Home Cart 0 Sign in  
X

[ CAS No. 1635-61-6 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type HazMat fee for 500 gram (Estimated)
Excepted Quantity USD 0.00
Limited Quantity USD 15-60
Inaccessible (Haz class 6.1), Domestic USD 80+
Inaccessible (Haz class 6.1), International USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic USD 100+
Accessible (Haz class 3, 4, 5 or 8), International USD 200+
3d Animation Molecule Structure of 1635-61-6
Chemical Structure| 1635-61-6
Chemical Structure| 1635-61-6
Structure of 1635-61-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 1635-61-6 ]

Related Doc. of [ 1635-61-6 ]

Alternatived Products of [ 1635-61-6 ]

Product Details of [ 1635-61-6 ]

CAS No. :1635-61-6 MDL No. :MFCD00007776
Formula : C6H5ClN2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :ZCWXYZBQDNFULS-UHFFFAOYSA-N
M.W : 172.57 Pubchem ID :74218
Synonyms :

Calculated chemistry of [ 1635-61-6 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 44.68
TPSA : 71.84 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.42 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.24
Log Po/w (XLOGP3) : 2.72
Log Po/w (WLOGP) : 2.36
Log Po/w (MLOGP) : 0.79
Log Po/w (SILICOS-IT) : 0.03
Consensus Log Po/w : 1.43

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.96
Solubility : 0.189 mg/ml ; 0.00109 mol/l
Class : Soluble
Log S (Ali) : -3.88
Solubility : 0.0226 mg/ml ; 0.000131 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.51
Solubility : 0.535 mg/ml ; 0.0031 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.59

Safety of [ 1635-61-6 ]

Signal Word:Danger Class:6.1
Precautionary Statements:P260-P262-P264-P270-P271-P273-P280-P284-P301+P310+P330-P302+P352+P310-P304+P340+P310-P314-P361+P364-P391-P403+P233-P405-P501 UN#:2237
Hazard Statements:H300+H310+H330-H373-H411 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1635-61-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1635-61-6 ]

[ 1635-61-6 ] Synthesis Path-Downstream   1~93

  • 1
  • [ 611-06-3 ]
  • [ 1635-61-6 ]
YieldReaction ConditionsOperation in experiment
261.2 g With ammonia; at 90 - 140℃; under 7500.75 - 60006 Torr; for 4h;Autoclave; In a magnetic stirring autoclave, 339.2 g (99.1%, 1.75 mol) of <strong>[611-06-3]2,4-dichloronitrobenzene</strong> was added, and the autoclave was sealed, stirring was started, then 134.9 g (99.5%, 7.9 mol) of liquid ammonia was introduced, and the temperature was raised to 90 C by heating, the heating was stopped, after the temperature was stable, the temperature was controlled to 120~135 C, the pressure was 1.0~8.OMPa, the final temperature does not exceed 140 C, the reaction was about 4 hours, and the pressure was released to normal pressure. In addition, 600 g of water was added in a 2000 ml beaker, and the mixture was heated to 50 to 70 C with stirring. After the pressure relief of the high pressure reactor was completed, the material was transferred to water while stirring, stirred for half an hour, suction filtered, and the filter cake was dried to obtain a dark yellow solid powder 308.2 g, a melting point of 117 to 119 C, then subject to methanol crystallization and purification, and drying, to obtain a yellow needle crystals 261.2 g, the melting point was 126.8 C, the content was 98.6%, and the molar yield was 85.27%.
  • 3
  • [ 1635-61-6 ]
  • [ 160938-18-1 ]
YieldReaction ConditionsOperation in experiment
With potassium iodide; sodium nitrite; In hydrogenchloride; water; ethyl acetate; REFERENCE EXAMPLE 1 1-nitro-2-iodo-4-chlorobenzene To a suspension of 2-nitro-5-chloroaniline (5.00 g) in conc. hydrochloric acid (30 ml) under cooling with ice, was added a solution of sodium nitrite (2.10 g) in water (10 ml) dropwise and the mixture was stirred for 30 minutes. Under cooling with ice, to this solution was added a solution of potassium iodide (5.30 g) in water (20 ml) dropwise and the mixture was stirred for 1 hour at room temperature. The solid that appeared was collected by filtration and was dissolved in ethyl acetate and was dried and concentrated to give a crude product of the title compound. It was purified by recrystallization from ethyl acetate-hexane to give the title compound having the following physical data (5.14 g, yellow powder). TLC: Rf 0.69 (n-hexane:ethyl acetate=9:1); NMR(CDCl3): delta 8.06 (d, J=2.2 Hz, 1H), 7.85 (d, J=8.6 Hz, 1H), 7.47 (dd, J=8.6, 2.2 Hz, 1H).
  • 4
  • [ 108-42-9 ]
  • [ 825-41-2 ]
  • [ 1635-61-6 ]
  • 5
  • [ 110-91-8 ]
  • [ 1635-61-6 ]
  • [ 54998-00-4 ]
YieldReaction ConditionsOperation in experiment
95% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 12h; Inert atmosphere;
95% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 12h; Inert atmosphere; 4.6 4.1.6 5-morpholino-2-nitrobenzenamine (11) A mixture of 5-chloro-2-nitrobenzenamine (1g, 1.8 mmol), morpholine (2 ml) and dry K2CO3 (1.2 g, 9 mmol) were taken along with 5 ml of dry DMF and heated at 110 °C under nitrogen atmosphere for 12 h. The reaction mixture was then dried under vacuum and 50 ml of cold water was added to it to form a yellow colored precipitate which was filtered off and washed several times with distilled water and then dried affording the yellow colored product which was adjudged to be pure by TLC (2% MeOH/CHCl3 on pre-coated silica gel) (1.23g, 95%). 1H NMR (400MHz, DMSO-d6) δ ppm 7.82 (d, J=10, 1H), 7.28 (s, 2H), 6.39 (dd, J=9.8, J=2.8, 1H), 6.2 (d, J=2.8, 1H), 3.70 (t, J=4.8, H), 3.27 (t, J=4.8, 4H); IR (KBr): 3448, 3335, 3179, 3088, 2973, 2928, 2872, 2846, 1618, 1234, 1123, 892cm-1; HRMS: m/z=246.0858 [M+Na]+, Calcd.=246.0855 [M+Na]+; mp 188°C.
90% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 24h; 35 Synthesis of 5-morpholine-2-nitroaniline A mixture of 5-chloro-2-nitroaniline (3.00g, 17.4mmol), morpholine (4.54g, 52.2mmol), potassium carbonate (3.60g, 26.1mmol) was reacted at 110°C for 24h in DMF (30mL).After cooling to room temperature, water (300 mL) was added, the solid was collected by filtration, washed with water, and dried to obtain 5-morpholine-2-nitroaniline as a yellow solid (3.49 g, 90%) and put into the next step.
87% for 6h; Heating;
77% In 1-methyl-pyrrolidin-2-one at 100℃; for 1h; Microwave irradiation; 5-Morpholino-2-nitroaniline 62 A solution of 5-chloro-2-nitroaniline (100 mg, 0.58 mmol) in NMP (4.5 mL) was treated with morpholine (75 mg, 0.86 mmol) in the presence of triethylamine (0.2 mL, 1.44 mmol) and then the reaction mixture was heated via microwave irradiation to 100 °C for 1 hour. Following cooling, the solvent was removed by vacuum and the resulting crude material was purified by flash column chromatography afforded the title compound in a 77% yield. 1H NMR: (400 MHz, DMSO-d6): δ 7.82 (d, 1H, J = 9.6 Hz), 7.29 (bs, 2H), 6.39 (dd, 1H, J = 2.8 and 9.6 Hz), 6.22 (d, 1H, J = 2.4 Hz), 3.70 (m, 4H), 3.27 (m, 4H).
75% With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 6h; A mixture of 5-cholro-2-nitroaniline (8, 172 mg, 1 mmol), morpholine(87 mg, 1 mmol) and potassium carbonate (552 mg,4 mmol) in DMF (5 mL) was heated at 100° C for 6 h and then cooled to room temperature. After addition of 20 mL ofwater, the resulting precipitate was filtered and the obtained solid was suspended in 25 mL of 2N acetic acid and filtered.The filtrate was slightly basified with ammonia solution and the resulting precipitate was filtered off to give compound 9 as a yellow solid.Yield: 167 mg, 75%; mp 125-128° C; 1H NMR (200MHz, CDCl3): 7.93 (d, J = 8.4 Hz, 1H), 6.83 (bs, 2H), 6.18(dd, J = 8.4, 1.9 Hz, 1H), 6.10 (d, J = 8.8 Hz, 1H), 3.50-4.00(m, 4H), 2.40-2.50 (m, 4H); MS (EI) m/z 223 [M]+.4.2.5.
75% With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 6h; 2-Amino-4-morpholinonitrobenzene (9b) To a mixture of 5-chloro-2-nitroaniline (8, 172 mg, 1mmol), morpholine (87 mg, 1 mmol) and potassium carbonate (552 mg, 4 mmol) were heated in DMF (5 mL) at 100°C for 6 h and then cooled to room temperature. After addition of water (20 mL), the resulting precipitates were filtered andthe obtained solid was suspended in 2 N acetic acid (25mL) and filtered. The filtrate was slightly basified with ammonia solution and the resulting precipitate was filtered to give the compound 9b as a yellow solid. Yield: 167 mg,75%; mp 125-128 °C; 1H NMR (200 MHz CDCl3): 7.93 (d,J = 8.4 Hz, 1H), 6.83 (bs, 2H), 6.14-6.22 (dd, J = 8.4, 1.9Hz, 1H), 6.10 (d, J = 8.8 Hz, 1H), 3.50-4.00 (m, 4H), 2.40-2.50 (m, 4H); MS (EI) m/z 223 [M]+.
75% With potassium carbonate In N,N-dimethyl-formamide for 3h; Reflux; 2 To a solution of 5-cholro-2-nitroaniline (172 mg, 1 mmol), morpholine (87 mg, 1 mmol) and potassium carbonate (138 mg, 1 mmol) in DMF (5 mL) was heated at reflux for 3h and then cooled to room temperature. After addition of 20 mL of water, the resulting precipitate was filtered and the obtained solid was suspended in 25 mL of 2N acetic acid and filtered. The filtrate was slightly basified with ammonia solution, and the resulting precipitate was filtered off to give the compound Ib (167 mg, 75%) as a yellow solid.1H NMR (200 MHz CDCl3): δ 2.39 (s, 3H), 2.40-2.50 (m, 4H), 3.28-3.48 (m, 4H), 6 10 (d, IH, J= 8.8Hz), 6.15-6.23 (dd, J= 8.4Hz, 1.9Hz, IH), 6.85 (bs, 2H), 7.9 (d, J = 8.4 Hz5IH). MS (EI) 223 [M]+
58% With potassium carbonate In ISOPROPYLAMIDE at 130 - 140℃; Inert atmosphere; 19.A A mixture of 5-chloro-2-nitroaniline (4.0 g, 2.3 mmol), morpholine (3.45 ml, 41 mmol) and anhydrous potassium carbonate (3.2 g, 23 mmol) in N,N-dimethylacetamide (40 ml) was stirred at 130-140 °C under nitrogen overnight. The reaction mixture was then cooled to room temperature, poured onto ice and allowed to stand for 2-3 h. The yellow- brown precipitate was collected by filtration to afford 5-morpholino-2-nitroaniline (3.0 g, 58%), mp 183-185 °C (lit(8) mp 187.5 °C). nmr (500 MHz, CDCI3) 6 3.31, m, 4H, 2 x C¾N; 3.82, m, 4H, 2 x CH20; 5.95, d (J = 2.7 Hz), 1H, H6; 6.16, br, 2H, NH2; 6.27, dd (J = 9.5, 2.7 Hz), 1H, H4; 8.03, d (J 9.8 Hz), 1H, H3. 13C nmr (125 MHz, CDC13) δ 47.3, 2 x CH2N; 66.6, 2 x CH20; 98.7, 105.6, C4, C6; 125.4, C2; 128.5, C3; 147.2, 155.9, CI, C5.
56% With potassium carbonate In N,N-dimethyl-formamide for 24h; Heating;
43% In dimethylsulfoxide (DMSO) 12 5-Morpholin-4-yl-2-nitro-phenylamine EXAMPLE 12 5-Morpholin-4-yl-2-nitro-phenylamine A solution of 5-chloro-2-nitrophenylamine (4.3 g, 25 mmol) and morpholine (4.4 mL, 500 mmol) in dimethylsulfoxide (DMSO) (25 mL) was stirred at 90° C. for 16 h. The reaction mixture was poured into water (500 mL) and the resulting precipitate was collected by vacuum filtration and recrystallized from methanol (300 mL) to yield the product as orange crystals (2.4 g, 43%). M.P. 177-178° C. (lit. 184-186° C.). See, Polymers 36:3401-3408 (1995). 1H NNIR (90 MHz, CDCl3) δ8.02 (d, J=9.2 Hz, 1H), 6.32-6.09 (m, 4H), 3.82 (t, J=5.0 Hz, 4H), 3.29 (t, J=5.0 Hz, 4H). LRMS: 223 (M+).
25.4% In dimethyl sulfoxide at 90℃; for 18h;
With potassium carbonate
With triethylamine In DMF (N,N-dimethyl-formamide) at 120℃; 9 Morpholine (1 equivalent) and 5-chloro-2-nitroaniline (1 equivalent) were dissolved in DMF, and TEA (2 equivalents) was added. The reaction mixture was heated at 120 C overnight. The reaction mixture was then cooled to room temperature, most of the DMF was distilled off, and water was added to the residue to obtain the crude product as a precipitate. The solid was dried and purified by chromatography on silica gel (2-10% MeOH/CH2CI2) to afford the desired product, 5-morpholin-4-yl-2-nitro- phenylamine.
With potassium carbonate In N,N-dimethyl-formamide for 16h; Inert atmosphere;

Reference: [1]Maji, Basudeb; Kumar, Krishan; Kaulage, Mangesh; Muniyappa; Bhattacharya, Santanu [Journal of Medicinal Chemistry, 2014, vol. 57, # 16, p. 6973 - 6988]
[2]Kaulage, Mangesh H.; Maji, Basudeb; Pasadi, Sanjeev; Ali, Asfa; Bhattacharya, Santanu; Muniyappa [European Journal of Medicinal Chemistry, 2018, vol. 148, p. 178 - 194]
[3]Current Patent Assignee: CHINA PHARMACEUTICAL UNIVERSITY - CN112047932, 2020, A Location in patent: Paragraph 0256-0259
[4]Kuznetsov, V. A.; Garabadzhiu, A. V.; Ginzburg, O. F. [Journal of Organic Chemistry USSR (English Translation), 1986, vol. 22, p. 403 - 404][Zhurnal Organicheskoi Khimii, 1986, vol. 22, # 2, p. 455 - 456]
[5]Chen, Ting; Sorna, Venkataswamy; Choi, Susie; Call, Lee; Bearss, Jared; Carpenter, Kent; Warner, Steven L.; Sharma, Sunil; Bearss, David J.; Vankayalapati, Hariprasad [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 24, p. 5473 - 5480]
[6]Kamal, Ahmed; Pogula, Praveen Kumar; Khan, Mohammed Naseer Ahmed; Seshadri, Bobburi Naga; Sreekanth, Kokkonda [Medicinal Chemistry, 2013, vol. 9, # 5, p. 651 - 659]
[7]Kamal, Ahmed; Kumar, Pogula Praveen; Khan, Mohammed Naseer Ahmed; Sheshadri, Bobburi Naga; Srinivas, Olepu [Letters in drug design and discovery, 2015, vol. 12, # 5, p. 374 - 384]
[8]Current Patent Assignee: COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH (IN) - WO2009/110000, 2009, A1 Location in patent: Page/Page column 12
[9]Current Patent Assignee: PETER MACCALLUM CANCER CENTER - WO2011/123890, 2011, A1 Location in patent: Page/Page column 74
[10]Charton, Julie; Girault-Mizzi, Sophie; Debreu-Fontaine, Marie-Ange; Foufelle, Fabienne; Hainault, Isabelle; Bizot-Espiard, Jean-Guy; Caignard, Daniel-Henri; Sergheraert, Christian [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 13, p. 4490 - 4518]
[11]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US2002/165218, 2002, A1
[12]Knight, Zachary A.; Chiang, Gary G.; Alaimo, Peter J.; Kenski, Denise M.; Ho, Caroline B.; Coan, Kristin; Abraham, Robert T.; Shokat, Kevan M. [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 17, p. 4749 - 4759]
[13]Loewe; Urbanietz [Arzneimittel-Forschung/Drug Research, 1974, vol. 24, # 12, p. 1927 - 1933]
[14]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2004/18419, 2004, A2 Location in patent: Page 264-265
[15]Ramachandran, Sreekanth; Hameed P., Shahul; Srivastava, Abhishek; Shanbhag, Gajanan; Morayya, Sapna; Rautela, Nikhil; Awasthy, Disha; Kavanagh, Stefan; Bharath, Sowmya; Reddy, Jitendar; Panduga, Vijender; Prabhakar; Saralaya, Ramanatha; Nanduri, Robert; Raichurkar, Anandkumar; Menasinakai, Sreenivasaiah; Achar, Vijayashree; Jiménez-Díaz, María Belén; Martínez, María Santos; Angulo-Barturen, Iñigo; Ferrer, Santiago; Sanz, Laura María; Gamo, Francisco Javier; Duffy, Sandra; Avery, Vicky M.; Waterson, David; Lee, Marcus C. S.; Coburn-Flynn, Olivia; Fidock, David A.; Iyer, Pravin S.; Narayanan, Shridhar; Hosagrahara, Vinayak; Sambandamurthy, Vasan K. [Journal of Medicinal Chemistry, 2014, vol. 57, # 15, p. 6642 - 6652]
  • 6
  • [ 110-89-4 ]
  • [ 1635-61-6 ]
  • [ 54997-99-8 ]
YieldReaction ConditionsOperation in experiment
87% With potassium carbonate In N,N-dimethyl-formamide for 24h; Heating;
77% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 4h;
60% With potassium carbonate In DMF (N,N-dimethyl-formamide) at 120℃; for 24h; 448.448A Example 448; 3-(3-methoxy-4-nitrophenyl)-7-piperidin-1-yl-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11- one; Example 448A; 2-nitro-5-piperidin-1-ylphenylamine A mixture of 5-chloro-2-nitroaniline (1. 73G, 10 mmol), piperidine (1.09 mL, 11 MMOL), and K2CO3 (1.52g, 11 mmol) in DMF was heated to 120 C for 24 hours. Cooled to room temperature. Partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MGSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 4: 1 hexanes/ethyl acetate to provide 1.33g (60%) of the desired product. MS (ESI) M/E 222 (M+H) +, IH NMR (300MHZ, DMSO-D6) : # 7.79 (d, J=9.83 Hz, 1H), 7.22 (s, 2H), 6.37 (dd, J=9.83, 2.71 Hz, 1H), 6.19 (d, J=2.71 Hz, 1H), 3.34-3. 38 (m, 4H), 1.53-1. 60 (m, 6H).
22% With potassium carbonate In water; N,N-dimethyl-formamide 18 2-Nitro-5-piperidin-1-yl-phenylamine EXAMPLE 18 2-Nitro-5-piperidin-1-yl-phenylamine A mixture of 5-chloro-2-nitrophenylamine (5 g, 29 mmol), piperidine (2.9 mL, 29 mmol), and K2CO3 (4.0 g, 29 mmol) in DMF (20 mL) was stirred at 120° C. for 4 h. The reaction mixture was cooled to room temperature and poured into ice cold water (100 mL). The crude solid product was collected by filtration, air dried, and purified by flash chromatography (silica gel, 4*15 cm, eluted with CHCl3) to yield the product as orange crystals (1.4 g, 22%). See, Aust. J. Chem., 47:247-262 (1994). 1H NMR (90 MHz, CDCl3) δ7.90 (d, J=9.9 Hz, 1H, 6.25-6.00 (m, 3H), 5.86 (d, J=2.6 Hz, 1H), 3.29 (br s, 4H), 1.58 (br s, 6H).

