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[ CAS No. 369-34-6 ] {[proInfo.proName]}

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Chemical Structure| 369-34-6
Chemical Structure| 369-34-6
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Product Details of [ 369-34-6 ]

CAS No. :369-34-6 MDL No. :MFCD00007198
Formula : C6H3F2NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :RUBQQRMAWLSCCJ-UHFFFAOYSA-N
M.W : 159.09 Pubchem ID :123053
Synonyms :

Calculated chemistry of [ 369-34-6 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 35.18
TPSA : 45.82 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) : -5.67 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.36
Log Po/w (XLOGP3) : 2.25
Log Po/w (WLOGP) : 2.71
Log Po/w (MLOGP) : 1.73
Log Po/w (SILICOS-IT) : 0.55
Consensus Log Po/w : 1.72

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.58
Solubility : 0.417 mg/ml ; 0.00262 mol/l
Class : Soluble
Log S (Ali) : -2.85
Solubility : 0.226 mg/ml ; 0.00142 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.33
Solubility : 0.753 mg/ml ; 0.00473 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.82

Safety of [ 369-34-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P210-P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501 UN#:N/A
Hazard Statements:H315-H319-H335-H227 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 369-34-6 ]

* 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.

  • Upstream synthesis route of [ 369-34-6 ]
  • Downstream synthetic route of [ 369-34-6 ]

