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[ CAS No. 875-51-4 ] {[proInfo.proName]}

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Chemical Structure| 875-51-4
Chemical Structure| 875-51-4
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Product Details of [ 875-51-4 ]

CAS No. :875-51-4 MDL No. :MFCD00041312
Formula : C6H5BrN2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :ZCWBZRBJSPWUPG-UHFFFAOYSA-N
M.W : 217.02 Pubchem ID :70132
Synonyms :

Calculated chemistry of [ 875-51-4 ]

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 : 47.37
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) : -6.27 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.35
Log Po/w (XLOGP3) : 1.9
Log Po/w (WLOGP) : 1.95
Log Po/w (MLOGP) : 1.05
Log Po/w (SILICOS-IT) : -0.33
Consensus Log Po/w : 1.18

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.72
Solubility : 0.413 mg/ml ; 0.0019 mol/l
Class : Soluble
Log S (Ali) : -3.03
Solubility : 0.202 mg/ml ; 0.00093 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.28
Solubility : 1.14 mg/ml ; 0.00527 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 3.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.25

Safety of [ 875-51-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H317-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 875-51-4 ]

* 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.

  • Upstream synthesis route of [ 875-51-4 ]
  • Downstream synthetic route of [ 875-51-4 ]

[ 875-51-4 ] Synthesis Path-Upstream   1~39

  • 1
  • [ 875-51-4 ]
  • [ 1758-73-2 ]
  • [ 4887-88-1 ]
YieldReaction ConditionsOperation in experiment
68% With sodium hydroxide In ethanol; water at 70℃; for 1.5 h; Green chemistry General procedure: TUD (20 mmol) was added in batches to a solution of substituted 2‑nitroanilines (5 mmol) and NaOH (20 mmol) in H2O (15 mL) and EtOH (5 mL) at 70 °C. The reaction mixture was stirred for a certain period of time as required to complete the reaction (monitored byTLC). After cooling, 10percent NaOH solutions were added until pH = 9–10, the precipitated solid was filtered off and washed with water to obtain crude product. The crude product was recrystallised from water to give a white solid. The physical and spectra data of the compounds 2a–h were as follows.
Reference: [1] Journal of Chemical Research, 2014, vol. 38, # 2, p. 118 - 120
  • 2
  • [ 875-51-4 ]
  • [ 4887-88-1 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 827 - 832
  • 3
  • [ 1445-45-0 ]
  • [ 875-51-4 ]
  • [ 1964-77-8 ]
YieldReaction ConditionsOperation in experiment
90% With indium; acetic acid In ethyl acetate for 4 h; 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 10percent NaHCO3 (30 mL), and then extracted with ethyl acetate (30 mL.x.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.
Reference: [1] Tetrahedron, 2011, vol. 67, # 41, p. 8027 - 8033
  • 4
  • [ 875-51-4 ]
  • [ 57339-57-8 ]
Reference: [1] Monatshefte fuer Chemie, 1994, vol. 125, # 6/7, p. 723 - 730
  • 5
  • [ 875-51-4 ]
  • [ 52415-29-9 ]
Reference: [1] Chemical & Pharmaceutical Bulletin, 1987, vol. 35, # 5, p. 1823 - 1828
  • 6
  • [ 875-51-4 ]
  • [ 32046-62-1 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 827 - 832
  • 7
  • [ 875-51-4 ]
  • [ 51376-06-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 2, p. 233 - 235
[2] Russian Chemical Bulletin, 2011, vol. 60, # 11, p. 2306 - 2314[3] Izv. Akad. Nauk, Ser. Khim., 2011, # 11, p. 2262 - 2269,8
[4] Organic Process Research and Development, 2003, vol. 7, # 3, p. 436 - 445
[5] Organic Process Research and Development, 2003, vol. 7, # 3, p. 436 - 445
[6] European Journal of Medicinal Chemistry, 2018, vol. 155, p. 754 - 763
[7] Patent: WO2009/158393, 2009, A1,
  • 8
  • [ 875-51-4 ]
  • [ 139399-64-7 ]
Reference: [1] Monatshefte fuer Chemie, 1994, vol. 125, # 6/7, p. 723 - 730
  • 9
  • [ 875-51-4 ]
  • [ 107-21-1 ]
  • [ 68527-67-3 ]
YieldReaction ConditionsOperation in experiment
33% With sulfuric acid; sodium 3-nitrobenzenesulfonate In water at 135℃; for 3 h; A sulfuric acid solution was prepared by adding H2SO4 (50 mL) to an 250 mL flask containing H2O (20 mL) cooled in an ice bath. To this solution was added glycerol (12 mL, 16.5 mmol), m-nitrobenzene sulfonic acid sodium salt (11.4 g, 5.06 mmol), and 4-bromo-2-nitrophenylamine (10 g, 4.6 mmol). The reaction mixture was heated at 135°C for 3 hours. The warm reaction mixture was poured into ice H2O (200 mL) and extracted into 50percent MeOH/EtOAc (2 x 200 mL), dried over Na2SO4 and concentrated. The resulting brown solid was triturated with EtOH and filtered affording 3.8 g (33percent) of a pink solid: mp 172-174°C.