  • 7
  • [ 110-85-0 ]
  • [ 1635-61-6 ]
  • [ 96103-52-5 ]
YieldReaction ConditionsOperation in experiment
100% With caesium carbonate In N,N-dimethyl-formamide at 120℃; for 24h;
93% for 5h; Heating;
84% With potassium carbonate In N,N-dimethyl acetamide at 120℃; for 21h; 1 5- (Piperazin-1'-vl)-2-nitroaniline (13) A mixture of 5-chloro-2-nitroaniline (5. 10 g, 29. 5 mmol), piperazine (12.6 g, 147 mmol) and anhydrous potassium carbonate (4.10 g. 29.7 mmol) in anhydrous N, N- dimethylacetamide (50 ml) was stirred at-120° for 21 h. After cooling to room temperature, the red-brown mixture was poured into crushed ice. The resultant orange suspension was extracted with dichloromethane (x 5). The combined organic extract was re-extracted into aqueous hydrochloric acid (x 2,5%). The combined orange aqueous phase was washed with dichloromethane and collected. Aqueous sodium hydroxide (30%) was added at 0° until pH- 10. A yellow precipitate started to form. The suspension was stirred at 0° for 45 min, and then left to stand at room temperature over the weekend before filtration. The crystalline yellow solid residue was washed with water, then with ether, and dried at the water pump. This was followed by further drying under vacuum in a dessicator for 20 h to give 5-(piperazin-1'-yl)-2-nitroaniline (13) (5.43 g, 84%) m. p. 166-9° (lit. 177- 8°, lit. 170°). 1H nmr (300 MHz, d4-MeOH/dl-TFA): 5 3.33 (m, 4H) H3', H5'; 3.56 (m, 4H) H2', H6' ; 6.27 (d, J2. 7 Hz, 1H) H6; 6.39 (dd, J9. 8,2. 7 Hz, 1H) H4; 7.97 (d, J9. 8 Hz, 1H) H3.
76.16% In butan-1-ol for 40h; Heating;
72.5% With potassium carbonate In acetone at 150℃; for 15h;
70% With potassium carbonate In ethyl acetate; N,N-dimethyl-formamide 20 2-Nitro-5-piperazin-1-yl-phenylamine EXAMPLE 20 2-Nitro-5-piperazin-1-yl-phenylamine A mixture of 5-chloro-2-nitrophenylamine (4.3 g, 25 mmol), piperazine (12.5 g, 145 mmol), and K2CO3 (4.0 g, 29 mmol) in DMF (50 mL) was stirred at 150° C. for 18 h. The reaction mixture was cooled to room temperature, solids were removed by filtration, and the filtrate was concentrated to a red residue. The residue was dissolved in EtOAc (100 mL), washed with water (50 mL), dried with Na2SO4, and concentrated in vacuo to afford the product as a yellow solid (3.9 g, 70%). See, Pharmazie, 39:747 (1984). 1H NMR (90 MHz, d6-DMSO) δ7.89 (d, J=9.9 Hz, 1H), 7.09 (br s, 2H), 6.35-6.20 (m, 2H), 3.33 (t, J=4.6 Hz, 4H), 2.91 (t, J=4.8 Hz, 4H).
With potassium carbonate In N,N-dimethyl-formamide at 130℃; for 8h;
[0156] Compound 3, the N-desmethyl metabolite of Compound 1, was synthesized as shown in the scheme below. 5-Chloro-2-nitroaniline was treated with piperazine to yield 4 which was subsequently protected with a butyloxycarbonyl (Boc) group to yield 5. Reduction of the nitro group followed by condensation with 3-ethoxy-3-iminopropionic acid ethyl ester gave 6. Condensation of 6 with 6-fluoroanthranilonitrile using potassium hexamethyldisilazide as the base yielded 7. Crude 7 was treated with aqueous HCI to yield the desired metabolite as a yellow/brown solid after purification.
With potassium carbonate In N,N-dimethyl-formamide for 16h; Inert atmosphere;
Compound 3, the N-desmethyl metabolite of Compound 1 , was synthesized as shown in the scheme below. 5-Chloro-2-nitroaniline was treated with piperazine to yield 4 which was subsequently protected with a butyloxycarbonyl (Boc) group to yield 5. Reduction of the nitro group followed by condensation with 3-ethoxy-3-iminopropionic acid ethyl ester gave 6. Condensation of 6 with 6-fluoroanthranilonitrile using potassium hexamethyldisilazide as the base yielded 7. Crude 7 was treated with aqueous HCI to yield the desired metabolite as a yellow/brown solid after purification.
Compound 3, the N-desmethyl metabolite of Compound 1, was synthesized as shown in the scheme below. 5-Chloro-2-nitroaniline was treated with piperazine to yield 4 which was subsequently protected with a butyloxycarbonyl (Boc) group to yield 5. Reduction of the nitro group followed by condensation with 3-ethoxy-3-iminopropionic acid ethyl ester gave 6. Condensation of 6 with 6- fluoroanthranilonitrile using potassium hexamethyldisilazide as the base yielded 7. Crude 7 was treated with aqueous HCl to yield the desired metabolite as a yellow/brown solid after purification.
Alkaline conditions;

Reference: [1]Location in patent: experimental part De La Fuente, Tania; Martín-Fontecha, Mar; Sallander, Jessica; Benhamú, Bellinda; Campillo, Mercedes; Medina, Rocío A.; Pellissier, Lucie P.; Claeysen, Sylvie; Dumuis, Aline; Pardo, Leonardo; López-Rodríguez, María L. [Journal of Medicinal Chemistry, 2010, vol. 53, # 3, p. 1357 - 1369]
[2]Kuznetsov, V. A.; Garabadzhiu, A. V.; Ginzburg, O. F. [Journal of Organic Chemistry USSR (English Translation), 1987, vol. 23, p. 576 - 580][Zhurnal Organicheskoi Khimii, 1987, vol. 23, # 3, p. 637 - 642]
[3]Current Patent Assignee: PETER MACCALLUM CANCER CENTER - WO2005/82894, 2005, A1 Location in patent: Page/Page column 43
[4]Sanchez-Alonso; Ravina; Santana; Garcia-Mera; Sanmartin; Baltar [Pharmazie, 1989, vol. 44, # 9, p. 606 - 607]
[5]Abuzar; Sharma [Pharmazie, 1984, vol. 39, # 11, p. 747 - 749]
[6]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US2002/165218, 2002, A1
[7]Minehan, Thomas G.; Gottwald, Konstanze; Dervan, Peter B. [Helvetica Chimica Acta, 2000, vol. 83, # 9, p. 2197 - 2213]
[8]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2006/81445, 2006, A2 Location in patent: Page/Page column 50-51
[9]Ramachandran, Sreekanth; Hameed P., Shahul; Srivastava, Abhishek; Shanbhag, Gajanan; Morayya, Sapna; Rautela, Nikhil; Awasthy, Disha; Kavanagh, Stefan; Bharath, Sowmya; Reddy, Jitendar; Panduga, Vijender; Prabhakar; Saralaya, Ramanatha; Nanduri, Robert; Raichurkar, Anandkumar; Menasinakai, Sreenivasaiah; Achar, Vijayashree; Jiménez-Díaz, María Belén; Martínez, María Santos; Angulo-Barturen, Iñigo; Ferrer, Santiago; Sanz, Laura María; Gamo, Francisco Javier; Duffy, Sandra; Avery, Vicky M.; Waterson, David; Lee, Marcus C. S.; Coburn-Flynn, Olivia; Fidock, David A.; Iyer, Pravin S.; Narayanan, Shridhar; Hosagrahara, Vinayak; Sambandamurthy, Vasan K. [Journal of Medicinal Chemistry, 2014, vol. 57, # 15, p. 6642 - 6652]
[10]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2008/112509, 2008, A1 Location in patent: Page/Page column 40
[11]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2005/82340, 2005, A2 Location in patent: Page/Page column 108
[12]Dobiaš, Juraj; Dvořáková, Hana; Hubálek, Martin; Kozák, Jaroslav; Pomeislová, Alice; Reyes-Gutiérrez, Paul E.; Teplý, Filip; Veverka, Václav; Vrzal, Lukáš [ChemistryOpen, 2020, vol. 9, # 12, p. 1236 - 1250]
  • 8
  • [ 288-32-4 ]
  • [ 1635-61-6 ]
  • [ 131885-65-9 ]
YieldReaction ConditionsOperation in experiment
94% With potassium hydroxide In dimethyl sulfoxide at 80℃; for 3h;
38% With potassium carbonate In dimethyl sulfoxide at 130℃; for 60h; 5 5-(imidazol-1-yl)-2-nitroaniline (16d; see FIG. 5): 100 mg of 5-chloro-2-nitroaniline (10) (0.58 mmol), 80 mg imidazole (1.18 mmol, 2 eq), and 480 mg K2CO3 (3.48 mmol, 6 eq) were mixed in 2 mL DMSO. The reaction mixture was heated at 130° C. for 2.5 days and then diluted with EtOAc/H2O. The EtOAc phase was washed twice with deionized H2O and twice with saturated aqueous NaCl solution. After drying over anhydrous Na2SO4 and filtering, the extract was concentrated by rotary evaporation to give a yellow-orange solid. The crude solid was recrystallized from CHCl3/hexanes to provide pure product as an orange solid. Yield=45 mg (38%).
With sodium carbonate In N,N-dimethyl-formamide at 110℃; for 3h;
With potassium carbonate In <i>N</i>-methyl-acetamide; hydrogenchloride; water 1.A Step A Step A 1-(3-Amino-4-nitrophenyl)imidazole 240 mmol of imidazole, 240 mmol of 2-amino4-chloronitrobenzene and 240 mmol of potassium carbonate in 450 ml of dimethylformamide (DMF) are stirred in a 1 litre round-bottomed flask. The mixture is maintained at 130° C. with stirring for 48 hours. After the DMF has been removed by evaporation, the residue is taken up in water. The precipitate that forms is filtered off and then washed with water. It is then dissolved in 550 ml of 1N hydrochloric acid. After insoluble material has been filtered off, the filtrate is rendered alkaline and the precipitate that forms is filtered off and washed with water. After drying, the expected product is obtained after purification by chromatography on silica gel using a dichloromethane/methanol mixture(95/5). Metting point: 189° C.
0.8 g With potassium hydroxide In dimethyl sulfoxide at 80℃; for 16h; 1 Step-1 :- Preperation of 5-(lH-imidazol- l-yl)-2-nitroaniline Step-1 :- Preperation of 5-(lH-imidazol- l-yl)-2-nitroaniline To a solution of 5-chloro-2-nitroaniline (1.0 g, 5.79 mmol) in DMSO (10 mL) was added imidazole (0.789 g, 11.5 mmol) and KOH (0.660 g, 11.5 mmol). The reaction mass was stirred at 80°C for 16 h. The reaction mixture was cooled to rt, quenched with water and extracted with DCM. The organic layers were dried over anhydrous sodium sulphate, dried and concentrated to afford 0.800 g of title product. 1H NMR (300 MHz, DMSO-d6): δ 8.28 (s, 1H), 8.12-8.09 (d, J = 6.0 Hz, 1H), 7.69 (s, 1H), 7.55 (d, 2H), 7.19 (s, 1H), 7.15 (s, 1H), 6.98-6.95 (d, J = 9.3 Hz, 1H); MS [M+H]+: 205.
892 mg With potassium carbonate In dimethyl sulfoxide at 150℃; 1 Synthesis of 5-(1 H-imidazol-1 -yl)-2-nitroaniline 5-chloro-2-nitro aniline (3.0 g, 17.4 mmol), imidazole (1 .2 g, 17.6 mmol) and potassium carbonate (7.2 g, 52.1 mmol) were mixed in DMSO and heated at 150 °C overnight. The reaction mixture was poured into water (330 ml) and stirred for 1 hour, filtered and the residue washed with water. The resultant crude material was purified on the biotage using dichloromethane/MeOH to give 892 mg. 1 FI NMR (CD30D, 400 MHz) d: 8.26-8.21 (m, 2H), 7.64 (t, J = 1 .4 Hz, 1 H), 7.20-7.19 (m, 1 H), 7.15 (d, J = 2.4 Hz, 1 H), 6.90 (dd, J = 2.4, 9.3 Hz, 1 H), MS (MALDI): m/z = 205 [M+H]+.

  • 9
  • [ 930-62-1 ]
  • [ 1635-61-6 ]
  • [ 131885-68-2 ]
  • 10
  • [ 1635-61-6 ]
  • [ 506-59-2 ]
  • [ 20691-71-8 ]
YieldReaction ConditionsOperation in experiment
96% Stage #1: 5-chloro-2-nitroaniline; N,N-dimethylammonium chloride With triethylamine In ethanol at 130℃; for 20h; Stage #2: With sodium hydroxide In water 2 Compound 2; 5-Chloro-2-nitroaniline (50 g; 0.29 mol) was added to a 5 Lbom"b followed by ethanol (1.1 L) at 0-5 0C. Dimethylamine hydrochloride (130 g; 1.59 mmol) was added in one portion followed by triethylamine (260 ml) and the "bomb quickly sealed. The bomb was heated to 1300C with stirring at 4 bar for 20 hours. The reaction mixture was then allowed to cool to room temperature and the ethanol was removed under vacuum. 2 M sodium hydroxide solution (1 L) was added to the crude residue and this was extracted with ethyl acetate (1 x 1.3 L then 2 x 500 ml). The combined organic layers were washed with brine (150 ml), dried (magnesium sulphate), filtered and evaporated to give the 5-dimethylamino-2-nitroaniline (50.1 g,
70% With sodium acetate In ethanol at 130℃; for 72h;
  • 11
  • [ 1635-61-6 ]
  • [ 108-98-5 ]
  • [ 43156-47-4 ]
YieldReaction ConditionsOperation in experiment
96.4% With ammonia; In isopropyl alcohol; Example 2 In an autoclave, 255 g of 5-chloro-2-nitroaniline (78.3percent by weight) were suspended in 250 ml of isopropanol. The reaction mixture was heated to 60° C. and 95.7 g of ammonia were pumped into the autoclave, resulting in a pressure of 9 bar. At this temperature, 161 g of thiophenol (98percent by weight) were then pumped into the autoclave over the course of 1.5 hours. At the same time, the pressure was maintained at 9 bar by further metered addition of ammonia. After 6 hours, the autoclave was cooled to room temperature and vented. The content of the autoclave was filtered off, the autoclave was rinsed with isopropanol and the liquid used for rinsing was also filtered off. The combined residues were washed with water and dried. This gave 298.6 g of 2-nitro-5-(phenylthio)-aniline in the form of a yellow powder having a content of 91.2percent by weight. This corresponds to a yield of 96.4percent of theory.
95.8% With ammonia; In 2-methyl-propan-1-ol; Example 3 In an autoclave, 200 g of 5-chloro-2-nitroaniline (79.2percent by weight) were suspended in 200 ml of isobutanol. The reaction mixture was heated to 60° C. and 26 g of ammonia were pumped into the autoclave, resulting in a pressure of 4 bar. At this temperature, 126 g of thiophenol (98percent by weight) were then pumped into the autoclave over the course of 1.5 hours. At the same time, the pressure was maintained at 4 bar by further metered addition of ammonia. After 6 hours, the autoclave was cooled to room temperature and vented. The content of the autoclave was filtered off, the autoclave was rinsed with isobutanol and the liquid used for rinsing was also filtered off. The combined residues were washed with water and dried. This gave 240.6 g of 2-nitro-5-(phenylthio)-aniline in the form of a yellow powder having a content of 90.0percent by weight. This corresponds to a yield of 95.8percent of theory.
In N-methyl-acetamide; EXAMPLE I 5 G. of 2-amino-4-chloro-1-nitrobenzene is added to a solution of sodium phenyl mercaptide, prepared under nitrogen from 2.53 g. 57percent sodium hydride and 6.2 ml. thiophenol in 20 ml. dimethylformamide, with a 10 ml. dimethylformamide rinse. The mixture is stirred under nitrogen for three hours at 20°-30°C and then diluted with water. The crude product is washed with water and hexane, then recrystallized from methanol, yielding 2-amino-4-phenylthio-1-nitrobenzene.
With potassium carbonate; In N-methyl-acetamide; water; Thiophenol (44 g.) was added, over a period of 5 minutes and under an atmosphere of dry nitrogen, to a suspension of 5-chloro-2-nitro-aniline (66.5 g.; prepared according to Fuson et al, J. Org. Chem., 12, 799-806, 1947) and anhydrous potassium carbonate (60.6 g.) in dimethylformamide (200 ml.). The reaction mixture was heated under reflux for 8 hours and then cooled. Water (200 ml.) was added dropwise whilst maintaining the temperature at 5°-10° C. The precipitated solid was filtered off, washed well with water and recrystallized from isopropanol, to give 3-amino-4-nitro-diphenyl thioether (83 g.), m.p. 117°-118° C., in the form of a pale brown solid.
In N-methyl-acetamide; water; EXAMPLE XI 2.53 G. 57percent sodium hydride in oil suspension in 20 ml. dimethylformamide is treated with 6.2 ml. thiophenol under nitrogen. 5.0 G. 2-amino-4-chloro-1-nitrobenzene is added and the mixture stirred for three hours. Water is added and the product filtered off and washed with water and hexane. Recrystallization from methanol gives pure 2-amino-4-phenylthio-1-nitrobenzene. 1.8 G.
In N-methyl-acetamide; PREPARATION 3 5 G. of 2-amino-4-chloro-1-nitrobenzene is added to a solution of sodium phenyl mercaptide, prepared under nitrogen from 2.53 g. 57percent sodium hydride and 6.2 ml. thiophenol in 20 ml. dimethylformamide, with a 10 ml. dimethylformamide rinse. The mixture is stirred under nitrogen for 3 hours at 20°-30° C and then diluted with water. The crude product is washed with water and hexane, then recrystallized from methanol, yielding 2-amino-4-phenylthio-1-nitrobenzene.

