Name: 3663-35-2|4-Ethyl-2-nitroaniline|97%
Brand: Ambeed
SKU: A577533
Rating: 95 (26 reviews)

1
[ 50-69-1 ]
[ 3663-35-2 ]
D-ribose-(4-ethyl-2-nitro-phenylimine) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol; sulfuric acid

Reference： [1]Aposhian; Lambooy [Journal of the American Chemical Society, 1954, vol. 76, p. 1307]

2
[ 3663-35-2 ]
[ 2001-17-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; acetic acid; sodium nitrite anschliessend Behandeln mit Kupfer(I)-chlorid und konz. wss. Salzsaeure;

Reference： [1]Lambooy [Journal of the American Chemical Society, 1958, vol. 80, p. 110,112]

3
[ 3663-35-2 ]
[ 7369-50-8 ]

Reference： [1]Bulletin de la Societe Chimique de France,1894,vol. <3> 11,p. 210
Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1894,vol. 118,p. 424
[2]Journal of Medicinal Chemistry,1968,vol. 11,p. 580 - 582

4
[ 3663-35-2 ]
[ 1124-38-5 ]

Reference： [1]Journal of the American Chemical Society,1952,vol. 74,p. 1087

5
[ 3663-33-0 ]
[ 3663-35-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium hydroxide In ethanol; water at 80℃; for 5h;
	With sulfuric acid
	With hydrogenchloride

	(hydrolysis);
	Stage #1: N-(4-ethyl-2-nitrophenyl)acetamide With hydrogenchloride; ethanol; water for 12h; Heating / reflux; Stage #2: With sodium hydrogencarbonate In ethanol; water	180.2 Intermediate 180.1 (413 mg) in EtOH/water/conc. HCl (3:4:1) was refluxed for 12 h, then was diluted with EtOAc. The aqueous layer was made basic with sat. NaHCO3, then the layers were separated. The organic phase was washed with water and brine, dried (Na2SO4) and concentrated to afford 317 mg of Intermediate 180.2 as a brown/orange solid.
15.85 g	With sodium hydroxide; water In 1,2-dichloro-ethane at 45 - 97℃; for 5h;

Reference： [1]Wang, Xiaoyu; Zhao, Rui; Ji, Wenming; Zhou, Jie; Liu, Quan; Zhao, Linxiang; Shen, Zhufang; Liu, Shuainan; Xu, Bailing [ACS Medicinal Chemistry Letters, 2022, vol. 13, # 1, p. 118 - 127]
[2]Kondo; Uyeo [Chemische Berichte, 1937, vol. 70, p. 1087,1091] Uyeo [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1937, vol. 57, p. 839,846][Chemisches Zentralblatt, 1938 704]
[3]Paucksch [Chemische Berichte, 1884, vol. 17, p. 768]
[4]Bebawi,G.M.; Lambooy,J.P. [Journal of Medicinal Chemistry, 1968, vol. 11, p. 580 - 582]
[5]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2006/211720, 2006, A1 Location in patent: Page/Page column 83
[6]Buszek, Keith R.; Brown, Neil; Luo, Diheng [Organic Letters, 2009, vol. 11, # 1, p. 201 - 204]

6
[ 50321-08-9 ]
[ 3663-35-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide

Reference： [1]Lambooy; Haley [Journal of the American Chemical Society, 1952, vol. 74, p. 1087]

7
[ 3663-35-2 ]
[ 56-81-5 ]
[ 103860-51-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; orthoarsenic acid at 140℃;

Reference： [1]Case et al. [Journal of Organic Chemistry, 1957, vol. 22, p. 390,392, 393]

8
[ 5460-29-7 ]
[ 3663-35-2 ]
[ 848589-59-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine at 120℃;
	With triethylamine at 120℃;

Reference： [1]Zeng, Lei; Li, Jiaming; Muller, Michaela; Yan, Sherry; Mujtaba, Shiraz; Pan, Chongfeng; Wang, Zhiyong; Zhou, Ming-Ming [Journal of the American Chemical Society, 2005, vol. 127, # 8, p. 2376 - 2377]
[2]Current Patent Assignee: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI - WO2006/83692, 2006, A2 Location in patent: Page/Page column 64

9
[ 3663-35-2 ]
N-(4-ethyl-2-nitrophenyl)propane-1,3-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Et₃N / 120 °C 2: NH₂NH₂*H₂O / ethanol / 6 h / Heating