Reference: [1] Patent: EP1147083, 2004, B1, . Location in patent: Page 45-46
  • 10
  • [ 875-51-4 ]
  • [ 56-81-5 ]
  • [ 68527-67-3 ]
YieldReaction ConditionsOperation in experiment
46% at 150℃; for 0.75 h; Inert atmosphere General procedure: To glycerol (4.7 mL, 62.0 mmol) preheated to 160 C for 1 hour, and cooled down to 110 C, 4-bromo-2-nitroaniline (5.00 g, 23.0 mmol) and sodium iodide (0.07 g, 0.48 mmol) were added. The mixture was vigorously stirred, heated to 150 C and sulfuric acid 95-98percent (2.8 ml, 53.0 mmol) was added drop wise. After 45 minutes at 150 C, the mixture was allowed to reach room temperature, and then distributed in DCM and water. The organic layer was separated, washed with water, brine solution, dried over Na2SO4 and evaporated. The crude product was purified through column chromatography to give 21 compound (2.6 g, 46percent); 1H NMR (300 MHz, DMSO-d6): δ 9.06 (d, J = 4.3 Hz, 1H), 8.52-8.66 (m, 3H), 7.79 (dd, J = 8.4, 4.2 Hz, 1H); LCMS (m/z) = 253 [M+1]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 5, p. 1100 - 1103
[2] Monatshefte fuer Chemie, 1994, vol. 125, # 6/7, p. 723 - 730
  • 11
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  • [ 337915-79-4 ]
Reference: [1] Patent: US2014/275025, 2014, A1,
  • 12
  • [ 875-51-4 ]
  • [ 69038-76-2 ]
Reference: [1] Patent: WO2014/140075, 2014, A1,
  • 13
  • [ 875-51-4 ]
  • [ 19155-88-5 ]
Reference: [1] Patent: WO2009/158393, 2009, A1,
  • 14
  • [ 875-51-4 ]
  • [ 1575-37-7 ]
YieldReaction ConditionsOperation in experiment
94% With stannous chloride In ethanol a.
4-Bromo-o-phenylenediamine. 4-Bromo-2-nitroaniline 600 mg (2.76 mmol) was dissolved in 25 ml absolute ethanol and 2.72 g (14 mmol) SnCl2 was added.
The mixture was refluxed overnight.
Ethanol was removed in vacuo and the mixture basified with 2N NaOH to pH 11.
Ether extraction, drying the ether layer over anhydrous Na2 SO4 and concentration in vacuo afforded 486 mg (2.6 mmol, 94percent yield) of the crude 4-bromo-o-phenylenediamine which was used for the next step without characterization.
94% With stannous chloride In ethanol (D)
4-Bromophenylenediamine (JSK IV-35)
To 2-nitro-4-bromoaniline (340 mg, 1.57 mmol) in absolute ethanol (20 mL) was added SnCl2 (1.50g, 7.91 mmol) and refluxed overnight.
The reaction mixture was then basified to pH 11 with 2N NaOH and extracted with ether to give 275 mg (94percent) of product.
This product was used without further purification for the synthesis of JSK IV-37.