  • 12
  • [ 1635-61-6 ]
  • [ 108-95-2 ]
  • [ 1552-17-6 ]
YieldReaction ConditionsOperation in experiment
96% With potassium carbonate; In dimethyl sulfoxide; at 80℃; for 2h;Sonication; General procedure: i. A mixture of compound 2a,b (6 mmol), 4a-d (6 mmol), and K2CO3 (9 mmol or 18 mmol for 5c) in DMSO (25 mL) was stirred for 5 h (for 5a), 4 h (for 5b and 5d), 4.35 h (for 5c), and 8 h (for 5f) at 80 C. After cooling, the mixture was poured into water, filtered, dried, and recrystallized from alcohol. ii. A mixture of compound 2a-c (6 mmol), 4a-e (6 mmol), or 1 (3 mmol) and K2CO3 (9 mmol or 18 mmol for 5c) in DMSO (25 mL) was subjected to ultrasound irradiation at 80 C for 1 h (for 3a,b, 5a-d), 6 h (for 5e), and 2 h (for 3c, 5f). After cooling, the mixture was poured into water, filtered, dried, and recrystallized from alcohol.
With potassium carbonate; In chloroform; EXAMPLE 27 STR127 A mixture of 1.09 g of 5-chloro-2-nitroaniline, 10 g of phenol and 2.0 g of anhydrous potassium carbonate was heated at 150 C for 4 days. The reaction mixture was diluted with 1N sodium hydroxide and extracted with ethyl acetate. The ethyl acetate layer was washed with 1N sodium hydroxide, water and brine in turn and dried over anhydrous sodium sulfate. After removal of the solvent, the residue was chromatographed on silica gel using chloroform to give 0.70 g of 2-nitro-5-phenoxyaniline. Mass spectrum (m/z) 230 (M+). NMR (CDCl3) delta: 5.70-6.40 (4H, m), 7.02-7.51 (5H, m), 8.11 (1H, d, J=10 Hz).
With potassium carbonate; In N-methyl-acetamide; water; (d) A mixture of phenol (28.6 g.) 5-chloro-2-nitroaniline (50 g.), anhydrous potassium carbonate (45.4 g.) and dry dimethylformamide (150 ml.) was heated at reflux for 5 hours. The mixture was cooled to room temperature and then treated with water (150 ml.). The solid which precipitated was filtered off and recrystallized from isopropanol to give 3-amino-4-nitrodiphenyl ether (42.9 g.), m.p. 146-148 C.
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 120℃; A phenol (1 equivalent) and 5-CHLORO-2-NITRO ANILINE (1 equivalent) were dissolved in DMF, and solid K2CO3 (2 equivalents) was added in one portion. The reaction mixture was heated at 120 C overnight. The reaction mixture was cooled to room temperature, most of the DMF was distilled off, and water was added to the residue to obtain a precipitate. The solid was dried and purified by chromatography on silicagel (2-10% MEOH/CH2CI2) to afford the desired product. The nitroamine was reduced as in method 1 to give the crude product that was used without further purification.

  • 13
  • [ 326-62-5 ]
  • [ 1635-61-6 ]
  • (3-Amino-4-nitro-phenyl)-(2-fluoro-phenyl)-acetonitrile [ No CAS ]
  • 14
  • [ 1635-61-6 ]
  • [ 658-99-1 ]
  • (3-Amino-4-nitro-phenyl)-(3,4-difluoro-phenyl)-acetonitrile [ No CAS ]
  • 15
  • [ 1635-61-6 ]
  • [ 404-90-0 ]
  • (3-Amino-4-nitro-phenyl)-(3-fluoro-4-methoxy-phenyl)-acetonitrile [ No CAS ]
  • 16
  • [ 7664-93-9 ]
  • [ 7697-37-2 ]
  • [ 108-42-9 ]
  • [ 825-41-2 ]
  • [ 1635-61-6 ]
  • 18
  • [ 13208-31-6 ]
  • [ 7697-37-2 ]
  • [ 64-19-7 ]
  • [ 825-41-2 ]
  • [ 1635-61-6 ]
  • 19
  • [ 3453-33-6 ]
  • [ 1635-61-6 ]
  • [ 288372-38-3 ]
  • [2-(6-methoxy-naphthalen-2-yl)-3<i>H</i>-benzoimidazol-5-yl]-phenyl-methanone [ No CAS ]
  • 20
  • [ 3453-33-6 ]
  • [ 1635-61-6 ]
  • [ 414869-62-8 ]
  • [2-(6-methoxy-naphthalen-2-yl)-3<i>H</i>-benzoimidazol-5-yl]-phenyl-methanone [ No CAS ]
  • 22
  • [ 14400-67-0 ]
  • [ 1635-61-6 ]
  • 2,5-dimethyl-2-(5-chloro-2-nitrophenylazo)-3-oxo-2,3-dihydrofuran [ No CAS ]
  • 23
  • [ 1635-61-6 ]
  • [ 63860-31-1 ]
  • 24
  • [ 1635-61-6 ]
  • [ 124-40-3 ]
  • [ 20691-71-8 ]
YieldReaction ConditionsOperation in experiment
99% With potassium carbonate In N,N-dimethyl-formamide at 150℃; for 12h; N1,N1-Dimethyl-4-nitrobenzene-1,3-diamine (CTDMQ39). To a solution of 5-chloro-2-nitroaniline in dryN,N-dimethylformamide were added K2CO3 and dimethylamine.The mixture was stirred at 150 C for 12 h andquenched with water. After extraction with CH2Cl2, theorganic phase was dried over MgSO4, filtered, andconcentrated under reduced pressure. The crude mixturewas purified by silica gel flash column chromatography(hexane/ethyl acetate, 10/1, v/v). After evaporation of theeluent, compound C-TDMQ39 was obtained as a yellowsolid (99%). 1H NMR (CDCl3): d 8.01 (d, J 9.6 Hz, 1H, H3),6.14 (dd, J 9.6 Hz, 2.6 Hz, 1H, H4), 6.12 (d, J 2.6 Hz, 1H,H6), 3.05 ppm [s, 6H, C5eN(CH3)2].
96% With potassium carbonate In water; N,N-dimethyl-formamide at 150℃; for 12h;
96% In ethanol; water at 90℃; for 120h; sealed thick-walled tube; 28.A To a solution of 5-chloro-2-nitroaniline (4.14 g, 24.0 mmol) in ethanol (62 ml) in a sealed thick-walled tube, was added aqueous 40% dimethylamine solution (22.5 ml, 178 mmol, 7.4 eq) and the mixture heated in a 90 °C oil-bath for 2 days (CAUTION: High pressure). After cooling, additional 40% dimethylamine solution (7.5 ml) was added and heating continued for a further 3 days. The reaction mixture was cooled to room temperature and the contents were tipped onto ice (250 ml). After stirring the suspension was filtered, washed with water (200 ml) and dried under vacuum to give 5- dimethylamino-2-nitroaniline as a bright yellow solid (4.16 g, 96%), mp 138.5-139.8 °C (lit.(8) mp 140 °C).'H nmr (500 MHz, CDC13) δ 3.04, s, 6H, Me2N; 5.76, d (J = 2.7 Hz), 1H, H6; 6.12, dd (J = 2.7, 9.8 Hz), 1H, H4; 7.99, d (J = 9.8 Hz), 1H, H3. 13C nmr (125 MHz, CDCI3) δ 40.4, Me2N; 96.0, C6; 104.5, C4; 124.2, C2; 128.6, C3; 147.4, CI; 155.1, C5.
96% With potassium carbonate In water; N,N-dimethyl-formamide at 150℃; for 12h;
60.9% With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 12h; 22 Example 22: Synthesis of Intermediate 13 The intermediate 5-chloro-2-nitroaniline (12.5g, 72.5mmol)Dissolve 50mL dimethylamine in 50mL dimethylformamide, slowly add potassium carbonate with stirring, and heat and reflux in an oil bath at 90°C for 12 hours. After the reaction is completed, after the reaction is cooled to room temperature, 200 mL of cooled deionized water is added and placed in ultrasound for half an hour, and the solid is collected by suction filtration. After drying, 8.0 g of yellow solid can be obtained with a yield of 60.9%. The structure is as follows

  • 25
  • [ 123-90-0 ]
  • [ 1635-61-6 ]
  • [ 404009-18-3 ]
YieldReaction ConditionsOperation in experiment
91.5% With potassium carbonate; In ISOPROPYLAMIDE; at 135℃; for 24h;Inert atmosphere; A mixture of 5-chloro-2-nitroaniline (5.6 g, 32 mmol), Ihiomorpholine (10.0 g, 97 mmol) and anhydrous potassium carbonate (4.98 g, 36 mmol) in N,N-dimethylacetamide (10 ml) was stirred at 135 C under nitrogen for 1 day. Sample NMR analysis showed complete conversion of the starting material. The resultant mixture was then cooled to room temperature, poured into cold water and stirred vigorously for 3 hours. The resulting brown precipitate was collected by filtration, washed well with water then dried on the filter funnel. The resulting brown solid was washed with diethyl ether, filtered, washed with additional diethyl ether, dried to afford 2-NitGammaO-5-thiomo holin-4-yl- phenylamine (7.0 g, 91.5 %) as a brown powder, and used in the next step without further purification. NMR (400 MHz, CDC13) delta 2.6, m, 4H; 3.75 m, 4H; 5.95, d, (J=2.34 Hz), 1H; 6.1 , s (broad), 2H; 6.18, dd (J=2.3, 7.3 Hz), 1H; 7.98, d (J=9.6 Hz)
  • 26
  • [ 1635-61-6 ]
  • [ 5188-07-8 ]
  • [ 31431-10-4 ]
YieldReaction ConditionsOperation in experiment
87% In N,N-dimethyl-formamide at 65℃; for 20h; Inert atmosphere;
81% In N,N-dimethyl-formamide at 65℃; for 20h; 59.A; 60.A Step A-5-(Methylthio)-2-nitroaniline 5-Chloro-2-nitroaniline (15 g, 87.2 mmol) was dissolved in 250 mL of DMF with stirring. Sodium thiomethoxsde (9.8 g, 140 mmol) was added and the reaction stirred at 65° C. for 20 h. The reaction was cooled to rt and diluted with EtOAc. then washed with water (5×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 12.9 g (81%) of 5-(methylthio)-2-nitroaniline as a red-orange solid. 1H NMR (400 MHz, DMSO-d6) δ 7.85 (d, J=8.97 Hz, 1H), 7.45 (br s, 2 H), 6.78 (d, J=1.83 Hz, 1H), 6.47 (dd, J=1.83 and 9.16 Hz, 1H), 2.47 (s, 3 H).
81% In N,N-dimethyl-formamide at 65℃; for 20h; 59-60.A Example 60: 3-({(1 Rj-142-chloro-3-(4-piperidlnvloxy)pheϖySjethyi}oxv)-5-F6- (methylsulfonyh-I Mbenzimldazoi-i-vn-g-thiophenecarboxamideStep A - 5-(Methylthio)-2-nitiOaniline 5~Chloro-2-nitroanyine (15 g, 87.2 mmo.) was dissolved In 250 ml of DIVIF with stirring. Sodium thtomethoxide (9,8 g, 140 mmol) was added and the reaction stirred at 650C for 20 h. The reaction was cooled Io rt and diluted with EtOAc, then washed with water (5X)1 brine (1x), dried over MgSCU, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 12.9 g (81%) of 5~(methylthio)-2-nitroaniline as a red-orange solid. 1H HMR (400 MHz, DMSO-Cl6) δ 7,85 (d, J- 8.97 Hz1 1 H), 7.45 (br s, 2 H), 6,78 (d, J^ 1.83 Hz, 1 H), 6.47 (dd, J^ 1.83 and 9.10 Hz, 1 H)1 2.47 (s, 3 H).
75% In N,N-dimethyl-formamide at 65℃; for 20h; 6-1.1 Step 1 : 5-(methylthio)-2-nitrobenzenamine A solution of 5-chloro-2-nitroaniline (15.0 g, 86.7 mmol) and sodium thiomethoxide (24.0 g, 346 mmol) in N,N-dimethylformamide (100 mL) stirred for 20 h at 65 °C in an oil bath. The reaction mixture was cooled to room temperature and diluted with 500 mL of ethyl acetate. The resulting mixture was washed with 5x400 mL of water and 500 mL of brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography with silica gel (eluting with ethyl acetate/petroleum ether (1 :3)) to give 5-(methylthio)-2-nitrobenzenamine (12 g, 75%) as a red solid. MS: (ESI, m/z): 185[M+H]+.
In N,N-dimethyl-formamide at 65℃; for 20h; 22.1 5-(Methylsulfanyl)-2-nitroaniline Into a 250 mL round-bottom flask equipped with a magnetic stirbar was added 5- chloro-2-nitroaniline (15.0 g, 87.0 mmol) and DMF (125 mL). The yellow-orange solution was treated with portion wise addition of sodium thiomethoxide (9.75 g, 139.0 mmol) and the resulting mixture was heated to 65 0C for 20 h. The mixture was cooled to room temperature and poured into a 500 mL separatory funnel containing water (250 mL) and extracted with ethyl acetate (3 x 75 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. Purification by column chromatography through silica gel, eluting with 0% EtOAc in hexanes to 50% EtOAc in hexanes as a gradient afforded the title compound as an orange solid.