Reference： [1]Zeng, Lei; Li, Jiaming; Muller, Michaela; Yan, Sherry; Mujtaba, Shiraz; Pan, Chongfeng; Wang, Zhiyong; Zhou, Ming-Ming [Journal of the American Chemical Society, 2005, vol. 127, # 8, p. 2376 - 2377]

10
[ 3663-35-2 ]
[ 96548-25-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1) NaNO₂, conc. hydrochloric acid, 2) CuCl / 1) water, acetone, 5 deg C, 2) 5 deg C 2: 75 percent / H₂ / sulfided Pt/C / aq. HCl; methanol / 3 h / 2699.3 Torr

Reference： [1]McCord, Tommy J.; Warner, Michael R.; Shafer, Paul L.; Davis Disher, Rose M.; Davis, Alvie L. [Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 141 - 144]

11
[ 3663-35-2 ]
[ 109097-05-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetic acid; sulfuric acid; sodium nitrite / anschliessend Behandeln mit Kupfer(I)-chlorid und konz. wss. Salzsaeure 2: pyridine

Reference： [1]Lambooy [Journal of the American Chemical Society, 1958, vol. 80, p. 110,112]

12
[ 3663-35-2 ]
[ 62442-69-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: acetic acid; sulfuric acid; sodium nitrite / anschliessend Behandeln mit Kupfer(I)-chlorid und konz. wss. Salzsaeure 2: pyridine 3: platinum; aqueous acetic acid / beim anschliessenden Behandlung der Reaktionsloesung mit Alloxan unter Zusatz von H₃BO₃

Reference： [1]Lambooy [Journal of the American Chemical Society, 1958, vol. 80, p. 110,112]

13
[ 3663-34-1 ]
[ 3663-35-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetic acid; nitric acid 2: concentrated hydrochloric acid
	Multi-step reaction with 2 steps 1: water; sulfuric acid; nitric acid 2: aqueous sulfuric acid
	Multi-step reaction with 2 steps 1: (nitration) 2: (hydrolysis)

Multi-step reaction with 2 steps 1: acetic acid; acetic anhydride; nitric acid / 1.5 h 2: potassium hydroxide / water; ethanol / 5 h / 80 °C

Reference： [1]Paucksch [Chemische Berichte, 1884, vol. 17, p. 768]
[2]Kondo; Uyeo [Chemische Berichte, 1937, vol. 70, p. 1087,1091] Uyeo [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1937, vol. 57, p. 839,846][Chemisches Zentralblatt, 1938 704]
[3]Bebawi,G.M.; Lambooy,J.P. [Journal of Medicinal Chemistry, 1968, vol. 11, p. 580 - 582]
[4]Wang, Xiaoyu; Zhao, Rui; Ji, Wenming; Zhou, Jie; Liu, Quan; Zhao, Linxiang; Shen, Zhufang; Liu, Shuainan; Xu, Bailing [ACS Medicinal Chemistry Letters, 2022, vol. 13, # 1, p. 118 - 127]

14
[ 3663-35-2 ]
[ 104216-01-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: arsenic acid; aqueous sulfuric acid / 140 °C 2: platinum / Hydrogenation
	Multi-step reaction with 2 steps 1: hydrogenchloride; chloranil / butan-1-ol; water / 2 h / 113 °C / Inert atmosphere; Glovebox; Schlenk technique 2: palladium on activated charcoal; hydrogen / methanol / 24 h / 20 °C / Schlenk technique; Sealed tube

Reference： [1]Case et al. [Journal of Organic Chemistry, 1957, vol. 22, p. 390,392, 393]
[2]Rösener, Thomas; Hoffmann, Alexander; Herres-Pawlis, Sonja [European Journal of Inorganic Chemistry, 2018, vol. 2018, # 27, p. 3164 - 3175]

15
[ 123-91-1 ]
[ 589-16-2 ]
[ 3663-35-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; nitric acid; acetic anhydride	13.a 7-Bromo-5-ethyl-4-oxo-1,4-dihydroquinoline-2-carboxlic acid a) To acetic anhydride (160 ml) at room temperature was added 4-ethylaniline (30 g) over 15 minutes with stirring. The mixture was cooled to 10° C. and concentrated nitric acid (45 ml) was added very slowly, keeping the reaction temperature to below 14° C. The mixture was warmed to room temperature over one hour, poured into ice-water and the resultant yellow solid was filtered off and dried. This was added to dioxan (100 ml), followed by 6M hydrochloric acid (100ml), the solution heated to 70° C. for 3 hr, poured into water, and 1M sodium hydroxide added until pH 10. The product was extracted into ethyl acetate which was then washed with water, brine, dried over magnesium sulphate and solvent removed under vacuum to give 4-ethyl-2-nitroaniline (28.4 g). δ (60 MHz CDCl3) 1.2 (3H, t, CH3), 2.5 (2H, q, CH2). 6.3 (2H. bs, NH2) and 6.6 to 7.8 (3H, m, ArH).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5270309, 1993, A