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 827 - 832
[2] Australian Journal of Chemistry, 1983, vol. 36, # 11, p. 2317 - 2325
[3] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 11, p. 2591 - 2600
[4] Patent: US6063801, 2000, A,
[5] Journal of Organic Chemistry, 2007, vol. 72, # 9, p. 3186 - 3193
[6] Angewandte Chemie - International Edition, 2011, vol. 50, # 16, p. 3803 - 3806
[7] RSC Advances, 2015, vol. 5, # 113, p. 93194 - 93208
[8] Heterocycles, 1987, vol. 26, # 9, p. 2433 - 2442
[9] Organic Preparations and Procedures International, 2000, vol. 32, # 5, p. 485 - 488
[10] Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, vol. 29, # 2, p. 281 - 291
[11] Journal of Polymer Science, Part A: Polymer Chemistry, 2012, vol. 50, # 11, p. 2172 - 2181
[12] Justus Liebigs Annalen der Chemie, 1881, vol. 209, p. 358
[13] Journal of the Chemical Society, 1949, p. 1271,1275
[14] Bioorganic and Medicinal Chemistry, 1998, vol. 6, # 2, p. 163 - 172
[15] Russian Journal of General Chemistry, 1998, vol. 68, # 4, p. 620 - 629
[16] Archiv der Pharmazie, 2000, vol. 333, # 5, p. 123 - 129
[17] Patent: US2004/92521, 2004, A1, . Location in patent: Page/Page column 45
[18] Patent: US2003/28018, 2003, A1,
[19] Patent: US2002/107392, 2002, A1,
[20] Patent: US5770617, 1998, A,
[21] Patent: US2004/224953, 2004, A1,
[22] Patent: US2005/256157, 2005, A1,
[23] Patent: US2005/261307, 2005, A1,
[24] Patent: US2008/300247, 2008, A1, . Location in patent: Page/Page column 38
[25] Patent: WO2004/18419, 2004, A2, . Location in patent: Page 279
[26] Patent: US2003/199511, 2003, A1, . Location in patent: Page/Page column 74
[27] Patent: US2004/224952, 2004, A1, . Location in patent: Page 41
[28] Patent: US2004/248899, 2004, A1, . Location in patent: Page 33
[29] Patent: US2009/326029, 2009, A1, . Location in patent: Page/Page column 33
[30] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 17, p. 4790 - 4793
[31] Journal of the Serbian Chemical Society, 2014, vol. 79, # 3, p. 277 - 282
[32] Science China Chemistry, 2015, vol. 58, # 7, p. 1152 - 1158
[33] Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6289 - 6304
[34] Patent: WO2007/143456, 2007, A2, . Location in patent: Page/Page column 88
  • 15
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  • [ 1575-37-7 ]
Reference: [1] Patent: US2003/187026, 2003, A1,
  • 16
  • [ 875-51-4 ]
  • [ 68468-39-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6289 - 6304
  • 17
  • [ 875-51-4 ]
  • [ 6393-40-4 ]
YieldReaction ConditionsOperation in experiment
39.1% for 20 h; Reflux; Inert atmosphere A mixture of 20 g (92.2 mmol) of 4-bromo-2-nitroaniline and 20.8 g of cuprous cyanide were dissolved in 150 ml of N, N-dimethylformamide (DMF) The reaction was refluxed for 20 hours in a nitrogen atmosphere, cooled in ice water, extracted with ethyl acetate, concentrated and recrystallized. The drying weight was 5.88 g (yield 39.1percent)
Reference: [1] Patent: CN103896849, 2017, B, . Location in patent: Paragraph 0045
  • 18
  • [ 875-51-4 ]
  • [ 20358-03-6 ]
Reference: [1] Journal of the Chemical Society [Section] C: Organic, 1969, p. 268 - 272
  • 19
  • [ 88-74-4 ]
  • [ 59255-95-7 ]
  • [ 875-51-4 ]
YieldReaction ConditionsOperation in experiment
74% at 34.84 - 89.84℃; for 5.5 h; To a solution of 2-nitroaniline (34.5 g, 0.25 mol) in aceticacid (400 ml), N-bromosuccinimide (44.5 g, 0.25 mol) wasadded portionwise over a period of 30 min at 308–318 K(Fig. 1). The mixture was stirred for 3 h at 318 K, warmed to363 K and stirred for 2 h. After cooling the mixture to roomtemperature, it was poured into intensively stirred cold water (4 l). After 10 min, an orange precipitate was filtered off andwashed with water (2 200 ml). The obtained crude productwas recrystallized from 80percent EtOH and dried under vacuum togive pure 4-bromo-2-nitroaniline (yield 39.9 g, 74percent) as anorange crystalline solid. From the filtrate, a second crystallizationcrop was obtained (yield 6.81 g), comprised of 4-bromo-2-nitroaniline and 2-bromo-6-nitroaniline in a 1:0.3ratio. The NMR spectra are consistent with those published inthe literature (Manley et al., 2003; Lemaire et al., 1989). Analytical data for 4-bromo-2-nitroaniline, 1H NMR(300 MHz, CDCl3): 8.26 (dd, J = 2.3, 0.4 Hz, 1H), 7.42 (dd, J =8.9, 2.3 Hz, 1H), 6.73 (dd, J = 8.9, 0.4 Hz, 1H), 6.10 (s, 2H).Analytical data for 2-bromo-6-nitroaniline, 1H NMR(400 MHz, CDCl3): 8.14 (dd, J = 8.7, 1.5 Hz, 1H), 7.70 (dd, J =7.7, 1.5 Hz, 1H), 6.63 (s, 2H), 6.62 (dd, J = 8.7, 7.7 Hz, 1H).Single crystals of 4-bromo-2-nitroaniline were obtained byslow evaporation from chloroform and of 2-bromo-6-nitroanilineby sublimation of the second crystallization crop underreduced pressure (323 K, 10 mbar; 1 bar = 105 Pa).
