4-Fluoro-2-methyl-1-nitrobenzene; 2-Nitro-5-fluorotoluene -Drug Synthesis Database

【结构式】

【分子编号】20612

【品名】4-Fluoro-2-methyl-1-nitrobenzene; 2-Nitro-5-fluorotoluene

【CA登记号】446-33-3

【分子式】C₇H₆FNO₂

【分子量】155.1285832

【元素组成】C 54.2% H 3.9% F 12.25% N 9.03% O 20.63%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

The oxidation of 2-nitro-5-fluorotoluene (I) with KMnO4 in water gives 2-nitro-5-fluorobenzoic acid (II), which by reduction with H2 over Pd/C in methanol - aqueous HCl yields 2-amino-5-fluorobenzoic acid (III). The reaction of (III) with phosgene in THF aqueous HCl affords 5-fluoroisatoic acid anhydride (IV), which by cyclization with N-methylglycine (V) in OMS at 100 C affords 7-fluoro-4-methyl-3,4-dihydro-2H-1,4-benzodiazepin-2,5(1H)-dione (VI). Finally, this compound is cyclized again with ethyl isocyanacetate (VII) by means of potassium tert-butylate and diethyl chlorophosphate in DMF.

参考文献中间体

合成目标

【1】 Haefely, W.; Hunkeler, W.; Kyburz, E.; Mohler, H.; Pieri, L.; Polc, P.; Gerecke, M. (F. Hoffmann-La Roche AG); Imidazodiazepine derivatives. EP 0027214; GB 2060632; JP 1156968; US 4316839; US 4346033 .
【2】 Blancafort, P.; Castaner, J.; Hillier, K.; Serradell, M.N.; RO-15-1788. Drugs Fut 1982, 7, 6, 402.

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)	20612	4-Fluoro-2-methyl-1-nitrobenzene; 2-Nitro-5-fluorotoluene	446-33-3	C₇H₆FNO₂	详情	详情
(II)	31962	2-Nitro-5-fluorobenzoic acid; 5-Fluoro-2-nitrobenzoic acid	320-98-9	C₇H₄FNO₄	详情	详情
(III)	31963	2-Amino-5-fluorobenzoic acid	446-08-2	C₇H₆FNO₂	详情	详情
(IV)	31964	6-Fluoro-2H-3,1-benzoxazine-2,4(1H)-dione; 5-Fluoroisatoic acid anhydride		C₈H₄FNO₃	详情	详情
(V)	10429	N-Methylglycine; Sarcosine; 2-(Methylamino)acetic acid	107-97-1	C₃H₇NO₂	详情	详情
(VI)	31965	7-Fluoro-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione; 7-Fluoro-4-methyl-3,4-dihydro-2H-1,4-benzodiazepin-2,5(1H)-dione		C₁₀H₉FN₂O₂	详情	详情
(VII)	11877	Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate	105-56-6	C₅H₇NO₂	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 condensation of 4-fluoro-2-methylnitrobenzene (I) with 2,4-dimethyl-1H-imidazole (II) by means of Na2CO3 in hot DMF gives 4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylnitrobenzene (III), which is reduced with SnCl2 in refluxing ethanol yielding the corresponding aniline (IV).The condensation of (IV) with trans-3-ethoxypropenoyl chloride in anhydrous pyridine affords the anilide (VI), which is finally cyclized by means of 98% H2SO4.

参考文献中间体

合成目标

【1】 Roberts, D.A.; Campbell, S.F. (Pfizer Inc.); Quinolone inotropic agents. AU 8543032; EP 0166533; ES 8608874; ES 8801797; JP 1986000082; US 4728653 .
【2】 Alabaster, C.T.; Bell, A.S.; Campbell, S.F.; Ellis, P.; Henderson, C.G.; Morris, D.S.; Roberts, D.A.; Ruddock, K.S.; Samuels, G.M.R.; Stefaniak, M.H.; 2(1H)-Quinolinones with cardiac stimulant activity. 2. Synthesis and biological activities of 6-(N-linked, five-membered heteroaryl) derivatives. J Med Chem 1989, 32, 3, 575-83.
【3】 Prous, J.; Castaner, J.; NANTERINONE < Prop INN>. Drugs Fut 1989, 14, 4, 328.

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)	20612	4-Fluoro-2-methyl-1-nitrobenzene; 2-Nitro-5-fluorotoluene	446-33-3	C₇H₆FNO₂	详情	详情
(II)	20613	2,4-dimethyl-1H-imidazole	930-62-1	C₅H₈N₂	详情	详情
(III)	20614	2,4-dimethyl-1-(3-methyl-4-nitrophenyl)-1H-imidazole		C₁₂H₁₃N₃O₂	详情	详情
(IV)	20615	4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylaniline; 4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylphenylamine		C₁₂H₁₅N₃	详情	详情
(V)	20616	(E)-3-ethoxy-2-propenoyl chloride	99471-66-6	C₅H₇ClO₂	详情	详情
(VI)	20617	(E)-N-[4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylphenyl]-3-ethoxy-2-propenamide		C₁₇H₂₁N₃O₂	详情	详情

Extended Information