16
[ 3663-35-2 ]
[ 123158-65-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With bromine; acetic acid at 20℃; for 1h;	15 Add liquid bromine (6g, 37.54mmol) to glacial acetic acid (25mL) and stir for 10min at room temperature. Compound 34-1 (5.5g, 32.86mmol) was dissolved in glacial acetic acid (25mL), and the glacial acetic acid solution of liquid bromine was added dropwise at room temperature. A large amount of yellow solid precipitated during the dropping, and it was stirred for 1 hour at room temperature. TLC monitors the reaction. After the raw materials were reacted, the reaction solution was poured into ice water (100 mL) and stirred for 30 min. After suction filtration, the filter cake was washed with water and dried to obtain compound 34-2 (7.8 g) as a pale yellow solid with a yield of 97%.
	With bromine In acetic acid	13.b 7-Bromo-5-ethyl-4-oxo-1,4-dihydroquinoline-2-carboxlic acid b) To a solution of 4-ethyl-2-nitroaniline (28 g) in acetic acid (250 ml) was added bromine (9.64 ml) dropwise with stirring at room temperature. The reaction mixture was stirred for 1 hour, poured into water, and extracted with ethyl acetate (3200 ml). The organic layer was washed with water (3200 ml), brine (2*100 ml), dried over magnesium sulphate and evaporated to yield 2-bromo-4-ethyl-6-nitroaniline (38 g).
	With hydrogen bromide; bromine In water	17 EXAMPLE 17 EXAMPLE 17 5-Ethyl-7-bromo-4-[benzenesulfonimide]-1,4-dihydroquinoline-2-carboxylic acid, ethyl ester STR24 Mix 4-ethyl-2-nitroaniline (16.6g, 0.1mol) in water (400mL) and add 48% hydrobromic acid (1kg). Add bromine (16g, 0.1mol) with stirring and stir for 1 hour. Dilute to 2L and cool to 7° C. Filter, wash with water and dry to give 4-ethyl-2-nitro-6-bromoaniline.

Reference： [1]Current Patent Assignee: CHINA PHARMACEUTICAL UNIVERSITY - CN111440146, 2020, A Location in patent: Paragraph 0140; 0142-0143
[2]Current Patent Assignee: MERCK & CO INC - US5270309, 1993, A
[3]Current Patent Assignee: SANOFI - US5606063, 1997, A

17
[ 3663-35-2 ]
[ 123158-72-5 ]

Yield	Reaction Conditions	Operation in experiment
	With N-chloro-succinimide In hexane; chloroform; N,N-dimethyl-formamide	27.a 7-Chloro-5-ethyl-4-oxo-1,4-dihydroquinoline-2-carboxylic acid a) To a stirred solution of 4-ethyl-2-nitroaniline (26.3 g, Example 13a) in DMF (100 ml) at -25° C. was added N-chlorosuccinimide (25.4 g) in portions. The mixture was stirred for 1 h at 0° C. and 30 minutes at ambient temperature before evaporation of the solvent under vacuum. Addition of CHCl3 /hexane (1:1) to the residue followed by filtration removed crystalline succinimide. 6-Chloro-4-ethyl-2-nitroaniline (4.6 g) was isolated from the filtrate after chromatography on silica. δ (360 MHz, CDCl3) 1.22 (3H, t, CH3), 2.56 (2H, q, CH2), 6.38 (2H. s, NH2), 7.4 (1H, d, 5-H) and 7.90 (1H, s, 3-H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5270309, 1993, A

18
[ 3663-35-2 ]
[ 4755-77-5 ]
N-ethoxalyl-4-ethyl-2-nitroaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.3 g (90%)	With triethylamine In tetrahydrofuran; ice-water; water	29.a a. a. N-ethoxalyl-4-ethyl-2-nitroaniline To a solution of 0.9 g (5.4 mmol) 4-ethyl-2-nitroaniline in 50 ml dry tetrahydrofuran was added 1.0 ml (7.1 mmol) dry triethylamine and the reaction mixture was cooled in ice-water. 0.8 ml (7.2 mmol) ethyl oxalylchloride in 10 ml dry tetrahydrofuran was added dropwise and the reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was evaporated in vacuo and the residue was stirred with water. The precipitate was filtered off to give 1.3 g (90%) of N-ethoxalyl-4-ethyl-2-nitroaniline. M.p. 110°-112° C.

