glyoxal; 2-oxoacetaldehyde -Drug Synthesis Database

【结构式】

【分子编号】32557

【品名】glyoxal; 2-oxoacetaldehyde

【CA登记号】107-22-2

【分子式】C₂H₂O₂

【分子量】58.03668

【元素组成】C 41.39% H 3.47% O 55.14%

与该中间体有关的原料药合成路线共 5 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5

合成路线1

该中间体在本合成路线中的序号：(II)

6-Quinoxalinecarboxylic acid (III) was prepared by condensation of 3,4-diaminobenzoic acid (I) with glyoxal (II). The title amide was then prepared by coupling of acid (III) with piperidine (VI) via formation of the mixed anhydride (IV) with pivaloyl chloride and Et3N or, alternatively, via activation of (III) as the imidazolide (V) by treatment with carbonyldiimidazole

参考文献中间体

合成目标

【1】 Lynch, G.S.; Rogers, G.A. (University of California, Oakland); Drugs that enhance synaptic responses mediated by AMPA receptors. EP 1156043; JP 1995509468; WO 9402475 .

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)	62528			C₇H₈N₂O₂	详情	详情
(II)	32557	glyoxal; 2-oxoacetaldehyde	107-22-2	C₂H₂O₂	详情	详情
(III)	62529	6-quinoxalinecarboxylic acid		C₉H₆N₂O₂	详情	详情
(IV)	62530	1,1-dimethylpropanoic 6-quinoxalinecarboxylic anhydride		C₁₄H₁₄N₂O₃	详情	详情
(V)	62531	1H-imidazol-1-yl(6-quinoxalinyl)methanone		C₁₂H₈N₄O	详情	详情
(VI)	10158	Piperidine	110-89-4	C₅H₁₁N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Condensation of primary amine (I) with 1,1-bis(methylthio)-2-nitroethene (II) in refluxing acetonitrile afforded adduct (III). Displacement of the methylthio group of (III) by hydrazine yielded compound (IV), which was finally condensed with glyoxal (V) in the presence of Triton B to produce the target pyridazine.

参考文献中间体

合成目标

【1】 Chapman, J.M. Jr.; Sowell, W.; Tang, Y.; Kosh, J.W.; Valli, M.J.; Synthesis and cholinergic properties of N-aryl-2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethylamino analogs of ranitidine. J Med Chem 1992, 35, 17, 3141.

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)	13851	2-[([5-[(Dimethylamino)methyl]-2-furyl]methyl)sulfanyl]-1-ethanamine; N-[(5-[[(2-Aminoethyl)sulfanyl]methyl]-2-furyl)methyl]-N,N-dimethylamine		C₁₀H₁₈N₂OS	详情	详情
(II)	13853	Methyl 1-(methylsulfanyl)-2-nitrovinyl sulfide; 1,1-Bis(methylthio)-2-nitroethylene; 1,1-Bis(methylsulfanyl)-2-nitroethylene	13623-94-4	C₄H₇NO₂S₂	详情	详情
(III)	32555	(E)-N-[2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-1-(methylsulfanyl)-2-nitro-1-ethenamine; N-[2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine		C₁₃H₂₁N₃O₃S₂	详情	详情
(IV)	32556	N-[2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-N-[(E)-1-hydrazino-2-nitroethenyl]amine; (E)-N-[2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-1-hydrazino-2-nitro-1-ethenamine		C₁₂H₂₁N₅O₃S	详情	详情
(V)	32557	glyoxal; 2-oxoacetaldehyde	107-22-2	C₂H₂O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Treatment of (R,R)-1,2-diaminocyclohexane (I) with triphenylmethyl chloride produced the N-trityl derivative (II). Subsequent condensation of (II) with glyoxal (III) gave the bis-imine (IV), which was reduced to amine (V) using LiBH4. Cleavage of the N-trityl groups of (V) with HCl in acetone afforded tetraamine (VI). This was then condensed with 2,6-diacetylpyridine (VII) in the presence of MnCl2 to furnish the cyclic bis-imine manganese complex (VIII). Finally, transfer hydrogenation of the imine functions of (VIII) using ammonium formate and Pd/C produced the cyclic pentaamino derivative as a diastereomeric mixture. The title isomer was then purified by separative partition between H2O and CH2Cl2.

参考文献中间体

合成目标

【1】 Udipi, K.; Joardar, S.; Forster, D.; Riley, D.; Henke, S.; Brethaur, K.; Thurmond, B.; Ornberg, R. (Pharmacia Corp.); Biomaterials modified with superoxide dismutase mimics. WO 0072893 .