Reference: [1] Polyhedron, 2013, vol. 52, p. 246 - 254
[2] Synthetic Communications, 2000, vol. 30, # 20, p. 3669 - 3675
[3] Acta Crystallographica Section C: Structural Chemistry, 2018,
[4] Synthetic Communications, 2004, vol. 34, # 12, p. 2143 - 2152
[5] Tetrahedron Letters, 2012, vol. 53, # 2, p. 127 - 131
  • 20
  • [ 88-74-4 ]
  • [ 59255-95-7 ]
  • [ 875-51-4 ]
  • [ 827-23-6 ]
Reference: [1] Tetrahedron Letters, 2000, vol. 41, # 13, p. 2083 - 2085
  • 21
  • [ 88-74-4 ]
  • [ 20691-72-9 ]
  • [ 875-51-4 ]
Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 28, p. 4793 - 4796
  • 22
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  • [ 16588-24-2 ]
Reference: [1] Recueil des Travaux Chimiques des Pays-Bas, 1915, vol. 34, p. 205
  • 23
  • [ 875-51-4 ]
  • [ 108-24-7 ]
  • [ 881-50-5 ]
YieldReaction ConditionsOperation in experiment
99.1% at 95℃; for 7.5 h; 4-Bromo-2-nitroaniline 3a (30.3 g, 138 mmol) was dissolved in 240 mL of acetic acid, and acetic anhydride (22.44g, 220.2 mmol) was added, and the mixture was heated to 95 ° C for 7.5 hours. The reaction solution was cooled to room temperature and poured into 600 mL of ice water. After ice-melting, it was extracted with dichloromethane (90 mL×3), and the solid was dissolved in dichloromethane (600 mL), the organic phase was combined, dried over anhydrous sodium sulfate Concentration gave N-(4-bromo-2-nitrophenyl)acetamide 3b (35.4g, orange solid), yield: 99.1percent.
67.9% With acetic acid In dichloromethane at 95℃; for 6 h; A mixture of 4-bromo-2-nitroaniline 1a (100g, 460.79mmol) was dissolved in 10mL of dichloromethane, was added 1000mL of acetic acid, acetic anhydride (61.15g, 599.02mmol), was heated to 95 deg.] C for 5 hours.The unreacted starting material completely, additional acetic anhydride (4.70g, 46.08mmol), the reaction was continued 95 1 hour.The reaction was cooled to room temperature was added 2000mL of water, filtered, to the filtrate was added 500mL of water, filtered again, the filtrate was added 500mL of water was filtered again, all solids were combined, washed with 1000mL water and 1000mL saturated sodium bicarbonate solution, two solid was dissolved in 500mL chloride, and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give N- (4- bromo-2-nitrophenyl) acetamide 8a (162g, orange solid), yield: 67.9percent
Reference: [1] Patent: CN108264511, 2018, A, . Location in patent: Paragraph 0243; 0246-0249
[2] European Journal of Organic Chemistry, 2009, # 32, p. 5647 - 5652
[3] Patent: US6369232, 2002, B1, . Location in patent: Page column 60
[4] Patent: CN107400092, 2017, A, . Location in patent: Paragraph 0393; 0396-0399
[5] Journal of the Chemical Society. Perkin Transactions 1, 2001, # 21, p. 2754 - 2756
[6] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 7, p. 2156 - 2167
  • 24
  • [ 875-51-4 ]
  • [ 75-36-5 ]
  • [ 881-50-5 ]
YieldReaction ConditionsOperation in experiment
81% With pyridine; acetic anhydride In tetrahydrofuran; diethyl ether; water EXAMPLE 20
(E)-3-Cyclopentyl-2-[3-methanesulfonyl-4-(5-methyl-tetrazol-1-yl)-phenyl]-N-thiazol-2-yl-acrylamide
A solution of 2-nitro-4-bromoaniline (7.07 g, 32.6 mmol) in dry tetrahydrofuran (33 mL) was cooled to 0° C. and then treated with acetic anhydride (6.66 g, 65.2 mmol).