Reference： [1]Current Patent Assignee: NOVO NORDISK A/S - US5061706, 1991, A

19
[ 3663-35-2 ]
[ 116599-06-5 ]

Yield	Reaction Conditions	Operation in experiment
5.4 g (75.33%)	With hydrogenchloride;palladium-carbon; In ethanol;	(b) Preparation of 4-ethyl-1,2-phenylenediamine A solution of 5.7 g (34.3 m mol) of 4-ethyl-2-nitroaniline in 150 ml of ethanol was hydrogenated at atmospheric pressure over 1.8 g of 5% Pd/C with Ishii's Catalytic Hydrogenation Apparatus with Magnetic Stirrer Model CHA-M. The catalyst was filtered off, and removal of the solvent in vacuo gave an oil (4 g). Then, 6 g (58.8 m mol) of concentrated hydrochloric acid was added to the solution, that gave 5.4 g (75.33%) of 4-ethyl-1,2-phenylenediamine dihydrochloride.

Reference： [1]Patent: US4714764,1987,A

20
[ 3663-35-2 ]
[ 1124-38-5 ]
[ 368-71-8 ]

Yield	Reaction Conditions	Operation in experiment
	palladium on charcoal; In ethanol;	The crude 2-nitro-4-ethylaniline was hydrogenated in 100 ml. of ethanol over 500 mg. of 5 percent palladium on charcoal, until gas uptake ceased. The reaction mixture was filtered and evaporated, yielding 4-ethyl-o-phenylenediamine as a dark oil which solidified overnight. The identity of the product was confirmed by IR. In similar procedures, there was prepared 4-trifluoromethyl-o-phenylenediamine, m.p. 55-57C.

Reference： [1]Patent: US3962440,1976,A

21
[ 3663-35-2 ]
[ 1095636-39-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 4-ethyl-2-nitroaniline With bromine; copper(ll) bromide In acetonitrile at 50℃; for 0.666667h; Stage #2: With tert.-butylnitrite In acetonitrile at 50℃; for 1.5h;

Reference： [1]Buszek, Keith R.; Brown, Neil; Luo, Diheng [Organic Letters, 2009, vol. 11, # 1, p. 201 - 204]

22
[ 1033711-32-8 ]
[ 3663-35-2 ]
C₁₇H₂₀N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid In toluene for 70h; Reflux;	203 4-Ethyl-2-nitroaniline 1.00 g, ethyl 6-(1,3-dioxolan-2-yl)-4-oxohexanoate 1.38 g, p-toluenesulfonic acid monohydride 114 mg and toluene 150 mL were mixed and heated under reflux for 70 hours with Dean-Stark device, and thereafter the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (chloroform) to provide 1.29 g of a brown, viscous substance, to which 20 mL of acetic acid and 8 mL of water were added, followed by addition of 2.35 g of sodium hyposulfite and 3 hours' heating under reflux. The reaction liquid was allowed to cool off, to which 50 g of ice was added and it was made weakly alkaline with 25% aqueous ammonia, and extracted with ethyl acetate. The organic layer was washed with 20 mL of saturated brine, dried over anhydrous magnesium sulfate and from which the solvent was distilled off under reduced pressure. The residue was purified on silica gel chromatography (hexane: ethyl acetate = 1:1) to provide 471 mg of a brown, viscous substance. It was mixed with 178 mg of triphosgene and 10 mL of toluene, and heated under reflux for 14.5 hours. Cooling the reaction liquid off, the precipitate was recovered by filtration, washed with ethyl acetate and dried under reduced pressure to provide 277 mg of the title compound. 1H-NMR(DMSO-d6, δ): 1.1-1.3(6H, m), 2.65(2H, q, J=7.5Hz), 2.82(2H, t, J=7.3Hz), 3.45(2H, t, J=7.3Hz), 4.10(2H, q, J=7.2Hz), 6.42(1H, d, J=4.2Hz), 6.98(1H, d, J=4.2Hz), 7.06(1H, dd, J=1.9, 8.9Hz), 7.16(1H, d, J=1.9Hz), 7.93(1H, d, J=8.9Hz), 11.14(1H, br s). MS(m/z): 312 (M+), 225(base).