  • 27
  • [ 27129-86-8 ]
  • [ 1635-61-6 ]
  • [ 934417-60-4 ]
YieldReaction ConditionsOperation in experiment
General procedure: A mixture of anhydrous sodium hydride (5mmol) and 2-nitroaniline (138mg, 1mmol) or 5-chloro-2-nitroaniline (173mg, 1mmol) in DMF (5mL) was stirred for 10min at 0C and then 3,5-dimethylbenzyl bromide (597mg, 3mmol) or 3,5-dimethylbenzensulphonyl chloride (614mg, 3mmol) was added. When the reaction was completed (2-6h) a saturated NaHCO3 aqueous solution was added. The mixture was extracted with dichloromethane (3×10mL) and dried over Na2SO4. After removal of the solvent under reduced pressure, the residue was triturated by treatment with diethyl ether and crystallized from ethanol.
  • 28
  • [ 1635-61-6 ]
  • [ 74-88-4 ]
  • [ 35966-84-8 ]
YieldReaction ConditionsOperation in experiment
100% With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃;
95% Stage #1: 5-chloro-2-nitroaniline With sodium hydride In tetrahydrofuran; paraffin oil at 0℃; for 0.25h; Stage #2: methyl iodide In tetrahydrofuran; paraffin oil at 20℃; for 2h; To a cooled (0°C) solution of 5-chloro-2-nitroaniline (XV, 690mg, 4.0mmol, 1.0 equiv.) in THF (10mL), NaH (60% suspension in paraffin oil, 352mg, 8.8mmol, 2.2 equiv.) was slowly added, and the mixture was allowed to stir for 15min. Then, MeI (374μL, 6.0mmol, 1.5 equiv.) was added dropwise and the mixture stirred at room temperature for 2h. After the reaction was complete, EtOAc (50mL) was added and the organic phases washed with H2O (30mL), brine NaCl (20mL), dried with MgSO4, and evaporated under reduced pressure. The product, 5-chloro-N-methyl-2-nitroaniline (XVII, 707mg, 95% yield) was obtained as a yellow solid. Physical and spectroscopic data were identical to those reported previously [78].
  • 29
  • [ 1635-61-6 ]
  • [ 335349-57-0 ]
YieldReaction ConditionsOperation in experiment
88% With N-iodo-succinimide; acetic acid; In water; at 50℃; for 3.0h;Inert atmosphere; Compound number 103 (i.e., 6-chloro-5-(3-chlorophenyl)-2-trifluoromethylthiobenzimidazole) was prepared as follows. A 50-mL round-bottom flask was purged and maintained with an inert atmosphere of nitrogen. 5-chloro-2-nitroaniline (10 g, 57.95 mmol, 1.00 equiv), acetic acid (100 mL) and NIS (13 g, 57.78 mmol, 1.00 equiv) was placed in the flask. The resulting solution was stirred for 3 h at 50 C. in an oil bath. The resulting solution was poured into 300 mL of H2O. The solid was collected by filtration. The solid was washed with 200 mL of (sat.) sodium bicarbonate and 3×200 mL of H2O. This resulted in 17 g (88%) of 5-chloro-4-iodo-2-nitroaniline as a yellow solid.
85% With N-iodo-succinimide; acetic acid; at 55℃; for 2.0h;Large scale; Compound 1 is2-nitro-5-chloro-aniline(1500 g, 8.7 mol) was added to 15 L of acetic acid,Then add N-iodosuccinimide See 3(1957. (^, 8.711101), heated to 55 (: reaction 211, 11 (: test the end of the reaction).The reaction solution was cooled to 10 C, filtered, the cake was washed with acetic acid, washed with water and saturated sodium bicarbonate solution, and washed with water until neutral.The crude product was dried to give the compound 2S 2-nitro-4-iodo-5-chloroaniline (2200 g, 7.4 mol) in 85%
84% With potassium acetate; Iodine monochloride; acetic acid; at 60℃; for 18.0h; 5-chloro-2-nitroaniline (5.00 g, 29.0 mmol), potassium acetate (5.69 g, 57.9 mmol) and iodine monochloride (9.41 g, 57.9 mmol) were stirred in acetic acid (100 ml) at 60C for 18h. Water was added to the mixture and the resulting suspension was filtered, washed with water and dried at 60C under reduced pressure to give 7.2 g (84 % yield) of the title compound. 1H NMR (400 MHz, DMSO-d6) _ ppm 7.26 (s, 1H) 7.60 (s, 2 H) 8.36 (s, 1H)
With Iodine monochloride; In sodium acetate; acetic acid; Example A1 5-Chloro-4-iodo-2-nitro-phenylamine Prepared from 5-chloro-2-nitroaniline by iodination with iodine monochloride in HOAc/NaOAc according to the general procedure A (80 C.). Obtained as an orange solid. MS (EI) 298 (M+) and 300 [(M+2)+]; mp 202-203 C. (dec.).
With Iodine monochloride; In sodium acetate; acetic acid; Example A1 5-Chloro-4-iodo-2-nitro-phenylamine The title compound was prepared from 5-chloro-2-nitroaniline by iodination with iodine monochloride in HOAc/NaOAc according to the general procedure A (80 C.). Obtained as an orange solid. MS (EI) 298 (M+) and 300 [(M+2)+]; mp 202-203 C. (dec.).
With N-iodo-succinimide; acetic acid; at 50℃; Step A 5-chloro-4-iodo-2-nitroaniline. To a solution of 5-chloro-2-nitroaniline (25 g, 145 mmol) in AcOH (250 mL) was added N-iodosuccinimide (32.6 g 145 mmol). The mixture was stirred overnight at 50 C., cooled down to rt and filtered. The solid residue was washed with AcOH, water, saturated aqueous NaHCO3 and water, a nd then dried to afford the desired product as a brown solid, which was used in the next step without further purification.
With N-iodo-succinimide; In acetic acid; at 55℃; for 16.0h; A mixture of 5-chloro-2-nitroaniline (20.1 g, 116 tnmol) and N-iodosuccinimide (26.2 g, 116 mmol) in 260 niL of acetic acid was heated at 55 C for 16 h and then cooled in an ice-bath. The resulting yellow solid was collected by filtration and rinsed with acetic acid, water, aqueous NaHCO3 and water, and let stand in air for 2 h to provide 5-chloro-4-iodo-2~mtroaniline 1-5 as a yellow solid. 1H NMR (500 MHz, DMSO-d6): delta 7.23 (s, IH)5 8.32 (S5 IH)5 7.57 (s, 2H).
With N-iodo-succinimide; In acetic acid; at 50℃; To a solution of 5-chloro-2-nitroaniline (25 g, 145 mmol) in AcOH (250 mL) was added LambdaModosuccinimide (32.6 g 145 mmol). The mixture was stirred overnight at 500C, cooled to rt and filtered. The solid residue was washed with AcOH, water, saturated aqueous NaHCO3 and water, and then dried to afford the desired product as a brown solid, which was used in the next step without further purification.
With N-chloro-succinimide; In acetic acid; at 50℃; To a solution of 5-chloro-2-nitroaniline (25 g, 145 mmol) in AcOH (250 mL) was added JV-iodosuccinimide (32.6 g 145 mmol). The mixture was stirred overnight at 5O0C, cooled to rt and filtered. The solid residue was washed with AcOH, water, saturated aqueous NaHCO3 and water, and then dried to afford the desired product as a brown solid, which was used in the next step without further purification.
To a solution of 5-chloro-2-nitroaniline (25 g, 145 mmol) in AcOH (250 mL) was added N-iodosuccinimide (32.6 g 145 mmol). The mixture was stirred overnight at 50 C, cooled down to rt and filtered. The solid residue was washed with AcOH, water, saturated aqueous NaHC03 and water, and then dried to afford the desired product as a brown solid, which was used in the next step without further purification.
With sodium acetate; Iodine monochloride; acetic acid; at 90℃; for 3.0h; EXAMPLE 31A; 5-chloro-4-iodo-2-nitroaniline; To a mixture of 5-chloro-2-nitroaniline (8.63 g, 50 mmol) and sodium acetate (4.31 g,52.5 mmol) in acetic acid (45 mL) was added a solution of iodine monochloride (8.52 g, 52.5 mmol) in acetic acid (25 mL) slowly. After the addition, the suspension was stirred at 90C for 3 hours. The mixture was cooled and poured into ice-water. The precipitate was collected by filtration and air-dried to afford the title compound. ]H NMR (300 MHz, dimethylsulfoxide-de) delta ppm 8.36 (s, 1 H) 7.60 (s, 2 H) 7.27 (s, 1 H). MS ESI(-) m/z 296.1 (M-H)".

  • 33
  • [ 1635-61-6 ]
  • [ 43210-67-9 ]
  • 35
  • [ 1635-61-6 ]
  • sodium hypochlorite [ No CAS ]
  • [ 144729-44-2 ]
  • 36
  • [ 1635-61-6 ]
  • [ 18378-20-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: KOH, NaOCl / aq. ethanol 2: (i) NH2OH*HCl, EtOH, H2O, (ii) KOH 3: HNO3, H2SO4 4: ethanol
  • 37
  • [ 1635-61-6 ]
  • [ 124-41-4 ]
  • [ 16133-49-6 ]
YieldReaction ConditionsOperation in experiment
99% In methanol at 80℃; for 4h;
85% In methanol at 20℃; for 28h; Inert atmosphere;
In methanol for 18h; Heating / reflux; 1.1 1.1 Preparation of 5-methoxy-2-nitroaniline 10 g of 5-chloro-2-nitroaniline are dissolved in 100 ml of methanol, and 32.3 g of sodium methoxide are added. The reaction mixture is heated at the boil under reflux for 18 hours. After cooling, the mixture is evaporated to dryness, 500 ml of water are added, and the crude product is isolated by filtration. Drying gives 9.15 g of 5-methoxy-2-nitroaniline.
  • 38
  • [ 64-17-5 ]
  • [ 1635-61-6 ]
  • [ 27076-16-0 ]
YieldReaction ConditionsOperation in experiment
94% With sodium at 80℃; for 48h; 506.506A Example 506; 7-ethoxy-3-(3-methoxy-4-nitrophenyl)-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one; Example 506A; 5-ethoxy-2-nitroaniline A mixture of sodium metal (1.86g, 80.9 mmol) and ethanol (65 mL) was stirred at ambient temperature until all of the sodium metal had been consumed. 5-CHLORO-2-NITROANILINE (4.64g, 26.9 mmol) was added and the mixture was heated at 80 C for 48 hours, cooled to room temperature, quenched with water, concentrated under vacuum, diluted with ethyl acetate, washed with water and brine, dried (MGS04), filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel with 7: 3 hexane/ethyl acetate to provide 4.6g (94%) of the desired product. MS (ESI) m/e 183 (M+H) +, IN NMR (300 MHz, DMSO-d6) 8 7.90 (d, J=9.5 Hz, 1H), 7. 46 (br s, 2H), 6.43 (d, J=2.7 Hz, 1H), 6.23 (dd, J=2.7, 9.5 Hz, 1H), 4.04 (q, J=7.1 Hz, 2H), 1.33 (t, J=7.0 Hz, 3H).
  • 39
  • [ 1635-61-6 ]
  • [ 99512-10-4 ]
YieldReaction ConditionsOperation in experiment
23% With zinc(II) cyanide;tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 120℃; for 96h; A solution of 5-chloro-2-nitro-aniline (6.902g, 40 mmol), Zn(CN)2 (2.818g, 24 mmol), and Pd(PPh3)4 (2.31 lg, 2 mmol) in DMF (40 mL) was heated to 120oC for 4 days. Cooled to room temperature. Partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 4:1 hexanes/ethyl acetate to provide 1.49g (23%) of 3-amino-4-nitro-benzonitrile.
  • 40
  • [ 67-56-1 ]
  • [ 1635-61-6 ]
  • [ 16133-49-6 ]
YieldReaction ConditionsOperation in experiment
69% With sodium at 120℃; for 4h; In sealed tube; 162 To freshly prepared sodium methoxide using sodium (900 mg, 39 mmol) and anhydrous methanol (20 mL) was added 3-chloro-6-nitroaniline (2.55 g, 15 mmol). The reaction mixture was heated in a sealed tube at 120° C. for 4 hours. The solvent was removed under reduced pressure and the crude solid was dissolved in water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined ethyl acetate layer was dried over sodium sulfate. The sodium sulfate was removed by filtration and the solvent was removed. The crude was dried to yield a yellow solid (1.75 g, 69%).
  • 41
  • [ 1635-61-6 ]
  • [ 57260-71-6 ]
  • [ 193902-98-6 ]
YieldReaction ConditionsOperation in experiment
85.7% With potassium carbonate In ISOPROPYLAMIDE at 120℃; for 48h; Inert atmosphere; 37.A.i A mixture of 5 -chloro-2-nitro aniline (5.0 g, 29 mmol), piperazine-1 -carboxylic acid tert-butyl ester (17 g, 9.1 mmol) arid anhydrous potassium carbonate (4.4 g, 32 mmol) in N,A/-dimethylacetamide (20 ml) was stirred at 120 °C under nitrogen for 2 days. Sample NMR analysis showed almost complete conversion of the starting material. The resultant mixture was then cooled to room temperature, poured into cold water (50 mL) and stirred vigorously for 2 hours. The resulting yellow precipitate was collected by filtration, washed well with water then dried on the filter funnel. The resulting yellow brown solid was slurried in diethyl ether, filtered, washed with additional diethylether, dried to afford 4-(3- Amino-4-nitro-pheny l)-piperazine- 1 -carboxylic acid tert-butyl ester (8.0 g, 85.7 %) as a yellow powder, and used in the next step without further purification.1H NMR (400 MHz, CDC13) δ 1.4, s, 9H; 3.3, m, 4H; 3.45, m, 4H; 5.9, d (J=2.35 Hz), 1H; 6.15, s (broad), 2H; 6.22, dd (J=2.54, 7.23 Hz), 1H; 8.0, d (J=9.57 Hz), 1H
80% With potassium carbonate In N,N-dimethyl acetamide at 144℃; for 24h; 57 EXAMPLE 57; Scheme for the synthesis of N4-(5-bromo-2-methylphenyl)-N5-[5-(4- methylpiperazin-l-yl)-lH-benzimidazol-2-yl]-lH-imidazole-4,5-dicarboxamide; Synthesis of ter/-butyl 4-(3-amino-4-nitrophenyl)piperazine-l-carboxylate; [00264] 5-Chloro-2-nitroaniline (8.60 g, 50 mmol, commercially available from Aldrich), 1 -tert-butoxycarbonyl piperazine (14.0 g, 75 mmol, commercially available from Aldrich)), anhydrous potassium carbonate (6.9 g, 50 mmol) and DMA (60 mL) were combined in a thick walled pressure fitted with a Teflon stirrer bar and sealed with a Teflon screw-top stopper. The reaction mixture was heated to 144 0C with stirring for 24 hours. The reaction mixture was allowed to cool to room temperature, filtered and the recovered solid washed with ethyl acetate. The filtrate was partitioned between water and ethyl acetate, and the organic layer was washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude material was purified by silica chromatography eluting with 25% ethyl acetate-hexane which gave 11.8 g of før/-butyl 4-(3-amino-4- nitrophenyl)piperazine-l -carboxylate (80% yield). 1H-NMR (400 MHz, MeOH-^): 7.95 (d, IH), 6.37 (dd, IH), 6.18 (d, IH), 3.53 (s, 4H) 3.35 (s, 4H), 1.43 (s, 9H). MS (EI): 323 (MH+).
73% With potassium carbonate In N,N-dimethyl-formamide at 130℃; for 16h; Tert-butyl 4-(3-amino-4-nitrophenyl) piperazine-1-carboxylate (m10). A mixture of tert-butyl piperazine-1-carboxylate (8.09 g, 43.46 mmol), 5-chloro-2-nitroaniline (5.00 g, 28.97 mmol) and potassium carbonate (8.01 g, 57.95 mmol) were dissolved in 100 mL anhydrous DMF, the reaction mixture was stirred at 130 for 16 h. The solvent was cooled to room temperature, extracted with water and ethyl acetate, the combined organic layer was washed with brine, dried over with anhydrous Na2SO4, and concentrated in vacuo. Purified of the residue via flash column chromatography on silica gel afforded m10 as red solid. Yield: 73%. 1H NMR (400 MHz, MeOD) δ 8.24-7.81 (m, 1H), 6.39 (dd, J = 9.8, 2.7 Hz, 1H), 6.21 (d, J = 2.7 Hz, 1H), 3.63-3.54 (m, 4H), 3.44-3.39 (m, 4H), 1.51 (s, 9H).
73% With potassium carbonate In N,N-dimethyl-formamide at 130℃; for 16h; Tert-butyl 4-(3-amino-4-nitrophenyl) piperazine-1-carboxylate (m10). A mixture of tert-butyl piperazine-1-carboxylate (8.09 g, 43.46 mmol), 5-chloro-2-nitroaniline (5.00 g, 28.97 mmol) and potassium carbonate (8.01 g, 57.95 mmol) were dissolved in 100 mL anhydrous DMF, the reaction mixture was stirred at 130 for 16 h. The solvent was cooled to room temperature, extracted with water and ethyl acetate, the combined organic layer was washed with brine, dried over with anhydrous Na2SO4, and concentrated in vacuo. Purified of the residue via flash column chromatography on silica gel afforded m10 as red solid. Yield: 73%. 1H NMR (400 MHz, MeOD) δ 8.24-7.81 (m, 1H), 6.39 (dd, J = 9.8, 2.7 Hz, 1H), 6.21 (d, J = 2.7 Hz, 1H), 3.63-3.54 (m, 4H), 3.44-3.39 (m, 4H), 1.51 (s, 9H).
57% With potassium carbonate In dimethyl sulfoxide at 100℃; for 72h; A64 tert-butyl 4-(3-amino-4-nitrophenyl)piperazine-l-carboxylate tert-butyl 4-(3-amino-4-nitrophenyl)piperazine-l-carboxylate A mixture of 5-chloro-2-nitroaniline (2.5 g, 14.48 mmol), tert-butyl piperazine-l-carboxylate (3.24 g, 17.38 mmol) and K2CO3 (4.0 g, 28.96 mmol) in DMSO (100 mL) was stirred at 100 °C for 3 days. H20 (150 mL) was then added with stirring, suction filtered, rinsed with H20 and dried to give the title compound as a brown solid (2.6 g, 57%). NMR (400 MHz, CDCh) δ 8.04 (d, J=9.79 Hz, 1 H), 6.27 (dd, J=9.66, 2.64 Hz, 1 H), 6.21 - 6.11 (m, 2 H), 5.95 (d, J=2.51 Hz, 1 H), 3.61 - 3.54 (m, 4 H), 3.40 - 3.34 (m, 4 H), 1.50 (s, 9 H); MS ESI [M+H]+ 323.2, calcd for [Ci5H22N404+H]+ 323.2.
56% With potassium carbonate In N,N-dimethyl acetamide at 140℃; for 18h; Preparation of Tert-butyl 4-(3-amino-4-nitrophenyl) piperazine-1- carboxylate To a solution of 5-chloro-2-nitrobenzenamine (1.5g, 8.6 mmol) in l5mL N, Ndimethyl acetamide, tert-butyl piperazine-1-carboxylate (2.4g, 13.0 mmol) and potassium carbonate (3.6g, 26 mmol) were added and stirred at 140 °C for l8hours. The reaction was cooled to room temperature and filtered. The filtrate was concentrated to an oil under reduced pressure. The oil was diluted with water (200mL) and filtered. The precipitate was washed with ether (5OmL) and dried under high vacuum to yield (1.57 g, 56%) of 1 as yellow solid. ‘H NMR (400MHz, Chloroform-d) 5 8.03 (d, J = 9.6 Hz, 1H), 6.25 (dd, J = 9.6 Hz, J = 2.6 Hz, 1H)), 6.17 (bs, 2H), 5.93 (d, J = 2.6 Hz, 1H), 3.56 (t, J = 5.5 Hz,4H), 3.35 (t, J = 5.5 Hz,4H), 1.48(s, 9H). LC/MS M+1 = 323.2.
46% With potassium carbonate In N,N-dimethyl-formamide at 130℃; for 12h; 1.A (A) Preparation of 4-(3-amino-4-nitrophenyl)piperazine-1-carboxylic acid tert-butyl ester (compound represented by formula (1)): Dissolve 15mmol of 4-Boc piperazine in 20mL of DMF,Add 10 mmol of 2-nitro-5-chloroaniline and 12 mmol of potassium carbonate successively, increase the temperature to 130° C., and stir the reaction for 12 hours.Add appropriate amount of water, extract with ethyl acetate, wash with saturated brine, and dry with anhydrous sodium sulfate.Then it was filtered and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography with the eluent of methanol: dichloromethane=1:60 (v/v) to obtain 1.48 g of a yellow solid (the compound represented by formula (1)) ), the yield was 46%.
With 1,4-diaza-bicyclo[2.2.2]octane In dimethyl sulfoxide at 150℃; for 16h; 1.1 Example 1 6-(4-Methanesulfonyl-piperazin-1-yl)-2-phenoxymethyl-1-(4-trifluoromethoxy-benzyl)-1H-benzoimidazole Step 1 4-(3-Amino-4-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester; A mixture of 2 g (11.6 mmol) 5-chloro-2-nitro-phenylamine, 2.14 g (11.6 mmol) piperazine-1-carboxylic acid tert-butyl ester and 1.3 g (11.6 mmol) 1,4-diazo-bicyclo[2.2.2]octane in 20 ml DMSO was heated to 150° C. for 16 h. The mixture was poured onto 200 ml water and extracted with 250 ml ethyl acetate. The emulsion was filtered through decalite and the aqueous phase was extracted with 2×200 ml. The combined organic phases were washed with 2×100 ml water, dried with MgSO4 and evaporated to dryness. The residue was purified with column chromatography on silica eluting with ethyl acetate/hexane to yield the title compound as a yellow solid. MS(ISP): 321.2 (M-H)-.