The reaction mixture was stirred at 0° C. for 10 min and then allowed to warm to 25° C.
The reaction mixture was stirred at 25° C. for 15 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the presence of only starting material.
The reaction mixture was then slowly treated with acetyl chloride (5 mL) and pyridine (5 mL) at 25° C.
The resulting orange suspension was stirred at 25° C. for 2 h and then treated with water (50 mL).
The organic compound was extracted into ethyl acetate (2*70 mL).
The combined extracts were washed with a 3N aqueous hydrochloric acid solution (1*100 mL) and a saturated aqueous sodium chloride solution (1*100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford a yellow solid.
The yellow solid was treated with diethyl ether (50) mL) and hexanes (50 mL).
The solid was collected by filtration and washed with hexanes to afford N-(4-bromo-2-nitro-phenyl)-acetamide (6.82 g, 81percent) as a yellow solid: mp 100-102° C.; EI-HRMS m/e calcd for C8H7BrN2O3 (M+) 257.9640, found 257.9641.
Reference: [1] Patent: US2002/35266, 2002, A1,
  • 25
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  • [ 20776-50-5 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1891, vol. <2> 43, p. 204
  • 26
  • [ 875-51-4 ]
  • [ 610-38-8 ]
YieldReaction ConditionsOperation in experiment
76% at 0 - 50℃; To a cold solution of trifluoroacetic acid (25 mL) at 0° C. was added compound 8 (4.96 g, 22.96 mmol). After being stirred for 10 minutes, a solution of 33percent hydrogen peroxide (13.75 mL, 133 mmol) was added, and the mixture was stirred at room temperature for 0.5 h, followed by stirring at 50° C. for 2 h. The mixture was poured into ice water, and the solid obtained was filtered and washed with cold water to get the titled compound 24. Yield: 76percent, yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.85-7.92 (m, 2H, H-5, H-6), 8.04 (br. s, 1H, H-3). I3C NMR (125.7 MHz, CDCl3) δ 126.39 (C-2), 127.91 (C-3), 128.09 (C-4), 136.29 (C-5), 141.26 (C-1), 143.42 (C-2). Anal. Calcd for C6H3BrN2O4: C, 29.18; 11, 1.22; N, 11.34percent. Found: C, 29.12; II, 1.26; N, 11.26percent.
Reference: [1] Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, vol. 29, # 2, p. 281 - 291
[2] Patent: US8901304, 2014, B1, . Location in patent: Page/Page column 12
  • 27
  • [ 875-51-4 ]
  • [ 99277-71-1 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1891, vol. <2> 43, p. 204
  • 28
  • [ 40101-31-3 ]
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  • [ 53324-38-2 ]
Reference: [1] Journal of the Chemical Society, 1930, p. 928,933
  • 29
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  • [ 16429-44-0 ]
Reference: [1] Patent: WO2016/16421, 2016, A1,
  • 30
  • [ 875-51-4 ]
  • [ 17626-40-3 ]
Reference: [1] Patent: CN103896849, 2017, B,
  • 31
  • [ 875-51-4 ]
  • [ 112671-42-8 ]
YieldReaction ConditionsOperation in experiment
88%
Stage #1: With boron trifluoride diethyl etherate In tetrahydrofuran at -30℃; for 0.5 h;
Stage #2: With tert.-butylnitrite In tetrahydrofuran; diethyl ether at -30 - -5℃; for 1.25 h;
Stage #3: With iodine; potassium iodide In acetonitrile at 20℃; for 1.3 h;
To BF3·OEt2 (16.0 mL, 126.3 mmol) at –30 °C was added a solution of 4-bromo-2-nitroaniline (6.50g, 30.0 mmol) in THF (100 mL) dropwise over 20 min. The mixture was stirred at –30 °C for 10 min andthen a solution of tBuONO (13.0 mL, 90percent, 109.3 mmol) in THF (81 mL) was added dropwise over 15min. The reaction mixture was allowed to warm to –10 °C at which time Et2O (158 mL) was addeddropwise. The mixture was allowed to stir at –5 °C for 1 h until a white pale solid precipitated. The solidwas filtered and washed with Et2O to afford a white solid which was then added in one portion to a 500mL round-bottomed flask containing, KI (5.45 g, 26.53 mmol), iodine (7.16 g, 13.27 mmol), and MeCN(120 mL). The mixture was stirred at RT for 1.3 h, quenched with sat. aq Na2S2O3 (250 mL), and22extracted with CH2Cl2 (2 x 150 mL). The organic layers were combined, dried over Na2SO4, andconcentrated in vacuo to afford 4-bromo-1-iodo-2-nitrobenzene (8.61 g, 88percent yield) as a yellow solid.
