperidone (IV) with dimethyloxosulfonium methylide provided epoxide (V). Subsequent ring opening of (V) with HF-pyridine complex afforded the fluoro alcohol (VI), which was converted to tosylate (VII). Then, Gabriel synthesis via the corresponding phthalimide (VIII) produced amine (IX). The title compound was then obtained by condensation of 6-(dimethylamino)pyridine-2-carboxaldehyde (X) with amine (IX), followed by reduction of the intermediate imine with KBH4 in MeOH.

参考文献中间体

合成目标

【1】 Koek, W.; Cosi, C.; Jubault, N.; Funes, P.; Assié, M.-B.; Vacher, B.; Kleven, M.; Bonnaud, B.; Novel derivatives of 2-pyridinemethylamine as selective, potent, and orally active agonists at 5-HT1A receptors. J Med Chem 1999, 42, 9, 1648.

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)	11338	1,4-Dioxa-8-azaspiro[4.5]decane; 4-Piperidone ethylene ketal	177-11-7	C₇H₁₃NO₂	详情	详情
(II)	24370	3-chloro-4-fluorobenzoyl chloride	65055-17-6	C₇H₃Cl₂FO	详情	详情
(III)	24371	(3-chloro-4-fluorophenyl)(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)methanone		C₁₄H₁₅ClFNO₃	详情	详情
(IV)	24372	1-(3-chloro-4-fluorobenzoyl)-4-piperidinone		C₁₂H₁₁ClFNO₂	详情	详情
(V)	24373	(3-chloro-4-fluorophenyl)(1-oxa-6-azaspiro[2.5]oct-6-yl)methanone		C₁₃H₁₃ClFNO₂	详情	详情
(VI)	24374	(3-chloro-4-fluorophenyl)[4-fluoro-4-(hydroxymethyl)-1-piperidinyl]methanone		C₁₃H₁₄ClF₂NO₂	详情	详情
(VII)	24735	tert-Butyl 2-iodoacetate		C₆H₁₁IO₂	详情	详情
(VIII)	24336	5-cyano-5H-dibenzo[b,f]azepine		C₁₅H₁₀N₂	详情	详情
(IX)	24337	5-cyano-10-nitro-5H-dibenzo[b,f]azepine		C₁₅H₉N₃O₂	详情	详情
(X)	24381	6-(dimethylamino)-2-pyridinecarbaldehyde		C₈H₁₀N₂O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

Condensation between ethyl 2-oxocyclopentanecarboxylate (I) and thiourea (II) gives rise to the thiouracil derivative (III) (1,2). This is then alkylated with 4-fluorobenzyl chloride (IV) to yield thioether (V). Subsequent alkylation of (V) with tert-butyl iodoacetate (VI) furnishes adduct (VII). Further acidic cleavage of the tert-butyl ester group of (VII) leads to carboxylic acid (VIII) (2,3). Alternatively, intermediate (VIII) is prepared by alkylation of (V) with triflate (IX), followed by alkaline hydrolysis of the resultant methyl ester (X)

参考文献中间体

合成目标

【1】 The identification of clinical candidate SB-480848: A potent inhibitor of lipoprotein-associated phospholipase A2. Bioorg Med Chem Lett 2003, 13, 6, 1067.
【2】 Ife, R.J.; Leach, C.A.; Hickey, D.M.B.; Pinto, I.L.; Smith, S.A.; Stanway, S.J. (GlaxoSmithKline plc); Pyrimidine-4-one derivs. as LDL-PLA 2 inhibitors. EP 1263740; JP 2003523335; US 2002103213; US 6649619; WO 0160805 .
【3】 Mulholland, K.R.; Ross, A.R.; Smith, G.E.; Slater, G.R. (GlaxoSmithKline plc); Novel processes. WO 0316287 .

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)	29947	ethyl 2-oxocyclopentanecarboxylate	611-10-9	C₈H₁₂O₃	详情	详情
(II)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(III)	63490	2-sulfanyl-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one		C₇H₈N₂OS	详情	详情
(IV)	12354	4-Fluorobenzyl chloride; 1-(Chloromethyl)-4-fluorobenzene	352-11-4	C₇H₆ClF	详情	详情
(V)	63491	2-{[(4-fluorophenyl)methyl]sulfanyl}-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one		C₁₄H₁₃FN₂OS	详情	详情
(VI)	24735	tert-Butyl 2-iodoacetate		C₆H₁₁IO₂	详情	详情
(VII)	63492	1,1-dimethylethyl 2-(2-{[(4-fluorophenyl)methyl]sulfanyl}-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetate		C₂₀H₂₃FN₂O₃S	详情	详情
(VIII)	63494	2-(2-{[(4-fluorophenyl)methyl]sulfanyl}-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetic acid		C₁₆H₁₅FN₂O₃S	详情	详情
(IX)	63493	methyl 2-{[(trifluoromethyl)sulfonyl]oxy}acetate		C₄H₅F₃O₅S	详情	详情
(X)	63495	methyl 2-(2-{[(4-fluorophenyl)methyl]sulfanyl}-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetate		C₁₇H₁₇FN₂O₃S	详情	详情

Extended Information