Reference： [1]Current Patent Assignee: ASKA PHARMACEUTICAL CO., LTD. - EP2103613, 2009, A1 Location in patent: Page/Page column 121

23
[ 589-16-2 ]
[ 3663-35-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: 4-aminoethylbenzene With trifluoroacetic anhydride In dichloromethane at 0℃; for 0.25h; Reflux; Inert atmosphere; Glovebox; Schlenk technique; Stage #2: With nitric acid In dichloromethane at 0℃; for 3h; Reflux; Inert atmosphere; Glovebox; Schlenk technique;
	Stage #1: 4-aminoethylbenzene With acetic anhydride at 0 - 20℃; for 0.5h; Stage #2: With nitric acid In water at 0℃; for 0.5h;	A 4-Ethylaniline (15.0 g, 124 mmol) was carefully added to acetic anhydride (100 mL, 1.06 mol) that was pre-cooled to 0 °C5 and the mixture was warmed to rt over 30 min, then recooled to 0 °C, and nitric acid (7.90 mL of a 70% v/v aq. solution, 124 mL) was added dropwise. After 30 min, the reaction mixture was quenched into an ice-water bath, the resulting slurry was filtered, and the filter cake was dried in vacuo. The crude solid product was dissolved in 6M HCl (100 mL) and dioxane (60 mL), and the resulting mixture was heated at 0 °C. After 3 h, the reaction mixture was cooled to rt and concentrated in vacuo. The crude residue was suspended in EtOAc and neutralized via addition of 6N NaOH. The layers were separated, and the aq. layer was extracted with EtOAc. The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound, i-6a. m/∑ (ES) 167 (MH)+.
3.3 g	Stage #1: 4-aminoethylbenzene With acetic anhydride In 1,2-dichloro-ethane at 80℃; for 1h; Stage #2: With nitric acid In 1,2-dichloro-ethane at 45 - 50℃;	27.27.1 27.1 4-Ethyl-2-nitroaniline 27.1 4-Ethyl-2-nitroaniline A 100 mL round-bottom flask was charged with acetic anhydride (3.39 g) and 1,2-dichloroethane (30 mL), p-ethylaniline (3.5 g) was then added, and the mixture was stirred at 80°C for 1 h. The reaction solution was cooled to 50°C, fuming nitric acid (4.37 g) was slowly added dropwise thereto, and the resulting mixture was stirred at 45°C for 1 h. Sodium hydroxide (3.76 g) was dissolved in a minimum amount of water and added to the reaction solution within 10 minutes. The temperature was raised to 80°C or higher, and 1,2-dichloroethane was distilled out of the reaction system. When the reaction temperature rose to between 95°C and 97°C, stirring was continued for 16 h. A sample was taken and subjected to LC-MS detection, and a peak of the product (167.0[M+1]+) was detected. The reaction solution was cooled to room temperature, diluted with 50 mL of water, and extracted with ethyl acetate (50 mL * 4). The organic phases were washed with saturated saline (30 mL), dried over anhydrous sodium sulfate and filtered, and the solvent was distilled off under reduced pressure, so as to obtain 3.3 g of 4-ethyl-2-nitroaniline. MS(ESI)m/z 167.0[M+1]+.

Multi-step reaction with 3 steps 1: pyridine / ethyl acetate / 3 h / 20 °C 2: acetic acid; acetic anhydride; nitric acid / 1.5 h 3: potassium hydroxide / water; ethanol / 5 h / 80 °C

Reference： [1]Rösener, Thomas; Hoffmann, Alexander; Herres-Pawlis, Sonja [European Journal of Inorganic Chemistry, 2018, vol. 2018, # 27, p. 3164 - 3175]
[2]Current Patent Assignee: MERCK & CO INC - WO2011/5608, 2011, A1 Location in patent: Page/Page column 36
[3]Current Patent Assignee: NANJING GEAR PHARMA TECH; SINO BIOPHARMACEUTICAL LIMITED - EP3689860, 2020, A1 Location in patent: Paragraph 0367; 0368
[4]Wang, Xiaoyu; Zhao, Rui; Ji, Wenming; Zhou, Jie; Liu, Quan; Zhao, Linxiang; Shen, Zhufang; Liu, Shuainan; Xu, Bailing [ACS Medicinal Chemistry Letters, 2022, vol. 13, # 1, p. 118 - 127]