Reference: [1] Biochemistry, 2018, vol. 57, # 18, p. 2733 - 2743
[2] Heterocycles, 2009, vol. 79, # C, p. 805 - 820
[3] Tetrahedron, 2013, vol. 69, # 45, p. 9481 - 9493
[4] Journal of Medicinal Chemistry, 2018, vol. 61, # 13, p. 5547 - 5568
[5] Synthesis, 2008, # 13, p. 2039 - 2044
[6] Journal of Organic Chemistry, 2004, vol. 69, # 5, p. 1752 - 1755
[7] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[8] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
[9] Chemical & Pharmaceutical Bulletin, 1987, vol. 35, # 5, p. 1823 - 1828
[10] Patent: WO2017/20086, 2017, A1, . Location in patent: Page/Page column 62; 71
[11] Tetrahedron, 2017, vol. 73, # 34, p. 5072 - 5081
[12] Organic Letters, 2017, vol. 19, # 17, p. 4484 - 4487
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  • [ 79603-03-5 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1891, vol. <2> 43, p. 204
  • 33
  • [ 875-51-4 ]
  • [ 180624-08-2 ]
YieldReaction ConditionsOperation in experiment
88% With iodine; silver sulfate In ethanol at 20℃; for 18 h; 4-Bromo-2-iodo-6-nitroaniline.4-Bromo-2-nitroaniline (14.3g, 0.0659 mol) was added in one portion to iodine (17.6g, 0.0692 mol) dissolved in ethanol (30OmI)1 followed by silver (I) sulphate (20.4g 0.0659 mol). After stirring at ambient temperature for 18 hours the reaction was <n="16"/>filtered and the solid obtained was washed with dichloromethane until all the orange product had dissolved. The combined filtrates were evaporated in vacuo and the resulting solid was washed with diethyl ether/ 40-60 Petroleum ether (1 :1 ) and filtered to give 4-bromo-2-iodo-6-nitroaniline as an orange solid (19.8 g, 88percent), which was used without further purification. 1H NMR (400MHz,δ,CDCI3): 6.15(2H,br s), 8.00(1 H,s), 8.42(1 H,s).
81% With iodine; silver sulfate In ethanol at 20℃; 4-bromo-2-nitroaniline (1.4 g, 6.45 mmol) was added to iodine (1.801 g, 7.10 mmol) in EtOH (30 mL), followed by silver sulfate (2.213 g, 7.10 mmol). The reaction mixture was stirred at room temperature overnight and filtered. The solid was washed with EtOAc. The filtrate was concentrated. The crude product was dissolved in a small amount of chloroform and charged to a 120 g silica gel cartridge which was eluted with 5percent for 3 min., then an 18 min gradient from 5percent to 40percent. The desired fractions were combined and concentrated to give Intermediate 1A (1.8 g, 5.25 mmol, 81percent yield) as a brown solid. H1 NMR (500 MHz, methanol-d4) δ 8.25(d, J=2.2 Hz, 1H), 8,04(d, J=2.2 Hz, 1H); LC-MS: method A, RT=2.08 min; No MS (ESI) was observed;
Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 17, p. 5804 - 5812
[2] Patent: WO2007/148093, 2007, A1, . Location in patent: Page/Page column 14-15
[3] Journal of Organic Chemistry, 2018, vol. 83, # 17, p. 10627 - 10635
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[5] Patent: WO2017/19828, 2017, A1, . Location in patent: Page/Page column 57
[6] Journal of the Chemical Society, 1928, p. 783
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[3] Patent: WO2017/20086, 2017, A1,
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[2] Patent: WO2014/160221, 2014, A1,
[3] European Journal of Medicinal Chemistry, 2015, vol. 96, p. 340 - 359
[4] Patent: US9365498, 2016, B2,
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