  • 42
  • [ 1635-61-6 ]
  • [ 16133-49-6 ]
YieldReaction ConditionsOperation in experiment
99% With sodium methylate In <i>N</i>-methyl-acetamide; methanol R.1 5-Methoxy-2-nitroaniline Reference Example 1 5-Methoxy-2-nitroaniline To a solution of 5-chloro-2-nitroaniline (5.0 g) in dimethylformamide (25 ml) was added 24% sodium methoxide in methanol (11 ml) and the mixture was heated at 80° C. for 4 hours. At the end of this time, the reaction mixture was cooled to room temperature and partitioned between ethyl acetate and water. The extract was washed with 20% aqueous sodium chloride solution and insoluble material was filtered off. The filtrate was concentrated in vacuo to give the desired compound (4.8 g, yield 99%). IR spectrum (KBr, ν cm-1): 3477, 3362, 1626, 1412, 1245, 1108, 830. 1H-NMR spectrum (CDCl3, 400 MHz, δ ppm): 3.82(3H, s), 6.15(1H, d, J=2.7 Hz), 6.21(2H, br.s), 6.28(1H, dd, J=9.5, 2.7 Hz), 8.06(1H, d, J=9.5 Hz).
With sodium chloride; sodium methylate In 1,4-dioxane 5 5-Methoxy-2-nitroaniline Preparation 5 5-Methoxy-2-nitroaniline 70 ml of a 28% w/v methanolic solution of sodium methoxide were added at room temperature to a solution of 25 g of 5-chloro-2-nitroaniline in 500 ml of 1,4-dioxane, and the resulting mixture was heated under reflux for 4 hours, after which the solvent was removed by distillation under reduced pressure. The resulting residue was diluted with water, and the resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane in ratios ranging from 1:4 to 1:2 by volume as the eluent, to give 16.3 g of the title compound, melting at 124°-128° C.
With sodium chloride; sodium methylate In 1,4-dioxane 2.a 2(a) 2(a) 5-Methoxy-2-nitroaniline 70 ml of a 28% w/v methanolic solution of sodium methoxide were added at room temperature to a solution of 25 g. of 5-chloro-2-nitroaniline in 500 ml of 1,4-dioxane, and the resulting mixture was heated under reflux for 4 hours, after which the solvent was removed by distillation under reduced pressure. The resulting residue was diluted with water, and the resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane in ratios ranging from 1:4 to 1:2 by volume as the eluent, to give 16.3 g of the title compound, melting at 124°-128° C.
With sodium chloride; sodium methylate In 1,4-dioxane 5 5-Methoxy-2-nitroaniline PREPARATION 5 5-Methoxy-2-nitroaniline 70 ml of a 28% w/v methanolic solution of sodium methoxide were added at room temperature to a solution of 25 g of 5-chloro-2-nitroaniline in 500 ml of 1,4-dioxane, and the resulting mixture was heated under reflux for 4 hours, after which the solvent was removed by distillation under reduced pressure. The resulting residue was diluted with water, and the resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulphate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane in ratios ranging from 1: 4 to 1: 2 by volume as the eluent, to give 16.3 g of the title compound, melting at 124 - 128°C.

  • 43
  • [ 1635-61-6 ]
  • [ 64051-79-2 ]
  • 5-(3'-hydroxypiperidin-1'-yl)-2-nitroaniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% With potassium carbonate; In N,N-dimethyl-formamide; EXAMPLE 21 1-(3-Amino-4-nitrophenyl)-piperidin-3-ol A mixture of 5-chloro-2-nitrophenylamine (1.3 g, 7.0 mmol), <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (3.0 g, 20 mmol), and K2CO3 (3.0 g, 22 mmol) in DMF (10 mL) was stirred at 120 C. for 18 h. The reaction mixture was cooled to room temperature, poured into water (100 mL) and extracted with EtOAc (3*100 mL). The combined organic extracts were dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography (silica gel, 4*7.5 cm, eluted with 50:50 CHCl3/EtOAc) to yield the product as an orange solid (0.89 g, 54%). 1H NMR (90 MHz, d6-DMSO/CDCl3) delta7.77 (d, J=9.0 Hz, 1H), 6.25-6.00 (m, 2H), 3.82-3.25 (m, 3H), 3.02-2.62 (m, 2H), 1.90-1.12 (m, 4H).
  • 44
  • [ 1635-61-6 ]
  • [ 25369-78-2 ]
  • 6-[[(5-Chloro-1H-benzimidazol-2-yl)thio]-methyl]-2-pyridinamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol 92 6-[[(5-Chloro-1H-benzimidazol-2-yl)thio]-methyl]-2-pyridinamine EXAMPLE 92 6-[[(5-Chloro-1H-benzimidazol-2-yl)thio]-methyl]-2-pyridinamine A solution of 20 g (0.12 mole) of 3-chloro-6-nitroaniline in 350 ml of methanol was hydrogenated over 5% palladium on carbon to yield 24.9 g of the corresponding diamino compound. Reaction of the diamino compound with potassium ethylxanthate using the method described in Example 86.yielded 19 g of 5-chloro-2-mercaptobenzimidazole, as confirmed by elemental analysis. The title compound (1.8 g) was prepared by the method of Example 84 using 3.6 g (19 mMol) of 5-chloro-2-mercaptobenzimidazole instead of 2-mercaptobenzimidazole.
  • 45
  • [ 3372-79-0 ]
  • [ 5446-05-9 ]
  • [ 1635-61-6 ]
  • 2,7-di(o-tolyl)-5,10-dimethyl-5,10-dihydrophenazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With iron(III) chloride; EXAMPLE 3 Synthesis of 2,7-bis(o-tolyl)-5,10-dimethyl-5,10-dihydrophenazine 2,7-bis(o-tolyl)-5,10-dimethyl-5,10-dihydrophenazine was prepared from 2,7-dichlorophenazine. The 2,7-dichlorophenazine was prepared from 2-iodo-5-chloronitrobenzene and 2-nitro-5-chloroaniline using an Ullmann type aryl amination, followed by reduction of the nitro groups and ferric chloride oxidation.
  • 46
  • [ 1635-61-6 ]
  • [ 25784-91-2 ]
  • [ 886435-67-2 ]
YieldReaction ConditionsOperation in experiment
86% With pyridine; In dichloromethane; at 0 - 20℃; for 72.5833h; Compound 5; 5-Chloro-2-nitroaniline (1 g; 5.8 mmol) and pyridine (0.64 ml; 8.1 mmol) were dissolved in dichloromethane (10 ml) and cooled to 00C. This was added dropwise EPO <DP n="111"/>over 5 minutes to a solution of <strong>[25784-91-2]2-chloro-5-nitrobenzoyl chloride</strong> (1.34 g; 6.1 mmol) in dichloromethane (5 ml). The reaction was stirred at room temperature for 72 hours before adding further acid chloride (1.34 g) and pyridine (0.64 ml). After 30 minutes, the solvent was evaporated and the bisacylated residue treated with 1 : 1 concentrated ammonia/acetonitrile (10 ml). AU the solvent was removed after 5 minutes and the residue crystallised from 1 : 1 chloroform / heptane (30 ml) to give 2- chloro-N-(5-chloro-2-nitro-phenyl)-5-nitro-benzamide (1.78g, 86%)
  • 47
  • [ 5308-25-8 ]
  • [ 1635-61-6 ]
  • [ 23470-40-8 ]
YieldReaction ConditionsOperation in experiment
92.9% With potassium carbonate; In N,N-dimethyl-formamide; at 130℃;Inert atmosphere; Compound P42: 5-(Morpholin-4-yl)-2-nitroaniline To the flask 2-amino-3-nitro-6-chloropyridine (1.50 g, 8.47 mmol), potassium carbonate (1.30 g, 9.32 mmol) and morpholine (10.5 ml, 119 mmol) were added. The reaction was carried out under argon flow at 130C overnight. The progress of the reaction was monitored by TLC (system: heptane/ethyl acetate, 1 /1 ). The mixture was cooled to room temperature and poured into the ice-water. A precipitated yellow solid was filtered and dried. 1.789 g of the title product were obtained (yield 94.2%). Compound P46: 5-(4-Ethylpiperazin-1 -yl)-2-nitroaniline; The compound was obtained by the method analogous to that described for Compound P42. Starting from 5-chloro-2-nitroaniline (1.50 g, 8.69 mmol), potassium carbonate (1.32 g, 9.56 mmol) and 1 -ethylpiperazine (1.98 g, 17.3 mmol) w 2 ml of DMF, 2.021 g of the title product in the form of a yellow solid were obtained (yield 92.9%). MS-ESI: (m/z) calculated for C12H19N4O2 [ + H]+: 251.15, found 251.1. 1H NMR (300 MHz, CDC ) delta 7.81 (d, J = 9,6 Hz, 1 H), 6.39 (dd, J = 9,6 Hz;2, 1 Hz 1 H), 6.22 (d, J = 2,1 Hz, 1 H), 3.31 (dd, J = 4,5Hz, 4,8Hz, 4H), 2,44 (dd, J = 4,5Hz, 4,8Hz, 4H) 2,35 (q, J = 7.2 Hz, 2H),1.02 (t, J = 7.2 Hz, 3H) ppm.
38% With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 12h; To a solution of 5-chloro-2-nitroaniline (200 mg,1.16 mmol) in dry DMF (4 mL), K2CO3 (240 mg, 1.74 mmol) and compound47 (172 mg, 1.51 mmol) were added. The reaction mixture was heated to 110C for 12 h. Completion of reaction was observed by TLC (1:4/MeOH:CH2Cl2, Rf 0.70). Thereaction mixture was diluted with EtOAc (30 mL), washed successively with H2O (2×30 mL)and brine (20 mL), then dried over MgSO4. The organic layer was removed under reducedpressure and the residue was purified by flash chromatography (SiO2, 1:19/MeOH:CH2Cl2) toafford compound 52 as a yellow solid (110 g, 38%)
With potassium carbonate; In N,N-dimethyl-formamide; at 130℃; for 2h;microwave; 5-Ch.oro-2-nitroaniline (3g, 17.4mmol), 1-ethylpiperazine (4.42ml, 34.9mmol) and potassium carbonate (2.4g, 17.4mmol) in DMF (8ml) were heated at 130C for 2h in a Smithcreator microwave. The mixture was diluted with water and ethyl acetate. A yellow solid formed, it was filtered off and dried to give 1.3g of the title compound. LC/MS Rt = 1.21 , [MH+] 251.2, 252.2
  • 48
  • [ 1635-61-6 ]
  • [ 25369-78-2 ]
YieldReaction ConditionsOperation in experiment
In methanol 18 5-Chloro-2-[(imidazo[1,2-a]pyridin-8-ylmethyl)thio]-1H-benzimidazole STR27 EXAMPLE 18 5-Chloro-2-[(imidazo[1,2-a]pyridin-8-ylmethyl)thio]-1H-benzimidazole STR27 A solution of 20 g (0.12 mole) of 3-chloro-6-nitroaniline in 350 ml of methanol was hydrogenated over 5% palladium on carbon to yield 24.9 g of the corresponding diamino compound. Reaction of the diamino compound with potassium ethylxanthate using the method described in Example 10 yielded 19 g of 5-chloro-2-mercaptobenzimidazole, as confirmed by elemental analysis.
  • 49
  • [ 1635-61-6 ]
  • [ 43156-48-5 ]
  • [ 598-52-7 ]
  • [ 108-98-5 ]
  • [ 79-22-1 ]
  • 5-phenylmercapto-benzimidazole-2-methyl-carbaminate [ No CAS ]
  • [ 43156-47-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In N-methyl-acetamide; water; potassium carbonate; acetic acid; EXAMPLE 40 5-Phenylmercapto-benzimidazole-2-methyl-carbaminate 20.9 g Of S-methyl-thiourea were reacted as described in Example 1 in 27 ml of water with 13.5 ml of chloroformic acid methyl ester, 45.7 ml of 25percent sodium hydroxide solution, 27 ml of glacial acetic acid, 100 ml of water and 29 g of 3,4-diaminodiphenyl-thioether. After recrystallization from a mixture of glacial acetic acid and methanol, 14 g of 4-phenylmercapto-benzimidazole-2-methyl-carbaminate melting at 233°C were obtained. For preparing the 3,4-diamino-diphenyl-thioether used as starting material, 22 g of thiophenol were heated for 6 hours under reflux in 100 ml of dimethylformamide with 5-chloro-2-nitroaniline in the presence of 30g of anhydrous potassium carbonate. The whole was allowed to cool, 100 ml of water were added and the crude product was filtered off with suction. After recrystallization from isopropanol, 38 g of 3-amino-4-nitro-diphenyl-thioether melting at 112°C were obtained. 38 g Of the 3-amino-4-nitro-diphenyl-thioether so obtained were added to a solution prepared by dissolving 180 g of crystal-water containing stannous chloride in 200 ml of glacial acetic acid and saturation with gaseous hydrochloric acid at room temperature.
  • 50
  • [ 1635-61-6 ]
  • [ 13940-96-0 ]
  • [ 108-95-2 ]
  • [ 1552-17-6 ]
YieldReaction ConditionsOperation in experiment
In N-methyl-acetamide; water; potassium carbonate; For preparing the 3,4-diamino-diphenyl ether used as starting material, 172.5 g of 5-chloro-2-nitro-aniline were heated for 4 hours under reflux in 500 ml of dimethylformamide with 94 g of phenol in the presence of 150 g of anhydrous potassium carbonate. After cooling, the reaction mixture was diluted with 1000 ml of water, the 3-amino-4-nitro-diphenyl ether that had precipitated was filtered off with suction and purified by recrystallization from isopropanol. Yield: 110 g; melting point: 142C. 103 g Of the 3-amino-4-nitro-diphenyl ether so obtained were hydrogenated in 800 ml of dimethylformamide with Raney nickel under a pressure of 100 atmospheres gauge at room temperature, the catalyst was then removed by filtration and the solution was evaporated under reduced pressure. The 3,4-diamino-diphenyl ether that had formed was obtained in the form of a sirupy mass which was dissolved in ethanol and used in the reaction as described above.
  • 53
  • [ 6579-54-0 ]
  • [ 1635-61-6 ]
  • [ 1188891-05-5 ]
  • 54
  • [ 1635-61-6 ]
  • [ 827-33-8 ]
YieldReaction ConditionsOperation in experiment
96.5% With N-Bromosuccinimide; acetic acid; at 30℃; for 1h; Step 1: A mixture of 5-chloro-2-nitroaniline (6.0 g, 34.88 mmol) and NBS (6.06 g, 34.0 mmol) in HOAc (240mL) was stirred at 130 C for 1 h. The reaction mixture was poured into water. The precipitate was collected by filtrationand washed with petroleum ether to give 4-bromo-5-chloro-2-nitroaniline as a light brown solid (8.25 g, 96.5%). 1H NMR(300 MHz, DMSO-d6) delta 8.24 (s, 1H), 7.62 (br s, 2H), 7.29 (s, 1H). LCMS (ESI) m/z 251 (M+H)+.
80% With N-Bromosuccinimide; acetic acid; at 25℃; for 16h; [00669] A mixture of 5-chloro-2-nitrobenzenamine (17g, O. lmol), NBS (17g, O. lmol) and CH3COOH (210 ml) was stirred for 16 h at 25 C. The reaction was quenched with water (100 mL) and extracted with ethyl acetate (1000 mL). The organic layer was washed with water (500 mL x 2), dried (Na2S04), filtered and concentrated in vacuo, the crude product was purified by chromatography (silica, ethyl acetate/petroleum ether =1/1) to afford 4-bromo-5-chloro-2-nitrobenzenamine (20g, 0.08mmol, 80%) as a light yellow solid ESI-MS (EI+, m/z): 251 [M+H]+.
75% With N-Bromosuccinimide; In acetic acid; for 0.75h;Reflux; 6.OO g (34.768 mmol) of 5-chloro-2-nitroaniline and 6.06 g (34.073 mmol) of N-bromosuccinimide were dissolved in 240 ml acetic acid. The mixture was boiled under reflux for 45 min. After cooling, the reaction mixture was added to 1.5 1 water. The resultant precipitate was filtered off and dried under high vacuum. The residue was purified by preparative HPLC (eluent: acetonitrile/water, gradient 10:90 ? 90: 10). We obtained 6.75 g (75% of theor.) of the target compound. LC-MS (method 4): R, = 1.19 min; MS (Elmin): m/z = 249 [M-H]+.1H-NMR (400 MHz, DMSO-D6): delta [ppm] = 7.29 (s, IH), 7.62 (sbr, 2H), 8.24 (s, IH).
63.5% With N-Bromosuccinimide; acetic acid; for 0.5h;Heating; 30 g (0.117 mol) of 5-chloro-2-ntiroaniline (CAS 1635-61-6) was synthesized according to the synthetic method described in the reference WO WO 02-020363,Was dissolved in 200 ml of acetic acid (hereinafter referred to as AcOH, CAS 64-19-7)NBS 30 9g (0.174 mol) was added. The reaction solution was heated and stirred for 30 minutes, and it was confirmed that the reaction was completed. A large amount of water was poured into the reaction mixture to form precipitates, and 6 g (63.5%) of intermediate 1-E was obtained in the same manner as in the extraction of intermediate 1-A .
44% With N-Bromosuccinimide; acetic acid; at 110℃; for 1h; Example 45N2-((6-chloro- 1 H-benzo[d]imidazol-5-yl)methyl)-N4-(5-cyclopropyl- 1 H-pyrazol-3 -yl)- pyrimidine-2,4- diamine (1-94) step 1 : - A mixture of 5-chloro-2-nitrobenzenamine (6.0 g, 34.9 mmol) and NBS (6.06 g, 34.0 mmol) in HOAc (240 mL) was heated at 110 C for 1 h. The solution was cooled to RT and the reaction mixture was poured into an ice-water (800 mL). The resulting solid was filtered, washed with water (50 mL x 3), and dry under vacuum to afford 4.0 g (44%) of 4-bromo-5-chloro-2-nitrobenzenamine (246) as yellow solid: MS (ESI) m/z = 250.9 (M-l).