24
[ 3663-35-2 ]
[ 1261225-72-2 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; silver sulfate In ethanol at 20℃; for 1.5h;	B Compound i-6a (7.00 g, 42.1 mmol) was added to a stirred solution of iodine (10.7 g, 42.1 mmol) and silver sulfate (13.1 g, 42.1 mmol) in EtOH (150 mL), and the resulting mixture was allowed to stir at rt. After 90 min, the reaction mixture was filtered through a short column of Celite, eluting copiously with EtOH. The organics were concentrated in vacuo, and the crude residue was partitioned between EtOAc and IN NaOH. The layers were separated, and the organics were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The resulting crude residue was purified by column chromatography on silica gel (gradient elution, 0- 25% EtOAc/hexanes as eluent) to afford the title compound l^b. m/z (ES) 293 (MH)+.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2011/5608, 2011, A1 Location in patent: Page/Page column 36

25
4-chloro-6-methylpyrimidine-5-carbonitrile [ No CAS ]
[ 3663-35-2 ]
4-[(4-ethyl-2-nitrophenyl)amino]-6-methylpyrimidine-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	In neat (no solvent) at 130℃; for 0.5h;

Reference： [1]Basetti, Vishnu; Pallepati, Rangarao; Thadi, Emima; Hosahalli, Subramanya; Potluri, Vijay [Heterocyclic Communications, 2014, vol. 20, # 4, p. 207 - 214]

26
[ 18799-32-1 ]
[ 3663-35-2 ]
C₂₀H₂₃N₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18 g	Stage #1: 4-ethyl-2-nitroaniline With hydrogenchloride In water at 20℃; for 0.5h; Stage #2: With sodium nitrite In water at 0 - 5℃; for 2h; Stage #3: N-(2-cyanoethyl)-N-(2-methoxyethyl)aniline With sulfuric acid In water at 0 - 70℃; for 5h;	Preparation of compound B1 (1) adding water to250mL three-necked flask 100 grams 2-nitro-4- Ethylaniline 8.3 g, 36% mass%concentration of hydrochloric acid of 20 g, was stirred for 0.5 hours at roomtemperature, Ice cooling to 0-5 ° C, was added dropwise mass fraction of 20%solution of 17.8 g of sodium nitrite, and then continue to The reaction for 2hours at 0-5 ° C, then 0.5 g amino acids, potassium iodide starch paper test noAfter the color, to obtain a diazonium salt to be coupled. [2] 1000mL beaker wasadded 200 grams of water, 6 g of concentrated sulfuric acid, N- cyanoethyl -N-methoxy 10.5 g ethyl aniline dissolved with stirring, maintained at 0-5 ° Csolution of step (1) to give the diazo Salt, and reacted at this temperaturefor 3 hours, warmed to 65-70 ° C for 2 hours, filtered to give the intermediateProduct cake, a dry goods product cake was 18 g.
18 g	Stage #1: 4-ethyl-2-nitroaniline With hydrogenchloride In water at 20℃; for 0.5h; Stage #2: With sodium nitrite In water at 0 - 5℃; for 2h; Stage #3: N-(2-cyanoethyl)-N-(2-methoxyethyl)aniline Further stages;	1; 2 Preparation of Compound B1 (1) In a 250 ml three-mouth flask, add 100 g water, 2-nitro-4-ethylaniline 8.3 g, mass percentage concentration of 36% hydrochloric acid 20 g. Stir at room temperature for 0.5 hours. Add ice and cool to 0-5 °C. Drop mass fraction 20% sodium nitrite solution 17.8 g. Then continue at 0-5 °C react for 2 hours, then add 0.5 g sulfamic acid. After potassium iodide starch paper tests colorless, to get the diazonium salt to be coupled.(2) In a 1000 ml beaker, add 200 g water, concentrated sulfuric acid 6 g, N-cyanoethyl-N-methoxyethylaniline 10.5 g. After stirring to dissolve, maintain at 0-5 °C drop step (1) obtained diazonium salt, and maintain the temperature reaction 3 hours. Increase temperature to 65-70 °C maintain temperature 2 hours, filtered to obtain the intermediate product filter cake, folding dry product filter cake 18 g.
18 g	Stage #1: 4-ethyl-2-nitroaniline With hydrogenchloride In water at 20℃; for 0.5h; Stage #2: With sodium nitrite In water at 0 - 5℃; for 2h; Stage #3: N-(2-cyanoethyl)-N-(2-methoxyethyl)aniline With sulfuric acid In water at 0 - 75℃; for 5h;	Preparation of compound B1 (1) in 250mL three-necked flask was added 100g of water,8.3 g of 2-nitro-4-ethylaniline, 20 g of hydrochloric acid with a mass percentage concentration of 36%, stirring at room temperature for 0.5 hour,Add ice cooling to 0-5 ° C, 17.8 g mass fraction of 20% sodium nitrite solution, and then continue at 0-5 ° C for 2 hours, then add 0.5 g amino acid, potassium iodide test paper to test colorless After that, to obtain diazonium salt to be coupled.(2) In a 1000mL beaker was added 200 grams of water, 6 grams of concentrated sulfuric acid,N-cyanoethyl-N-methoxyethylaniline 10.5 g, after stirring to dissolve,Keeping the diazonium salt obtained in the step (1) dropwise at 0-5 ° C, keeping the temperature at this temperature for 3 hours, raising the temperature to 65-70 ° C for 2 hours, filtering to obtain the intermediate product cake, 18 grams.

