2,3-Dimethylphenylamine; 2,3-Dimethylaniline; 2,3-Xylidine -Drug Synthesis Database

【结构式】

【分子编号】23025

【品名】2,3-Dimethylphenylamine; 2,3-Dimethylaniline; 2,3-Xylidine

【CA登记号】87-59-2

【分子式】C₈H₁₁N

【分子量】121.18208

【元素组成】C 79.29% H 9.15% N 11.56%

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：(I)

1) The cyclization of 2,3-dimethylaniline (I) with diethyl acetylmalonate (II) in 1-chloronaphthalene at 240 C gives 3-acetyl-4-hydroxy-7,8-dimethylquinolin-2(1H)-one (III), which by reaction with diethyl oxalate (IV) by means of sodium ethoxide in refluxing benzene yields ethyl-4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydroquinolin-3yl)-2,4-dioxo-butanoate (V). The cyclization of (V) in acetic acid concentrated HCl at 100 C affords 5,6-dihydro-7,8 dimethyl-4,5-dioxo-4H-pyrano[3,2-c]quinoline-2-carboxylic acid (VI), which is converted into the corresponding acyl chloride (VII) by reaction with refluxing SOCl2. Finally, this compound is treated with hot 3-methylbutanol (VIII).

参考文献中间体

合成目标

【1】 Takahashi, K.; Hata, S.; Morinaka, Y.; Yamada, S.; Antiallergic agents I. Pyranoquinoline derivatives. Eur J Med Chem - Chim Ther 1981, 16, 3, 251.
【2】 Castaner, J.; Prous, J.; Repirinast. Drugs Fut 1987, 12, 1, 37.

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)	23025	2,3-Dimethylphenylamine; 2,3-Dimethylaniline; 2,3-Xylidine	87-59-2	C₈H₁₁N	详情	详情
(II)	23026	diethyl 2-acetylmalonate	570-08-1	C₉H₁₄O₅	详情	详情
(III)	23027	3-acetyl-4-hydroxy-7,8-dimethyl-2(1H)-quinolinone		C₁₃H₁₃NO₃	详情	详情
(IV)	17571	Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate	95-92-1	C₆H₁₀O₄	详情	详情
(V)	23029	ethyl 4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydro-3-quinolinyl)-2,4-dioxobutanoate		C₁₇H₁₇NO₆	详情	详情
(VI)	24014	Phenyllithium	591-51-5	C₆H₅Li	详情	详情
(VII)	23031	7,8-dimethyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-2-carbonyl chloride		C₁₅H₁₀ClNO₄	详情	详情
(VIII)	23032	3-methyl-1-butanol	123-51-3	C₅H₁₂O	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 reaction of 2,3-dimethylaniline (I) with chloral hydrate (II) and hydroxylamine in hot aq. HCl gives the isonitrosoacetanilide (III), which is cyclized by means of hot Ms-OH or H2SO4 to yield 6,7-dimethylisatin (IV). The hydrolysis of (IV) by means of KOH and H2O2 in water affords 2-amino-3,4-dimethylbenzoic acid (V), which is diazotized with NaNO2 and H2SO4 and treated with KI to provide 2-iodo-3,4-dimethylbenzoic acid (VI). The condensation of (VI) with the sodium salt of 2-(2-hydroxyphenyl)acetic acid (VII) by means of tris[2-(2-methoxyethoxy)ethyl]amine (TDA) and CuCl in DMSO gives the precursor (VIII), which is finally cyclized by means of hot conc. aq. H2SO4 to furnish the target xanthene derivative.

参考文献中间体

合成目标

【1】 Denny, W.A.; Atwell, G.J.; Yang, S.; An improved synthesis of 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Eur J Med Chem 2002, 37, 10, 825.
【2】 Denny, W.A.; Baguley, B.C.; Atwell, G.J.; Rewcastle, G.W. (Cancer Research UK; Pfizer Inc.); Cpds. having antitumour and antibacterial properties. EP 0278176; US 5281620 .
【3】 Rewcastle, G.W.; et al.; Potential antitumor agents. 61. Structure-activity relationships for in vivo colon 38 activity among disubstituted 9-oxo-9H-xanthene-4-acetic acids. J Med Chem 1991, 34, 1, 217.