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)	11130	(1R,2R)-1,2-cyclohexanediamine; (1R,2R)-2-aminocyclohexylamine; cis-1,2-Diaminocyclohexane	20439-47-8	C₆H₁₄N₂	详情	详情
(II)	48511	N-[(1R,2R)-2-aminocyclohexyl]-N-tritylamine; (1R,2R)-N(1)-trityl-1,2-cyclohexanediamine		C₂₅H₂₈N₂	详情	详情
(III)	32557	glyoxal; 2-oxoacetaldehyde	107-22-2	C₂H₂O₂	详情	详情
(IV)	48512	(1R,2R)-N(1)-trityl-N(2)-((E)-2-[[(1R,2R)-2-(tritylamino)cyclohexyl]imino]ethylidene)-1,2-cyclohexanediamine; N-trityl-N-[(1R,2R)-2-[((E)-2-[[(1R,2R)-2-(tritylamino)cyclohexyl]imino]ethylidene)amino]cyclohexyl]amine		C₅₂H₅₄N₄	详情	详情
(V)	48513	(1R,2R)-N(1)-trityl-N(2)-(2-[[(1R,2R)-2-(tritylamino)cyclohexyl]amino]ethyl)-1,2-cyclohexanediamine; N-trityl-N-[(1R,2R)-2-[(2-[[(1R,2R)-2-(tritylamino)cyclohexyl]amino]ethyl)amino]cyclohexyl]amine		C₅₂H₅₈N₄	详情	详情
(VI)	48514	(1R,2R)-N(1)-(2-[[(1R,2R)-2-aminocyclohexyl]amino]ethyl)-1,2-cyclohexanediamine; N-[(1R,2R)-2-aminocyclohexyl]-N-(2-[[(1R,2R)-2-aminocyclohexyl]amino]ethyl)amine		C₁₄H₃₀N₄	详情	详情
(VII)	48515	2,6-Diacetylpyridine	1129-30-2	C₉H₉NO₂	详情	详情
(VIII)	48516	(4R,9R,14R,19R)-2,21-dimethyl-3,10,13,20,26-pentaazatetracyclo[20.3.1.0(4,9).0(14,19)]hexacosa-1(26),2,20,22,24-pentaene		C₂₃H₃₅N₅	详情	详情

合成路线4

该中间体在本合成路线中的序号：(VIII)

The cyclization of 1-(2-fluorobenzyl)pyrazolo[3,4-b]pyridine-3-carboxamidine (I) (see scheme no. 28591301a, intermediate (IX)) with phenylazomalononitrile (II) by means of NaOMe in hot DMF gives the pyrimidine (III), which is reduced with H2 over RaNi in hot DMF to yield the triaminopyrimidine (IV). The reductocondensation of (IV) with 2-(tert-butyldimethylsilyloxy)acetaldehyde (V) by means of NaBH3CN in methanol/AcOH affords the adduct (VI), which is desilylated by means of TBAF in THF to provide the 2-hydroxyethylamino derivative (VII). Finally, this compound is cyclized with aqueous glyoxal (VIII) to furnish the target tricyclic compound.

参考文献中间体

合成目标

【1】 Straub, A.; Benet-Buckholz, J.; Fröde, R.; Kern, A.; Kohlsdorfer, C.; Schmitt, P.; Schwarz, T.; Siefert, H.-M.; Stasch, J.-P.; Metabolites of orally active NO-independent pyrazolopyridine stimulators of soluble guanylate cyclase. Bioorg Med Chem 2002, 10, 6, 1711.
【2】 Kern, A.; Stasch, J.-P.; Straub, A.; Dembowsky, K.; Alonso-Alija, C. (Bayer AG); Substd. pyrazole deriv.. DE 10021069; WO 0183490 .

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)	50477	1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide	256376-68-8	C₁₄H₁₂FN₅	详情	详情
(II)	63162	2-[(E)-2-phenyldiazenyl]malononitrile	6017-21-6	C₉H₆N₄	详情	详情
(III)	63163	2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-2-phenyldiazenyl]-4,6-pyrimidinediamine; 6-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-2-phenyldiazenyl]-4-pyrimidinylamine	428854-23-3	C₂₃H₁₈FN₉	详情	详情
(IV)	63164	4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylamine; 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine	428854-24-4	C₁₇H₁₅FN₈	详情	详情
(V)	61170	2-{[tert-butyl(dimethyl)silyl]oxy}acetaldehyde；tert-butyldimethylsilyloxy acetaldehyde	102191-92-4	C₈H₁₈O₂Si	详情	详情
(VI)	63165	N~5~-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine; 6-amino-5-[(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-pyrimidinylamine		C₂₅H₃₃FN₈OSi	详情	详情
(VII)	63166	2-({4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl}amino)-1-ethanol		C₁₉H₁₉FN₈O	详情	详情
(VIII)	32557	glyoxal; 2-oxoacetaldehyde	107-22-2	C₂H₂O₂	详情	详情

合成路线5

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】 Ye FQ, Ding YM, Chen L.et aL. 2005. Synthesis and antibacterial activity of ciprofloxacin derivatives. 药学学报，40 (2): 132～135

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)	11974	Acetaldehyde	75-07-0	C₂H₄O	详情	详情
(II)	32557	glyoxal; 2-oxoacetaldehyde	107-22-2	C₂H₂O₂	详情	详情

Extended Information