  • 56
  • [ 1635-61-6 ]
  • [ 609-60-9 ]
  • [ 1221884-18-9 ]
  • 58
  • [ 1635-61-6 ]
  • [ 707-07-3 ]
  • [ 4926-65-2 ]
YieldReaction ConditionsOperation in experiment
87% With indium; acetic acid; In ethyl acetate; for 1.5h;Reflux; Inert atmosphere; General procedure: 2-Nitroaniline derivative (1 mmol) was added to a mixture of indium powder (574 mg, 5.0 mmol for 2-nitroaniline, 918 mg 8.0 mmol for 1,2-dinitroarene), and acetic acid (0.572 mL, 10 mmol) in ethyl acetate (2 mL), followed by the addition of trimethyl orthoester (2.0 mmol) in ethyl acetate (3 mL for 2-nitroaniline; 8 mL for 1,2-dinitroarene). The reaction mixture was stirred at reflux under a nitrogen atmosphere. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (30 mL), filtered through Celite, poured into 10% NaHCO3 (30 mL), and then extracted with ethyl acetate (30 mL×3). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was eluted with ethyl acetate/hexane (v/v=10/90) for 2-phenylbenzimidazole derivatives or methanol/dichloromethane (v/v=1/99) for 2-methylbenzimidazole derivatives through a silica gel column to give the corresponding benzimidazoles. The structures of the benzimidazoles were characterized by 1H NMR, 13C NMR, FTIR, and GC-MS, and were mostly known compounds. HRMS data were reported in addition for unknown compounds.
  • 59
  • [ 103-76-4 ]
  • [ 1635-61-6 ]
  • [ 23470-44-2 ]
YieldReaction ConditionsOperation in experiment
95% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 12h; Inert atmosphere;
95% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 12h; Inert atmosphere; 4.1.1 4.1.1 2-[4-(3-Amino-4-nitro-phenyl)-piperazin-1-yl]-ethanol (6) 5-Chloro-2-nitroaniline (2 g, 11.6 mmol) was taken in dry DMF (5 ml) and 2-piperazin-1-yl-ethanol (3g, 23.08 mmol) and K2CO3 (4.8 g, 34.6 mmol) were added to the solution. This mixture was then heated at 110 °C under N2 atmosphere for 12 h until the disappearance of 5-chloro-2-nitroaniline. The crude compound was suspended in water and the product was extracted with ethyl acetate. The organic layer was washed twice with water, dried over anhydrous Na2SO4 and concentrated. This resulted in a pure product as confirmed by TLC (1% MeOH/CHCl3 on pre-coated silica gel) and was isolated as a bright yellow solid (2.93 g, 95% yield). 1H NMR (300 MHz, CDCl3) δ ppm 2.59-2.65 (m, 6H), 3.4 (t, J = 4.8, 4H), 3.7 (t, J = 4.8, 2H), 5.95 (d, J = 2.7, 1H), 6.1 (bs, 2H, NH2), 6.29 (dd, J = 9.3, J = 2.7, 1H), 8.02 (d, J = 9.3, 1H); HRMS: m/z = 267.1457 [M+H]+, Calcd. = 267.1457 [M+H]+; mp 163 °C.
89% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 24h;
77% With potassium carbonate In ISOPROPYLAMIDE at 120 - 125℃; for 24h; Inert atmosphere; 41.A A mixture of 5-chloro-2-nitroaniline (5.0 g, 29.0 mmol), 2-piperazin- 1 -yl-ethanol(11.3 g, 87.0 mmol) and anhydrous potassium carbonate (4.4 g, 31 mmol) in N,N-dimethylacetamide (10 ml) was stirred at 120-125 °C under nitrogen for 1 day. Sample NMR analysis showed complete conversion of the starting material. The resultant mixture was then cooled to room temperature, poured into cold water (30 ml) and stirred vigorously and cooled at 5°C overnight. The resulting yellow precipitate was collected by filtration, washed well with water then dried on the filter funnel. The resulting yellow brown solid was slurried in diethyl ether (30 mL) , filtered, washed with additional diethyl ether, dried to afford 2-[4-(3-Ammo-4-mtro-phenyl)-piperazin-l-yl]-ethanol (6.0 g, 77 %) as a yellow powder. NMR (400 MHz, CDC13) δ 2.50-2.60, m, 6H; 3.30, m, 4H; 3.60 , m, 2H; 5.9, crude d (J=2.15 Hz), 1H; 6.1 broad s , 2H; 6.25, crude dd (not resolved), 1H, 7.76, d (J=9.77 Hz), 1H
33.3% With potassium carbonate In N,N-dimethyl-formamide for 16h; Inert atmosphere;
In N,N-dimethyl-formamide at 120℃; for 24h;

Reference: [1]Maji, Basudeb; Kumar, Krishan; Kaulage, Mangesh; Muniyappa; Bhattacharya, Santanu [Journal of Medicinal Chemistry, 2014, vol. 57, # 16, p. 6973 - 6988]
[2]Kaulage, Mangesh H.; Maji, Basudeb; Pasadi, Sanjeev; Ali, Asfa; Bhattacharya, Santanu; Muniyappa [European Journal of Medicinal Chemistry, 2018, vol. 148, p. 178 - 194]
[3]Maji, Basudeb; Kumar, Krishan; Muniyappa; Bhattacharya, Santanu [Organic and Biomolecular Chemistry, 2015, vol. 13, # 30, p. 8335 - 8348]
[4]Current Patent Assignee: PETER MACCALLUM CANCER CENTER - WO2011/123890, 2011, A1 Location in patent: Page/Page column 157
[5]Ramachandran, Sreekanth; Hameed P., Shahul; Srivastava, Abhishek; Shanbhag, Gajanan; Morayya, Sapna; Rautela, Nikhil; Awasthy, Disha; Kavanagh, Stefan; Bharath, Sowmya; Reddy, Jitendar; Panduga, Vijender; Prabhakar; Saralaya, Ramanatha; Nanduri, Robert; Raichurkar, Anandkumar; Menasinakai, Sreenivasaiah; Achar, Vijayashree; Jiménez-Díaz, María Belén; Martínez, María Santos; Angulo-Barturen, Iñigo; Ferrer, Santiago; Sanz, Laura María; Gamo, Francisco Javier; Duffy, Sandra; Avery, Vicky M.; Waterson, David; Lee, Marcus C. S.; Coburn-Flynn, Olivia; Fidock, David A.; Iyer, Pravin S.; Narayanan, Shridhar; Hosagrahara, Vinayak; Sambandamurthy, Vasan K. [Journal of Medicinal Chemistry, 2014, vol. 57, # 15, p. 6642 - 6652]
[6]Paul, Ananya; Maji, Basudeb; Misra, Santosh K.; Jain, Akash K.; Muniyappa; Bhattacharya, Santanu [Journal of Medicinal Chemistry, 2012, vol. 55, # 17, p. 7460 - 7471]
  • 60
  • [ 6859-99-0 ]
  • [ 1635-61-6 ]
  • 5-(3'-hydroxypiperidin-1'-yl)-2-nitroaniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With potassium carbonate; In ISOPROPYLAMIDE; at 120 - 130℃; for 21h;Inert atmosphere; A mixture of 5 -chloro-2-nitro aniline (1;73 g, 10 mmol), 3-hydroxypiperidine(2.53 g, 25 mmol) and anhydrous potassium carbonate (1.38 g, 10 mmol) in anhydrous N,N-dimethylacetamide (20 ml) was heated in a 120-130 C oil-bath under nitrogen for 21 h. The reaction mixture was then cooled to room temperature, poured into cold water (100 ml) and stirred vigorously for 45 min to give a friable even suspension. The yellow- brown solid was collected by filtration, washed carefully with water (2 10 ml), then dried over phosphorous pentoxide to give 5-(3'-hyd^oxypiperidm-r-yl)-2-mtroaniline (2.04 g, 86%) as a light ochre powder. nmr(10) (400 MHz, dfi-dmso) delta 1.32-1.49, m, 2H, H4' and/or H5'; 1.72, m, 1H, H4' or H5'; 1.88, m, 1H, H4' or H5'; 2.83, dd (J = 8.8, 12.8 Hz), 1H, H2'; 2.96, m, 1H, H6'; 3.50, m, 1H, H3'; 3.59, m, 1H, H6'; 3.68, dd (J = 4.0, 12.8 Hz), 1H, H2'; 4.90, d (J = 4.4 Hz), 1H, 3'-OH; 6.18, d (J = 2.8 Hz), 1H, H6; 6.33, dd (J = 2.6, 9.8 Hz), 1H, H4; 7.22, br s, 2H, 1-NH2; 7.77, d (J = 10.0 Hz), 1H, H3. 13C nmr (100 MHz, de-dmso) delta 21.7, C5'; 32.4, C4'; 46.0, C6'; 53.3, C2'; 64.4, C3'; 96.2, 104.9, C4, C6; 121.9, C2; 126.8, C3; 148.0, 154.2, CI, C5.
  • 61
  • [ 38256-93-8 ]
  • [ 1635-61-6 ]
  • [ 1339046-77-3 ]
YieldReaction ConditionsOperation in experiment
72% With potassium carbonate; In ISOPROPYLAMIDE; at 115 - 120℃; for 48h;Inert atmosphere; A mixture of 5-chloro-2-nitroaniline (2.2 g, 12.7 mmol), (2-methoxy-ethyl)- methyl-amine (3.0 g, 33.7 mmol) and anhydrous potassium carbonate (1.93 g, 14 mmol) in N,N-dimethylacetamide (5 ml) was stirred at 115-120 C under nitrogen for 2 days. Sample NMR analysis showed complete conversion of the starting material. The resultant mixture was then cooled to room temperature, poured into cold water (20 ml) and stirred vigorously and cooled at 5C overnight. The resulting yellow brown precipitate was collected by filtration, washed well with water then dried on the filter funnel. The resulting yellow brown solid was slurried in diethyl ether (20 mL) , filtered, washed with additional diethyl ether, dried to afford N 1 -(2-methoxy-ethyl)-N 1 -methyl-4-nitro- benzene- 1,3- diamine (2.1 g, 72 %) as a yellow brown powder. NMR (400 MHz, CDC13) delta 3.0, s, 3H; 3.35, s, 3H; 3.9, m, 4H; 5.7, d (J=2.54 Hz), 1H; 6.0-6.3 and 6.22, d + broad s, overlapping, 3 H; 8.0, d (J=9.5 Hz), 1H
  • 62
  • [ 1635-61-6 ]
  • [ 31576-51-9 ]
  • [ 1339046-84-2 ]
YieldReaction ConditionsOperation in experiment
45.8% With potassium carbonate; In ISOPROPYLAMIDE; at 120℃; for 72h;Inert atmosphere; A mixture of 5-chloro-2-mtroaniline (1.6 g, 9.3 mmol), 2-(2-methoxy-ethoxy)- ethylamine (2.0 g, 16.8 mmol) and anhydrous potassium carbonate (1.38 g, 10 mmol) in .YN-dimemylacetarnide (3 ml) was stirred at 120 C under nitrogen for 3 days. Sample NMR analysis showed 80% conversion of the starting material. The resultant mixture was then cooled to room temperature, poured into cold water (30 ml) and extracted with ethyl acetate. The organic extract was washed with brine, dried and evaporated. The resulting orange yellow oil was subjected to a silica gel filtration on a 5 cm x 6cm silica gel plug, eluting first with 50% ethyl acetate / petroleum spirits (40-60C), followed by 100% ethyl acetate. Evaporation yielded an orange-red liquid, 1.1 g (45.8% yields). NMR (400 MHz, CDC13) delta 3.2, q (J=5.28 Hz), 2H; 3.34, s, 3H; 3.5, m, 2H;3.6, m, 2H; 3.65 , t (J=5.1 Hz), 2H; 5.6, d (J=2.54 Hz), 1H; 5.9, dd (J=2.35, 7.03 Hz), 1H, 6.20 broad s , 2H; 7.87, d (J=9.4 Hz), 1H
  • 63
  • [ 4045-24-3 ]
  • [ 1635-61-6 ]
  • [ 1339046-12-6 ]
YieldReaction ConditionsOperation in experiment
75% With potassium carbonate; In ISOPROPYLAMIDE; at 110℃; for 21h;Inert atmosphere; A mixture of 5-chloro-2-nitroaniline (0.375 g, 2.17 mmol), <strong>[4045-24-3]4-methoxypiperidine</strong> (0.50 g, 4.34 mmol, 2.0 eq) and anhydrous potassium carbonate (0.36 g, 2.6 mmol) in anhydrous N,N-dimethylacetamide (5 ml) was heated at 110 C under nitrogen for 21 h. The resultant mixture was cooled to room temperature, poured into water (30 ml) and stirred vigorously for 90 min to give an even suspension. The material was centrifuged, the supernatant removed and the residue treated with water (3 x 15 ml), then acetonitrile (2 x 2 ml) with centrifugation and removal of the supernatant between each treatment. The residue was then dried under vacuum to give 5 -(4 ' -methoxypiperidin- 1 ' -y 1 )-2 -nitroaniline (0.312 g, 57%), as a dull yellow powder, mp 142-144 C.Additional material was obtained by passing the acetonitrile soluble material through a plug of silica gel, eluting with 1:1 ethyl acetate/hexane to give a further 100 mg (total yield 75%). nmr (500 MHz, dfi-dmso) delta 1.44, m, 2H, H37H5'; 1.88, m, 2H, H375'; 3.13, ddd (J = 3.5, 9.5, 13.5 Hz), 2H, H276'; 3.26, s, 3H, 4'-MeO; 3.42, app tt (J = 4.0, 8.0 Hz), 1H, Eta4'; 3.61, m, 2H, H276'; 6.21, d (J = 2.5 Hz), 1H, H6; 6.37, dd (J = 2.5, 9.5 Hz), 1H, H4; 7.21, br, 2H, 1-NH2; 7.78, d ( J = 10.0 Hz), 1H, H3. 13C nmr (125 MHz, de-dmso) delta 30.0, C375'; 44.2, C276'; 55.1, 4'-MeO; 75.1, C4'; 97.3, 105.6, C4, C6; 122.8, C2; 127.5, C3; 148.6, 154.7, CI, C5. MS (ESI +ve) m/z 252 (MH+, 100%). HRMS (ESI +ve) mJz 252.13414, Ci2Hi8N303 requires 252.13427 (Delta = 0.5 ppm).
  • 64
  • [ 4318-37-0 ]
  • [ 1635-61-6 ]
  • [ 1104467-40-4 ]
YieldReaction ConditionsOperation in experiment
69% With potassium carbonate; In ISOPROPYLAMIDE; at 125℃;Inert atmosphere; A mixture of 5 -chloro-2-nitro aniline (1.20 g, 7.0 mmol), 1 -methyl homopiperazine(1.03 g, 9.0 mmol, 1.3 eq) and anhydrous potassium carbonate (0.97 g, 7.0 mmol) in anhydrous N.N-dimethylacetamide (20 ml) was heated at 125 C under nitrogen overnight. The resultant mixture was cooled to room temperature, poured into ice- water (30 ml) and extracted with n-butanol (2 x 50 ml). The extract was then evaporated and the red residue subjected to column chromatography (silica gel) eluting with methanol to give 5-(4'- memyl-l4'-diazepan-r-yl)-2-nitroaniline (1.21 g, 69%).*H nmr(9) (400 MHz, CDC13) delta 2.01, m, 2H, H6'; 2.39, s, 3H, 4'-MeN; 2.57, m, 2H, NCH2; 2.70, m, 2H, NCH2; 3.53, m, 2H, NCH2; 3.60, m, 2H, NCH2; 5.76, d ( J = 2.4 Hz), 1H, H6; 6.13, m, 3H, 1-NH2, H4; 8.00, d (J = 10.0 Hz), 1H, H3.
With potassium carbonate; at 90℃; for 20h; A.5-(4-methyl-l, 4-diazepan-l-yl)-2-nitroaniline A mixture of 5-chloro-2-nitroaniline (8.63 g, 50 mmol), 1-methyl- 1,4-diazepane (6.85 g, 60 mmol) and K2CO3 (8.28 g, 60 mmol) was heat at 90 C for 20 h. After diluting with H20 (500 mL) , it was extracted with EtOAc (60 mL x 3), concentrated and dried to give crude 5-(4-methyl-l,4- diazepan-l-yl)-2-nitroaniline as a dark red oil (12.50 g). NMR indicated a mixture of product and 5-chloro-2-nitroaniline (2: 1). NMR (400 MHz, CD3OD) delta 7.72 (d, J=10.0 Hz, 1H), 6.26 (dd, J=9.8, 2.6 Hz, 1H), 6.02 (d, J=2.4 Hz, 1H), 3.66-3.63 (m, 2H), 3.58 (t, J=6.4 Hz, 2H), 2.77-2.74 (m, 2H), 2.62-2.59 (m, 2H), 2.39 (s, 3H), 2.07-2.00 (m, 2H); MS ESI [M+H]+ 251.3, calcd for [Ci2Hi8N402+H]+ 251.15.
  • 68
  • [ 1635-61-6 ]
  • [ 20035-08-9 ]
  • [ 164801-54-1 ]
  • 69
  • [ 14400-67-0 ]
  • [ 1635-61-6 ]
  • [ 851517-43-6 ]
YieldReaction ConditionsOperation in experiment
General procedure: To a suspension of 2-Nitroanilines 2a?2g (10mmol) in water (5mL) and hydrochloric acid (37percent, 2.5mL), a solution of sodium nitrite (0.74g, 10.75mmol) in water (4mL) at 0°C was added dropwise. The mixture was stirred for 1h, diluted with water (30mL) and made acid with concentrated hydrochloric acid (2mL). In the case of 2b,f the reactions were carried out at room temperature. To this solution, freshly distilled <strong>[14400-67-0]2,5-dimethyl-3-oxo-2,3-dihydrofuran</strong> [36] (1.24g, 11mmol) was added and the mixture was stirred for 1h at room temperature. The crude residue was collected by filtration. After drying, it was purified by column chromatography using a dichloromethane/ethyl acetate mixture in gradient as eluent and recrystallized from ethanol.
  • 70
  • [ 758-96-3 ]
  • [ 1635-61-6 ]
  • [ 1537095-91-2 ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate; In toluene; at 120℃; for 4h; General procedure: A solution of 2-nitro-5-substitutedaniline (1 mmol), difference substituted N,N-dimethylamine(1.5 mmol) and phosphorus oxychloride (2.5 mL) in toluene(10 mL) was refluxed for 4 h at 120 8C. The mixture was cooledand poured onto crushed ice, then made basic with sodiumbicarbonate solution. The organic layer was washed with water,then dried over sodium sulfate and evaporated under vacuo. Thecrude material was purified by chromatography on silica gelcolumn using ethyl acetate and petroleum ether (1:1 by volume)as the eluent. The solvent was removed under reduced pressure toafford the different substituted N,N-dimethyl-N0-(2-nitrophenyl)imidamide intermediates (2). Next, a mixture of 2 (1 mmol) andstannous chloride dihydrate (4 mmol) in ethanol (10 mL) wasstirred at room temperature for 1 h. The solvent was removedunder vacuo and the mixture was dissolved in dichloromethaneand washed with sodium bicarbonate solution. The organic layerwas then dried over sodium sulfate and evaporated in vacuo. Thecrude material was purified by chromatography on silica gelcolumn using ethyl acetate and petroleum ether (1:2 by volume) aseluent. The solvent was removed under reduced pressure to give2,5-disubstitued benzimidazoles 3.
  • 71
  • [ 1635-61-6 ]
  • [ 34569-15-8 ]
  • 72
  • [ 1635-61-6 ]
  • (5-chloro-2-nitrophenyl)hydrazine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: 5-chloro-2-nitroaniline With hydrogenchloride In water at 40℃; for 2h; Stage #2: With sodium nitrite In water at -10℃; for 2h; Stage #3: With hydrogenchloride; tin(ll) chloride In water at -30 - -20℃; 2.3.1 (5-Chloro-2-nitrophenyl)hydrazine hydrochloride (2.2) A solution of 5-chloro-2-nitroaniline (5.0 g, 2.9 mmol) in concentrated HCl (57.2 g, 580 mmol) was heated at 40 °C for 2 h. The reaction mixture was cooled to -10 °C, and then a solution of NaNO2 (2.1 g, 30.5 mmol) in water (20 mL) was added dropwise. After stirring for 2 h, the mixture was cooled to -30 °C and added to a solution of SnCl2 (19.6 g, 87 mmol) in concentrated HCl (30 mL) precooled to -30 °C. The reaction mixture was stirred at -20 °C for 1, and then warmed to room temperature and filtered. The title compound 2.2 was obtained as light yellow solid (7.0 g, 100%); mp: 178-180 °C; 1H NMR (DMSO-d6) δ (ppm): 9.39 (br s, 1H), 8.15 (d, J = 8.8 Hz, 1H), 7.45 (s, 1H), 7.06 (d, J = 8.4 Hz, 1H), 3.83 (br s, 3H); HRMS (ESI): m/z, calcd for C6H7ClN3O2 [M+H+]: 188.0221, found 188.0220.
100% Stage #1: 5-chloro-2-nitroaniline With hydrogenchloride In water at 40℃; for 2h; Stage #2: With sodium nitrite In water at -10℃; for 2h; Stage #3: With hydrogenchloride; tin(ll) chloride In water at -30 - -20℃; for 1h; 1.a 2-nitro-5-chlorophenylhydrazine hydrochloride 2-Nitro-5-chloroaniline (58, 29.0 mmol) Was dissolved in concentrated hydrochloric acid (57.28, 580 mmol) 40 ° C: reaction 2 h. Then cooled to -10 ° C, an aqueous solution of sodium nitrite (2.18, 30.45 mmol) was added dropwise (20 ml) Reaction 2h. Cooled to -30 ° C, Drops to a pre-cooled to-30 uq C of SnCl2 (19.6 g, 87 mmol) In concentrated hydrochloric acid (30 mL) -20 ° C reaction 1h, Rushed to room temperature, filtered and dried to give 7.0 g of pale yellow solid in 100% yield
100% Stage #1: 5-chloro-2-nitroaniline With hydrogenchloride In water at 40℃; for 2h; Stage #2: With sodium nitrite In water at -10℃; for 2h; Stage #3: With hydrogenchloride; tin(ll) chloride In water at -30 - -20℃; for 1h; 8.a a) 2-Nitro-5-chlorophenylhydrazine hydrochloride 2-nitro-5-chloroaniline (5g, 29.0mmol) was dissolved in concentrated hydrochloric acid (57.2g, 580mmol) and reacted at 40 ° C for 2h. Then it was cooled to -10 ° C, and an aqueous solution of sodium nitrite (2.1 g, 30.45 mmol) (20 mL) was added dropwise, and the reaction was carried out for 2 h. Cool to -30 ° C, drop into a concentrated solution of SnCl2 (19.6g, 87mmol) pre-cooled to -30 ° C in concentrated hydrochloric acid (30 mL), react at -20 ° C for 1 h, warm to room temperature, filter, and dry to obtain a pale yellow solid 7.0 g, yield 100%, melting point: 178-180 ° C.
100% Stage #1: 5-chloro-2-nitroaniline With hydrogenchloride at 40℃; for 2h; Stage #2: With sodium nitrite In water at -10℃; for 2h; Stage #3: With hydrogenchloride; tin(IV) chloride In water at -30 - -20℃; for 1h;
99% Stage #1: 5-chloro-2-nitroaniline With hydrogenchloride; sodium nitrite In water at -10℃; for 2h; Stage #2: With hydrogenchloride; tin(ll) chloride In water at -30 - -20℃; for 1h; 4.3. General procedure for preparation of phenylhydrazines (5g, 5n) General procedure: 2-Nitro-aniline (1 eq) was dissolved in concentrated hydrochloric acid (20 eq).Then, it was cooled to -10 °C, and an aqueous solution of sodium nitrite (1.05 eq) wasadded dropwise and stirred for 2 h. Then the reaction solution was cooled to -30 °Cand transferred into a solution of SnCl2 (3 eq) in concentrated hydrochloric acid,which was pre-cooled to -30 °C. Then the reaction solution was warmed to -20 °Cand stirred for another 1 h. The precipitate was filtered and dried to give the targetcompound.