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)	23025	2,3-Dimethylphenylamine; 2,3-Dimethylaniline; 2,3-Xylidine	87-59-2	C₈H₁₁N	详情	详情
(II)	14018	2,2,2-Trichloro-1,1-ethanediol; Chloral hydrate	302-17-0	C₂H₃Cl₃O₂	详情	详情
(III)	56664	N-(2,3-dimethylphenyl)-2-(hydroxyimino)acetamide		C₁₀H₁₂N₂O₂	详情	详情
(IV)	56665	6,7-dimethyl-1H-indole-2,3-dione		C₁₀H₉NO₂	详情	详情
(V)	56667	2-amino-3,4-dimethylbenzoic acid	50419-58-4	C₉H₁₁NO₂	详情	详情
(VI)	56668	2-iodo-3,4-dimethylbenzoic acid	129833-31-4	C₉H₉IO₂	详情	详情
(VII)	56666	disodium 2-(2-oxidophenyl)acetate		C₈H₆Na₂O₃	详情	详情
(VIII)	56669	2-[2-(carboxymethyl)phenoxy]-3,4-dimethylbenzoic acid	117570-93-1	C₁₇H₁₆O₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

The reaction of 2-thiobarbituric acid (I) with ethyl bromoacetate (II) by means of NaHCO3 in ethanol - water gives ethyl-(4,6-dihydroxy-2-pyrimidinylthio)acetate (III), which by halogenation with POCl3 and N,N-diethylaniline yields ethyl (4,6-dichloro-2-pyrimidinylthio)acetate (IV). The condensation of (IV) with 2,3-dimethylaniline (V) by means of Na2CO3 in refluxing ethanol affords ethyl [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetate (VI), which is finally hydrolyzed with Na2CO3 in refluxing ethanol. Description.- Crystals, m.p. 146-51 C; Na salt, m.p. 183 C (decomp.).

参考文献中间体

合成目标

【1】 Castaner, J.; Paton, D.M.; Wy - 14643. Drugs Fut 1978, 3, 5, 404.
【2】 Santilli, A.A.; et al.; Natural product resveratrol: Novel sensitizer of tumor cells for TRAIL- or cytotoxic drug-induced apoptosis by cell cycle-mediated survivin depletion. Experientia 1974, 30, 10, 1110.
【3】 Santilli, A.A.; et al.; US 3940394 .
【4】 Santilli, A.A.; et al. (American Home Products Corp.); US 3910910 .
【5】 Santilli, A.A.; et al. (American Home Products Corp.); CA 967571; DE 2314160; FR 2182917; GB 1413892; US 3814761; US 3876789; US 3896129; ZA 7301526 .

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)	25623	2-Thiobarbituric acid; 4,5-Dihydroxy-2-mercaptopyrimidine; 2-sulfanyl-4,6-pyrimidinediol	504-17-6	C₄H₄N₂O₂S	详情	详情
(II)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(III)	61116	ethyl 2-[(4,6-dihydroxy-2-pyrimidinyl)sulfanyl]acetate		C₈H₁₀N₂O₄S	详情	详情
(IV)	61117	ethyl 2-[(4,6-dichloro-2-pyrimidinyl)sulfanyl]acetate		C₈H₈Cl₂N₂O₂S	详情	详情
(V)	23025	2,3-Dimethylphenylamine; 2,3-Dimethylaniline; 2,3-Xylidine	87-59-2	C₈H₁₁N	详情	详情
(VI)	61118	ethyl 2-{[4-chloro-6-(2,3-dimethylanilino)-2-pyrimidinyl]sulfanyl}acetate		C₁₆H₁₈ClN₃O₂S	详情	详情

Extended Information