18 g

Stage #1: 4-ethyl-2-nitroaniline With hydrogenchloride In water at 20℃; for 0.5h; Stage #2: N-(2-cyanoethyl)-N-(2-methoxyethyl)aniline With sulfuric acid In water at 0 - 5℃; for 2h;

1; 2 Preparation of Compound B1: (1) 100 g of water was added to a 250 mL three-necked flask,2-nitro-4-ethylaniline 8.3 g,20% hydrochloric acid with a mass concentration of 36%,Stir at room temperature for 0.5 hours.Add ice to cool down to 0-5 ° C,Add 17.8 grams of sodium nitrite solution with a mass fraction of 20%.Then continue to react at 0-5 ° C for 2 hours.Then add 0.5 grams of sulfamic acid,After testing for colorlessness with starch potassium iodide test paper,That is, the diazonium salt is obtained for coupling. (2) Add 200 grams of water to a 1000 mL beaker,6 grams of concentrated sulfuric acid,N-cyanoethyl-N-methoxyethylaniline 10.5 g,After stirring and dissolving,Keeping the diazonium salt obtained in the step (1) dropwise at 0-5 ° C,And the reaction was kept at this temperature for 3 hours.Warm up to 65-70 ° C for 2 hours,Filtered the intermediate product filter cake,Dry the product filter cake 18 grams.

Reference： [1]Current Patent Assignee: SHANGHAI ANOKY GROUP CO., LTD. - CN104341791, 2016, B Location in patent: Paragraph 0126; 0127
[2]Current Patent Assignee: SHANGHAI ANOKY GROUP CO., LTD. - CN104710813, 2017, B Location in patent: Paragraph 0126; 0127
[3]Current Patent Assignee: SHANGHAI ANOKY GROUP CO., LTD. - CN104710836, 2017, B Location in patent: Paragraph 0126; 0127
[4]Current Patent Assignee: SHANGHAI ANOKY GROUP CO., LTD. - CN104710810, 2018, B Location in patent: Paragraph 0126; 0127

27
[ 67-56-1 ]
[ 3663-35-2 ]
6-ethylbenzimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water at 190℃; Inert atmosphere;	24 In a fixed-bed reactor with an internal diameter of 10mm,The Cu3wt%_Pd5wt%-Mg2wt%/Al203 catalyst obtained in Example 2 was charged into a constant temperature zone of the reaction tube.Both ends are filled with quartz sand and quartz wool.To ensure a stable and even distribution of the reaction gas stream.Sealing means,The catalyst was reductively activated with hydrogen (25 ml/min) at 250°C for 9 hours.Then change the carrier gas to nitrogen,And adjust the nitrogen flow to 100ml/h and pressure to 4MPa,Then adjust the temperature to 190 °C; use high pressure pump to o-nitroaniline compound: Methanol: Distilled water was continuously fed at a mass ratio of 1:20:12 to start the reaction. The flow rate of the mixture of o-nitroaniline compounds, methanol, and distilled water was 1.2 g/h. The reaction product passesAfter the condenser was cooled and entered the gas-liquid separator, the liquid product was collected. The results of the experiment are shown in Table 3.