  • 73
  • [ 1635-61-6 ]
  • [ 95-54-5 ]
YieldReaction ConditionsOperation in experiment
97% With palladium 10% on activated carbon; hydrazine hydrate In methanol at 120℃; for 0.25h; Microwave irradiation; General procedure: To amixture of halogenated nitroarene (1 mmol), Pd/C(10%),and MeOH (5 mL) was added NH2NH2·H2O (10 mmol), andthe resulting solution was heated at 120 °C by BiotageInitiator Classic microwave synthesizer for 15 min. Themixture was filtered and condensed in vacuo. The crudematerial was purified by flash column chromatographyusing hexanes and EtOAc.
With palladium on activated charcoal; hydrogen In ethanol; ethyl acetate at 20℃; for 5h;
  • 74
  • [ 1635-61-6 ]
  • [ 5654-83-1 ]
  • C13H18N4O2 [ No CAS ]
  • 75
  • [ 389621-84-5 ]
  • [ 1635-61-6 ]
  • (3'-amino-4'-nitrobiphenyl-4-yl)(morpholin-4-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
87.4% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane;Inert atmosphere; Reflux; Compound P64: 5-{1 -[2-(Morpholin-4- l)ethyl]-1 H- razol-4-yl}-2-nitroaniline; 5-Chloro-2-nitroaniline (0.128 g, 0.744 mmol), pinacol ester of 1 -(2-morpholino- ethyl)-1 H-pyrazole-4-boronic acid (0.343 g, 1 .12 mmol) and tetrakis(triphenyl- phosphine)palladium(O) (0.086 g, 0.074 mmol) were placed in the Schlenk-type flask under argon flow and then the system was degassed. After 20 minutes under argon flow to the flask 10.5 ml of degassed 2-methoxyethyl methyl ether and 0.744 ml of degassed 2M Na2C03 solution were added dropwise. The reaction was carried out under reflux. The progress of the reaction was monitored by TLC analysis (system: heptane/ethyl acetate, 5/4). Ether was evaporated and ethyl acetate added. The mixture was filtered through celite layer. The filtrate was added with water and extracted with ethyl acetate (3 x 50 ml). Combined organic phases were washed with brine and dried over anhydrous Na2S04. A brown oil was obtained after filtration and concentration, and was purified by chromatography on silicagel (system: dichlorometan/methanol, 9/1 ). 0.152 g of a crystallizing oil were obtained (yield 64.3%). Compound P70: (3'-Amino-4'-nitrobiphenyl-4-yl)(morpholin-4-yl)methanone: The compound was obtained by the method analogous to that described for Compound P64. Starting from 5-chloro-2-nitroaniline (0.490 g, 2.84 mmol), 4- (morpholinocarbonyl)phenylboronic acid (1.020 g, 4.26 mmol) and tetrakis- (triphenylphosphine)palladium(O) (0.328 g, 0.284 mmol) in the solution in 40 ml of (2-methoxy)ethylmethyl ether with the addition of 2.8 ml of 2M Na2C03 solution, 0.812 g of the title product in the form of a yellow oil were obtained (yield 87.4%). MS-ESI: (m/z) calculated for Ci7Hi6N304 [M - H]": 326.11 , found 326.1. 1H NMR (500 MHz, DMSO-d6) delta 8.06 (d, J = 9.0 Hz, 1 H), 7.72 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.50 (bs, 2H), 7.33 (d, J = 1.9 Hz, 1 H), 6.96 (dd, J = 9.0, 2.0 Hz, 1 H), 3.77 - 3.34 (m, J = 115.9 Hz, 8H).
  • 76
  • [ 492-73-9 ]
  • [ 1635-61-6 ]
  • [ 17401-70-6 ]
YieldReaction ConditionsOperation in experiment
56% With indium; acetic acid In methanol at 50℃; for 1.83333h; Inert atmosphere; 4.2. General procedure for the indium-mediated reductivecyclization of 2-nitroanilines to prepare quinoxaline General procedure: 4.2. General procedure for the indium-mediated reductivecyclization of 2-nitroanilines to prepare quinoxalines A mixture of the 2-nitroaniline derivative (1.0 mmol), dione (1.0or 2.0 mmol), indium (0.574 g, 5.0 mmol), and acetic acid (0.300 g,5 mmol or 0.600 g,10 mmol) or indium chloride (0.221 g,1 mmol or0.265 g,1.2 mmol) in methanol (5 mL) or toluene (5 mL) was stirredat 50 C, 80 C, or reux under a nitrogen atmosphere. After com-pletion of the reaction, the reaction mixture was diluted with ethylacetate (30 mL), ltered through Celite, and the ltrate was pouredinto 10% NaHCO3 (30 mL) and extracted with ethyl acetate(30 mL3). The combined organic extracts were dried over MgSO4,ltered, and concentrated. The residue was eluted with ethyl ace-tate/hexane (v/v10/90) through a silica gel column to give thecorresponding pure quinoxaline. Quinoxaline structures werecharacterized by 1H NMR, 13C NMR, FTIR, and GCeMS, and weremostly known compounds. For unknown compounds, elementalanalysis data were additionally obtained. 4.2.1. 2,3-Dimethylquinoxaline (5).19,31aef Yield 87%. Yellow solid,mp 109e110 C (lit.31f mp 105 C). TLC (10% ethyl acetate/hexane) Rf0.30; 1H NMR (400 MHz, CDCl3) d 7.91 (dd, 2H, J6.3, 3.5 Hz), 7.59(dd, 1H, J6.3, 3.5 Hz), 2.66 (s, 6H); 13C NMR (100 MHz, CDCl3)d 153.4, 141.0, 128.7, 128.2, 23.1; IR (KBr) 3109, 3078, 3030, 2995,2953, 2914, 1490, 1398, 1164 cm1;GCeMS m/z (rel intensity) 158(M, 99), 117 (100), 76 (28), 50 (12).
  • 78
  • [ 1635-61-6 ]
  • [ 17070-58-5 ]
  • benzofuran-2-sulfonic acid (5-chloro-2-nitrophenyl)amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: 5-chloro-2-nitroaniline With sodium hydride In N,N-dimethyl-formamide; mineral oil at -10℃; for 0.166667h; Inert atmosphere; Stage #2: benzofuran-2-sulfonyl chloride In N,N-dimethyl-formamide; mineral oil at -10 - 0℃; for 0.5h; Inert atmosphere; Intermediate 4 Benzofuran-2-sulfonic acid (5-chloro-2-nitro-phenyl)-amide To a -10°C cold yellow solution of 5-chloro-2-nitroaniline (8.00 g, 46.36 mmol) in dry DMF (130 ml) was added sodium hydride 60% (9.27 g, 231.79 mmol) under Ar. The resulting red suspension was stirred at -10°C for 10 minutes. A solution of 1-benzofuran-2-sulfonyl chloride (12.05 g, 55.63 mmol) in dry DMF (50 ml) was added dropwise with a dropping funnel at -10°C (10 minutes of addition, exothermic reaction, maximum temperature of addition was O°C, 5 ml of DMF to rinse the funnel). The resulting orange suspension was stirred at -10°C for 30 minutes (color changed to brown). The reaction mixture was quenched with half saturated NaHCO3 solution (400 ml) and the product was extracted five times with EtOAc (1 x 650 ml and 4 x 300 ml). The combined organic layers were dried over Na2SO4, filtered and the filtrate evaporated to dryness. The crude product was combined with the crude product of an analogously performed 8 g scale attempt to give 61.82 g of an orange oil which was purified by MPLC (crude was dissolved in CH2Cl2/MeOH, preabsorption on silica gel, column D, program 3, 5 runs) to afford Intermediate 4 (28.91 g, 88% yield based on combined starting material) as yellow solid. C14H9ClN2O5S (352.75). HPLC-MS (basic mobile phase, ESl-): tR = 1.31 min, 350.7 [M-H]-. 1H-NMR (DMSO-d6): 7.70 (ddd, J = 0.6, 1.3, 7.8, 1 H); 7.60 (dd, J = 0.8, 8.3, 1 H); 7.52-7.47 (m, 2H); 7.39 (m, 1 H); 7.28 (m, 1 H); 7.18 (s, 1 H); 6.75 (d, J = 8.3, 1H).
  • 79
  • [ 1478-61-1 ]
  • [ 1635-61-6 ]
  • 2,2-bis[4-(3-amino-4-nitrophenoxy)phenyl]hexafluoropropane [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With potassium carbonate; In dimethyl sulfoxide; at 80℃; for 2h;Sonication; Reaction mixture containing 0.028 mol of K2CO3, 0.028 mol of compound 1 and 0.014 mol of compound 2 in 40 mL of DMSO was exposed to ultrasound radiation in a bath (manufactured by the Elma Schmidbauer GmbH, Germany) at 80C for 120 min. After cooling, the mixture was poured into water, filtered, and the precipitate was dried, and crystallized from isopropanol. Yield 94%, mp 182-184C. HRMS: m/z calculated for C27H18F6N4O6: 609.1210 [M+H]+. Found:609.1201. 1H NMR (DMSO-d6, delta, ppm, J, Hz): 6.28(dd, 2H, H6'',6'', J =1.3, 8.2), 6.37 (d, 2H, H2'',2'',J=1.5), 7.23 (d, 4H, H3',3'5',5', J =8.5), 7.46 (d, 4H,H2',2',6',6', J =8.4), 7.50 (s, 4H, 2NH2), 8.10 (d, 2H,H5'',5'', J =8.8).For C27H18F6N2O6 anal. calcd. (%): C, 53.21; H,2.96; N, 9.20. Found (%): C, 53.30; H, 2.93; N, 9.24.
94% With potassium carbonate; In dimethyl sulfoxide; at 80℃; for 2h;Sonication; General procedure: Reaction mixture of K2CO3 (0.034 mol), compound 1 (0.028 mol), and compound 2 (0.014 mol) in DMSO (40 mL) was sonicated at 80 C for 5 min to yield compound 3d, for 100 min to yield 3a, for 120 min to yield 3c, and for 130 min to yield 3b. After cooling down the reaction mixture was poured into water, precipitate was filtered and dried.
92% With potassium carbonate; In dimethyl sulfoxide; at 80℃; for 1h;Sonication; General procedure: i. A mixture of compound 2a,b (6 mmol), 4a-d (6 mmol), and K2CO3 (9 mmol or 18 mmol for 5c) in DMSO (25 mL) was stirred for 5 h (for 5a), 4 h (for 5b and 5d), 4.35 h (for 5c), and 8 h (for 5f) at 80 C. After cooling, the mixture was poured into water, filtered, dried, and recrystallized from alcohol. ii. A mixture of compound 2a-c (6 mmol), 4a-e (6 mmol), or 1 (3 mmol) and K2CO3 (9 mmol or 18 mmol for 5c) in DMSO (25 mL) was subjected to ultrasound irradiation at 80 C for 1 h (for 3a,b, 5a-d), 6 h (for 5e), and 2 h (for 3c, 5f). After cooling, the mixture was poured into water, filtered, dried, and recrystallized from alcohol.
  • 80
  • [ 21867-64-1 ]
  • [ 1635-61-6 ]
  • C13H20N4O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 24h; To a solution of 5-chloro-2-nitroaniline (230mg, 1.33 mmol) in dry DMF (6 mL), K2CO3 (276 mg, 2.00 mmol) andcompound 48 (256 mg, 1.52 mmol) were added. The reaction mixture washeated to 110 C for 24 h. Completion of reaction was observed by TLC (1:1/EtOAc:Hexanes, Rf0.25). The reaction mixture was diluted with EtOAc (30 mL), washed successively with H2O(2×50 mL) and brine (20 mL), and then dried over MgSO4. The organic layer was removedunder reduced pressure and the residue was purified by flash chromatography (SiO2,1:9/MeOH:CH2Cl2) to afford compound 53 as a yellow solid (195 mg, 56%)
  • 81
  • [ 1635-61-6 ]
  • [ 107-02-8 ]
  • [ 6942-98-9 ]
YieldReaction ConditionsOperation in experiment
56% With hydrogenchloride; phosphoric acid; at 80 - 90℃; for 4.0h; first, after adding phosphoric acid 5.03g and hydrochloric acid 55mL to 100mL Erlenmeyer flask to dissolve the 5-chloro-2-nitroaniline (5.02g, 29.1mmol) and Stirring,. Acrolein at 80 degree (5.0mL, 74.8mmol) was added dropwise slowly over a period of 30 minutes, stirred for 3.5 hours at 90 degree .After cooling to room temperature, the reaction mixture was poured into ice water 100 g, was removed by suction filtration precipitate formed.The filtrate ammonia water was added to, was made alkaline (pH 13), the precipitated solid was suction filtered and dried in vacuom was 3.4 g in yield and 56% in yield,
  • 82
  • [ 1635-61-6 ]
  • [ 17636-10-1 ]
  • C9H12N2O5S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 110 - 120℃; for 3h; 50.0 parts of 5-chloro-2-nitroaniline was dissolved in 400 parts of N-methyl-2-pyrrolidone,78.4 parts of <strong>[17636-10-1]sodium 3-mercaptopropanesulfonate</strong> and 48.4 parts of potassium carbonate were added thereto.After the addition, the mixture was heated to 110 to 120 C. and reacted at the same temperature for 3 hours.After cooling to 60 C., the reaction solution was added to 6000 parts of 2-propanol, and after cooling to room temperature, the obtained solid was collected by filtration,468.4 parts of a wet cake containing a compound represented by the following formula (14) was obtained.
  • 83
  • [ 1635-61-6 ]
  • [ 24974-73-0 ]
  • N-(5-chloro-2-nitrophenyl)-1-(3-chlorophenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: 5-chloro-2-nitroaniline With sodium hydride In N,N-dimethyl-formamide for 0.0166667h; Stage #2: (3-chlorophenyl)methanesulfonyl chloride In N,N-dimethyl-formamide 2 4.3.3. N-(5-Chloro-2-nitrophenyl)-1-(3-chlorophenyl)methanesulfonamide (4c) General procedure: 5-Chloro-2-nitroaniline (173 mg, 1 mmol) was dissolved in DMF (3 mL) and dry sodium hydride (120 mg, 5 mmol) was added.The obtained mixture was stirred for 1 min and the suitable substitutedbenzenesulfonyl chloride 1 (a-g) or phenylethanesulfonylchloride 3 (a-g) (1,5 mmol) was added in several portions. The reaction was quenched after 2-6 h through the addition of a saturated NaHCO3 aqueous solution (5 mL). The mixture was extractedwith EtOAc (3 10 mL) and dried over Na2SO4. After removal ofthe solvent under reduced pressure, the residue was purified byflash chromatography using cyclohexane/AcOEt (80:20) as eluentand crystallized from Et2O.
  • 84
  • [ 1635-61-6 ]
  • [ 53531-68-3 ]
  • N-(5-chloro-2-nitrophenyl)-1-(3-methylphenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% Stage #1: 5-chloro-2-nitroaniline With sodium hydride In N,N-dimethyl-formamide for 0.0166667h; Stage #2: (3-methylphenyl)methanesulfonyl chloride In N,N-dimethyl-formamide 5 4.3.6. N-(5-Chloro-2-nitrophenyl)-1-(3-methylphenyl)methanesulfonamide (4f) General procedure: 5-Chloro-2-nitroaniline (173 mg, 1 mmol) was dissolved in DMF (3 mL) and dry sodium hydride (120 mg, 5 mmol) was added.The obtained mixture was stirred for 1 min and the suitable substitutedbenzenesulfonyl chloride 1 (a-g) or phenylethanesulfonylchloride 3 (a-g) (1,5 mmol) was added in several portions. The reaction was quenched after 2-6 h through the addition of a saturated NaHCO3 aqueous solution (5 mL). The mixture was extractedwith EtOAc (3 10 mL) and dried over Na2SO4. After removal ofthe solvent under reduced pressure, the residue was purified byflash chromatography using cyclohexane/AcOEt (80:20) as eluentand crystallized from Et2O.
  • 85
  • [ 1635-61-6 ]
  • [ 51419-59-1 ]
  • N-(5-chloro-2-nitrophenyl)-1-(4-methylphenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% General procedure: 5-Chloro-2-nitroaniline (173 mg, 1 mmol) was dissolved in DMF (3 mL) and dry sodium hydride (120 mg, 5 mmol) was added.The obtained mixture was stirred for 1 min and the suitable substitutedbenzenesulfonyl chloride 1 (a?g) or phenylethanesulfonylchloride 3 (a?g) (1,5 mmol) was added in several portions. The reaction was quenched after 2?6 h through the addition of a saturated NaHCO3 aqueous solution (5 mL). The mixture was extractedwith EtOAc (3 10 mL) and dried over Na2SO4. After removal ofthe solvent under reduced pressure, the residue was purified byflash chromatography using cyclohexane/AcOEt (80:20) as eluentand crystallized from Et2O.
  • 86
  • [ 1635-61-6 ]
  • [ 4025-71-2 ]
  • N-(5-chloro-2-nitrophenyl)-2-phenylethanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% General procedure: 5-Chloro-2-nitroaniline (173 mg, 1 mmol) was dissolved in DMF (3 mL) and dry sodium hydride (120 mg, 5 mmol) was added.The obtained mixture was stirred for 1 min and the suitable substitutedbenzenesulfonyl chloride 1 (a-g) or phenylethanesulfonylchloride 3 (a-g) (1,5 mmol) was added in several portions. The reaction was quenched after 2-6 h through the addition of a saturated NaHCO3 aqueous solution (5 mL). The mixture was extractedwith EtOAc (3 10 mL) and dried over Na2SO4. After removal ofthe solvent under reduced pressure, the residue was purified byflash chromatography using cyclohexane/AcOEt (80:20) as eluentand crystallized from Et2O.
  • 87
  • [ 1635-61-6 ]
  • [ 55215-55-9 ]
  • 88
  • [ 1635-61-6 ]
  • [ 1219737-12-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: acetic acid; N-iodo-succinimide / 50 °C 2: iron; ammonium chloride / ethanol; water / 50 °C / Inert atmosphere 3: potassium hydroxide / ethanol / 3 h / Reflux 4: potassium carbonate / acetone / 1 h / 0 - 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 20 °C 6: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / 1,4-dioxane; water / 0.17 h / 120 °C / Microwave irradiation 7: neat (no solvent) / 3 h / 130 °C / Inert atmosphere; Sealed tube 8: sodium hydroxide / water; methanol / 1 h / 70 °C
Multi-step reaction with 8 steps 1: N-iodo-succinimide; acetic acid / 50 °C 2: ammonium chloride; iron / ethanol; water / 50 °C / Inert atmosphere 3: potassium hydroxide / ethanol; water / 3 h / Reflux 4: potassium carbonate / acetone / 0 - 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 20 °C 6: potassium phosphate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 5 h / 100 °C 7: 3 h / 130 °C / Inert atmosphere; Sealed tube 8: sodium hydroxide / methanol; water / 1 h / 70 °C
  • 89
  • [ 27550-90-9 ]
  • [ 1635-61-6 ]
  • 5-(2-methylmorpholino)-2-nitroaniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With triethylamine; In 1-methyl-pyrrolidin-2-one; at 100℃; for 1h;Microwave irradiation; 5-Chloro-2-nitroaniline (200 mg, 1.159 mmol) was added to a solution of <strong>[27550-90-9]2-methylmorpholine</strong> (176 mg, 1.738 mmol) in NMP (5 mL) in the presence of triethylamine (0.404 mL, 2.90 mmol) and then the reaction mixture was heated via microwave irradiation to 100 C for 1 hour. Following cooling, the solvent was removed by vacuum and the resulting crude material was purified by flash column chromatography (5% CH3OH/CH2Cl2) afforded the title compound as a solid in 70 % yield. 1H NMR: (400 MHz, DMSO-d6): delta 7.79 (d, 1H, J = 9.6 Hz), 7.25 (bs, 2H), 6.39 (dd, 1H, J = 2.8 and 9.6 Hz), 6.20 (d, 1H, J = 2.8 Hz), 3.88 (dd, 1H, J = 2.8 and 12.0 Hz), 3.69 (d, 1H, J = 12.8 Hz), 3.56 (m, 2H), 2.82 (m, 1H), 2.15 (t, 1H, J = 7.6 Hz), 1.88 (m, 1H), 1.12 (d, 3H, J = 6.0 Hz).
  • 90
  • [ 229009-40-9 ]
  • [ 1635-61-6 ]
  • 4’-(4-methylpiperazin-1-yl)-4-nitro-[1,1‘-biphenyl]-3-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 3h;Inert atmosphere; Microwave irradiation; A solution of 5-chloro-2-nitroaniline (580 pmoles), <strong>[229009-40-9](4-(4-methylpiperazin-1-yl)phenyl)boronic acid</strong> (696 pinoles), and potassium carbonate (2 mmoles) was mixed by stirring in dimethylformamide (DMF, 2 mL) under an Argon atmosphere in a 5 mL Biotage microwave vial. After 5 min of mixing, Pd(PPh3)4 (tetrakis(triphenylphosphine)palladium(O), 29 pmoles) was added to the reaction mixture. The vial was capped, placed in the Biotage Initiator-*- SP wave microwave-reactor, and was heated at 100 C for 3 h. The solvent was then removed by rotatory evaporation under reduced pressure. The desired product was purified by column chromatography using a gradient of 0 - 10% methanol in dichloromethane (DCM) (Yield: 145 mg, 80%). MS-ESI (+) HRMS: Calculated (C17H20N4O2) 313.1665 (M + H+); observed: 313.1658 (M + H+). 1H NMR: (CDCI3, 400 MHz) delta 2.30 (3H, s), 2.52 (4H, t, J=5 Hz), 3.23 (4H, t, J=5), 6.85 (1 H, d, J=8 Hz), 6.86 (1 H, s), 6.91 (2H, d, J=8 Hz), 7.44 (2H, d, J=8 Hz), 8.07 (1 H, d, J=9 Hz). 3C NMR: (CDCI3, 100 MHz) delta 46.17, 48.29, 54.93, 114.99, 1 15.56, 1 15.80, 126.82, 127.99, 128.98, 130.81 , 145.04, 148.17, 151.66.
  • 91
  • [ 1478-61-1 ]
  • [ 1635-61-6 ]
  • 2,2-bis[4-(3,4-diaminophenoxy)phenyl]hexafluoropropane [ No CAS ]
  • 92
  • [ 1635-61-6 ]
  • [ 611-07-4 ]
YieldReaction ConditionsOperation in experiment
80.9% With potassium hydroxide; In water; at 150℃; for 4h;Inert atmosphere; Sealed tube; The raw material 2-nitro-5-chloroaniline 0.5 mol, potassium hydroxide 0.6 mol, deionized water 150 ml, and polyethylene glycol (PEG 400) 10 g were mixed and added to the reaction vessel.The reaction vessel was sealed by replacing the air several times with nitrogen, and the temperature was raised to 150 C for 4 h. After completion of the reaction, the reaction vessel was cooled to room temperature and then opened, and the reaction liquid was adjusted to pH = 2 with 20% sulfuric acid to precipitate crude 2-nitro-5-chlorophenol, which was filtered.The filter cake was washed with deionized water three times (each time the amount of deionized water is washed with 30ml), theDrying (drying to constant weight at 80 C) gave 70.2 g of 2-nitro-5-chlorophenol (fine), the yield was 80.9%, and the purity was 99%
  • 93
  • [ 1635-61-6 ]
  • [ 513-85-9 ]
  • [ 17911-93-2 ]
YieldReaction ConditionsOperation in experiment
98% With sodium hydroxide In toluene at 120℃; for 3h; Inert atmosphere; Sealed tube; Green chemistry;
82% With cesiumhydroxide monohydrate In toluene at 150℃; for 28h; Inert atmosphere; Sealed tube; 2.4 Direct synthesis of quinoxaline from nitroamine General procedure: In an oven dried 9mL screw cap tube a magnetic stir-bar, nitroamine (0.5mmol), vicinal diol (2.5mmol), CsOH.H2O (0.125mmol), Co-phen/C-800 (1.5mol%) and toluene (2.5mL) were added under argon atmosphere. Then, the tube was sealed and placed in a preheated oil bath at 150°C for 24h. After completion of the reaction, the tube was allowed to cool at room temperature. Next, the solvent was evaporated under reduced pressure. Finally, the quinoxaline was purified by silica gel column chromatography using ethyl acetate/hexane as eluent.
77% With trimethylamine-N-oxide; tricarbonyl(η4-1,3-bis(trimethylsilyl)-4,5,6,7-tetrahydro-2H-inden-2-one)iron In toluene at 150℃; for 24h; Green chemistry;
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 1635-61-6 ]

Aryls

Chemical Structure| 6641-64-1

[ 6641-64-1 ]

4,5-Dichloro-2-nitroaniline

Similarity: 0.75

Chemical Structure| 15950-17-1

[ 15950-17-1 ]

4-Chloro-N-methyl-2-nitroaniline

Similarity: 0.71

Chemical Structure| 5344-44-5

[ 5344-44-5 ]

3-Chloro-5-nitroaniline

Similarity: 0.70

Chemical Structure| 5348-42-5

[ 5348-42-5 ]

4,5-Dichlorobenzene-1,2-diamine

Similarity: 0.70

Chemical Structure| 25781-92-4

[ 25781-92-4 ]

5-Chloro-2-nitro-N-phenylaniline

Similarity: 0.69

Chlorides

Chemical Structure| 6641-64-1

[ 6641-64-1 ]

4,5-Dichloro-2-nitroaniline

Similarity: 0.75

Chemical Structure| 15950-17-1

[ 15950-17-1 ]

4-Chloro-N-methyl-2-nitroaniline

Similarity: 0.71

Chemical Structure| 5344-44-5

[ 5344-44-5 ]

3-Chloro-5-nitroaniline

Similarity: 0.70

Chemical Structure| 5348-42-5

[ 5348-42-5 ]

4,5-Dichlorobenzene-1,2-diamine

Similarity: 0.70

Chemical Structure| 25781-92-4

[ 25781-92-4 ]

5-Chloro-2-nitro-N-phenylaniline

Similarity: 0.69

Amines

Chemical Structure| 6641-64-1

[ 6641-64-1 ]

4,5-Dichloro-2-nitroaniline

Similarity: 0.75

Chemical Structure| 15950-17-1

[ 15950-17-1 ]

4-Chloro-N-methyl-2-nitroaniline

Similarity: 0.71

Chemical Structure| 5344-44-5

[ 5344-44-5 ]

3-Chloro-5-nitroaniline

Similarity: 0.70

Chemical Structure| 5348-42-5

[ 5348-42-5 ]

4,5-Dichlorobenzene-1,2-diamine

Similarity: 0.70

Chemical Structure| 25781-92-4

[ 25781-92-4 ]

5-Chloro-2-nitro-N-phenylaniline

Similarity: 0.69

Nitroes

Chemical Structure| 6641-64-1

[ 6641-64-1 ]

4,5-Dichloro-2-nitroaniline

Similarity: 0.75

Chemical Structure| 15950-17-1

[ 15950-17-1 ]

4-Chloro-N-methyl-2-nitroaniline

Similarity: 0.71

Chemical Structure| 5344-44-5

[ 5344-44-5 ]

3-Chloro-5-nitroaniline

Similarity: 0.70

Chemical Structure| 619-10-3

[ 619-10-3 ]

2-Chloro-5-nitrophenol

Similarity: 0.69

Chemical Structure| 25781-92-4

[ 25781-92-4 ]

5-Chloro-2-nitro-N-phenylaniline

Similarity: 0.69