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN105037274, 2018, B Location in patent: Paragraph 0064-0068

28
[ 3663-35-2 ]
N-(6-ethylquinolin-8-yl)-1,3-dimethylimidazolidin-2-imine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: hydrogenchloride; chloranil / butan-1-ol; water / 2 h / 113 °C / Inert atmosphere; Glovebox; Schlenk technique 2.1: palladium on activated charcoal; hydrogen / methanol / 24 h / 20 °C / Schlenk technique; Sealed tube 3.1: acetonitrile / 80 °C / Schlenk technique; Inert atmosphere; Glovebox 3.2: 12 h / Schlenk technique; Inert atmosphere; Glovebox 3.3: 2 h / Schlenk technique; Inert atmosphere; Glovebox

Reference： [1]Rösener, Thomas; Hoffmann, Alexander; Herres-Pawlis, Sonja [European Journal of Inorganic Chemistry, 2018, vol. 2018, # 27, p. 3164 - 3175]

29
[ 3663-35-2 ]
2-(6-ethylquinolin-8-yl)-1,1,3,3-tetramethylguanidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: hydrogenchloride; chloranil / butan-1-ol; water / 2 h / 113 °C / Inert atmosphere; Glovebox; Schlenk technique 2.1: palladium on activated charcoal; hydrogen / methanol / 24 h / 20 °C / Schlenk technique; Sealed tube 3.1: acetonitrile / 80 °C / Schlenk technique; Inert atmosphere; Glovebox 3.2: 12 h / Schlenk technique; Inert atmosphere; Glovebox 3.3: 2 h / Schlenk technique; Inert atmosphere; Glovebox

Reference： [1]Rösener, Thomas; Hoffmann, Alexander; Herres-Pawlis, Sonja [European Journal of Inorganic Chemistry, 2018, vol. 2018, # 27, p. 3164 - 3175]

30
[ 3663-35-2 ]
[ 107-02-8 ]
[ 103860-51-1 ]

Yield	Reaction Conditions	Operation in experiment
58%	With hydrogenchloride; chloranil In water; butan-1-ol at 113℃; for 2h; Inert atmosphere; Glovebox; Schlenk technique;

Reference： [1]Rösener, Thomas; Hoffmann, Alexander; Herres-Pawlis, Sonja [European Journal of Inorganic Chemistry, 2018, vol. 2018, # 27, p. 3164 - 3175]

31
[ 3663-35-2 ]
4-ethyl-1-iodo-2-nitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.2 g	Stage #1: 4-ethyl-2-nitroaniline With hydrogenchloride In water at 100℃; for 0.166667h; Stage #2: With sodium nitrite In water at 0℃; for 0.5h; Stage #3: With potassium iodide In water at 0 - 70℃; for 2h;	27.27.2 27.2 4-Ethyl-1-iodo-2-nitrobenzene 27.2 4-Ethyl-1-iodo-2-nitrobenzene 4-Ethyl-2-nitroaniline (1.6 g) was dissolved in concentrated hydrochloric acid (3.2 mL) and the mixture was stirred at 100°C for 10 min. The reaction solution was cooled to 0°C, and a solution of sodium nitrite (0.798 g) in water (3.2 mL) was added thereto. The reaction solution was stirred at 0°C for 30 min. The reaction mixture was slowly added to a solution of potassium iodide (2.4 g) in water (2.5 mL) at 0°C. The resulting mixture was stirred at 70°C for 2 h. A sample was taken, and TLC detection showed that the spots of the raw materials disappeared. The reaction solution was diluted with 80 mL of water and extracted with ethyl acetate (80 mL * 3). The organic layer was washed with saturated sodium sulfite solution (50 mL) and saturated saline (50 mL). The obtained organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was distilled off under reduced pressure, and the resulting mixture was subjected to silica gel column chromatography, so as to obtain 2.2 g of 4-ethyl-1-iodo-2-nitrobenzene.

Reference： [1]Current Patent Assignee: NANJING GEAR PHARMA TECH; SINO BIOPHARMACEUTICAL LIMITED - EP3689860, 2020, A1 Location in patent: Paragraph 0367; 0369

32
[ 3663-35-2 ]
3-((2-ethoxycarbonyl)-5-ethyl-7-nitro-1H-indol-3-yl)propanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium nitrite; hydrogenchloride / water / 0 °C 1.2: 1.25 h 1.3: 0.17 h / Reflux 2.1: 4 h / 80 °C