[ 369-34-6 ] Synthesis Path-Upstream   1~30

  • 1
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YieldReaction ConditionsOperation in experiment
93.8% With palladium on activated charcoal; hydrogen In toluene at 25 - 35℃; Autoclave Taken 200.Og of 3,4-difluoro nitro benzene, 600.Oml of Toluene and 12.Og of pd/C into autoclave at 25°C-35°C. Apply the Hydrogen gas 2.0-6.0Kg/Cm2 and maintained the reaction for 3-4 hrs at 25°C-35°C Check the reaction mass TLC to conform reactioncompletion. After reaction complies unload the reaction mass and filter through hyflow bed and wash with toluene (200.OmI). Take the filtrate and distilled under vacuum at below 50°C. the obtained 3,4-Difluoro aniline crude weight 152.Og,.Yield:93.8percent,purity by HPLC:95 .85percent.
77% With iron; ammonium chloride In methanol; water at 90℃; for 12 h; To a stirred solution of 1, 2-difluoro-4-nitrobenzene (4 g, 1 mmol) in methanol and water (25 mL: 5 mL) at RT, iron powder (2.5 g) and ammonium chloride (2 g) were added. The reaction mixture was refluxed for 12 h and the progress of reaction was monitored by TLC. After 12 h reaction time, the reaction mixture was filtered using celite pad. Then the solvent was evaporated under reduced pressure, water was added and the product was extracted with ethyl acetate and dried over anhydrous sodium sulphate. The crude product was purified by using column chromatography by eluting with ethyl acetate: hexane (30:70 v/v) which afforded the title compound in 77percent yield (2.5 g, brown liquid). 1H NMR (300 MHz, CDCl3): δ 6.88-6.94 (m, 1H, Ar-H), 6.43-6.47 (m, 1H, Ar-H), 6.31-6.34 (m, 1H, Ar-H), 3.60 (s, 2H, NH2). 13C NMR (75 MHz, CDCl3): δ 150.83, 147.60, 143.39, 140.02, 115.80, 108.57, 101.89. IR (CHCl3, νmax cm-1): 3383, 2360, 1617, 1521, 1266, 1213. MS (ESI, m/z) [M+H]+ 130.
43% With iron; ammonium chloride In methanol; water at 60℃; for 5 h; Heating / reflux Iron powder (28.1 g, 0.502 mol) was added as small portions to 1, 2-difluor nitrobenzene (20.0 g, 0.126 mol) in methanol (200 ML) and heated to 60 °C. Ammonium chloride (48.4 g, 0.91 mol) in water (100 ml) was added drop wise and the reaction mixture REFLUXED for 5 hr. The reaction mixture was filtered over Celite and washed with methanol. Methanol was removed, and the aqueous layer was extracted with ethylacetate, washed with brine, dried over sodium sulphate and concentrated to yield 1, 2-difluoro-4- aminobenzene (7 g, 43percent). [00147] BC13 (6.2 ML, 1M in DCM) was added drop wise to 1,2- DIFLUORO-4AMINOBENZENE (0.5 g, 0.004 mol) in trichloroethylene (6.5 ML) at 0°C and this mixture stirred for 15 min. 4-Cyanopyridine (0.48 g, 0.005 mol) was added and the solution was warmed to RT and stirred for 30 min. The solution was then heated at 80-90 °C for 1 h. The resulting solution was REFLUXED at 160°C for 4 hr and stirred at RT over night. 3N HCI was added to the reaction mixture and refluxed at 110 °C for 1.5 h. The reaction mixture was cooled to RT and made basic (pH = 12) with 6N NaOH. The reaction mixture was diluted with water and DCM. The resulting two layers were separated and the aqueous layer was extracted with DCM, dried over sodium sulphate and concentrated. The compound was purified by column chromatography using silica gel to yield title compound (0.25 g, 27percent).
Reference: [1] Patent: WO2015/68171, 2015, A1, . Location in patent: Page/Page column 9; 16
[2] Tetrahedron Letters, 2010, vol. 51, # 5, p. 786 - 789
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 2, p. 613 - 617
[4] ChemPlusChem, 2018, vol. 83, # 5, p. 375 - 382
[5] Synthesis, 2001, # 1, p. 81 - 84
[6] Patent: WO2004/46092, 2004, A2, . Location in patent: Page 48
[7] Journal of the American Chemical Society, 1951, vol. 73, p. 5884
[8] Journal of the American Chemical Society, 1959, vol. 81, p. 94,95, 97
[9] Journal of the American Chemical Society, 1959, vol. 81, p. 94,95, 97
[10] Molecular crystals and liquid crystals, 1984, vol. 112, # 3-4, p. 165 - 180
[11] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 23, p. 6492 - 6499
  • 2
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  • [ 7439-89-6 ]
  • [ 3863-11-4 ]
YieldReaction ConditionsOperation in experiment
86% With hydrogenchloride In methanol COMPARATIVE EXAMPLE 1
(Process wherein reduction and a diazochlorination method are used in combination)
10 g of 3,4-difluoronitrobenzene was dissolved in 20 and 2 g of methanol and 10 g of concentrated hydrochloric acid and 2 g of iron powder were added thereto.
The mixture was stirred at 60° C. for two hours, and then distilled to obtain 3,4-difluoroaniline.
The reduction yield was 86percent.
Reference: [1] Patent: US5208394, 1993, A,
  • 3
  • [ 369-34-6 ]
  • [ 403-19-0 ]
Reference: [1] Patent: US4224335, 1980, A,
  • 4
  • [ 99-54-7 ]
  • [ 369-34-6 ]
  • [ 350-30-1 ]
Reference: [1] Russian Journal of Organic Chemistry, 1994, vol. 30, # 12, p. 1925 - 1929[2] Zhurnal Organicheskoi Khimii, 1994, vol. 30, # 12, p. 1829 - 1832
[3] Chemistry Letters, 1990, # 5, p. 769 - 772
[4] Russian Journal of Organic Chemistry, 1994, vol. 30, # 12, p. 1925 - 1929[5] Zhurnal Organicheskoi Khimii, 1994, vol. 30, # 12, p. 1829 - 1832
  • 5
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Reference: [1] Molecular crystals and liquid crystals, 1984, vol. 112, # 3-4, p. 165 - 180
[2] Journal of the American Chemical Society, 1959, vol. 81, p. 94,95, 97
  • 6
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  • [ 455-93-6 ]
YieldReaction ConditionsOperation in experiment
91% at 10 - 20℃; for 2 - 3 h; Step 4:
Preparation of 3-fluoro-4-methoxyaniline (8)
Metallic sodium (1.45 grams, 63 mmol) was added slowly and portion wise to pre cooled (10° C.) methanol (100 mL) with stirring under nitrogen atmosphere.
The mixture was stirred at room temperature until all the sodium metal gets dissolved.
To this was added 3,4-difluoro nitrobenzene (6) (10 grams, 63 mmol) at room temperature and stirring continued at the same temperature for 2-3 hours.
The mixture was then concentrated under vacuum and poured into ice-water (100 mL).
The pH of the mixture was adjusted to ~7 by adding 2N HCl with stirring.
The solid separated was filtered off, washed with water and dried under vacuum to afford the product 2-fluoro-4-nitroanisol (7) (9.75 grams). Yield: 91percent; Melting point: 102-104° C.
64% With potassium hydroxide In dimethyl sulfoxide at 20℃; for 16 h; General procedure: A mixture of 2-fluorobenzamide (1a, 69.5 mg, 0.5 mmol), MeOH (ca. 32.0 mg, 1.0 mmol), KOH (56.0 mg, 1.0 mmol) and DMSO (2.0 mL) in a 25 mL screw-capped thick-walled Pyrex tube was stirred at room temperature for 16 h, and then water (10 mL) was added to the reaction mixture with stirring, and the mixture was extracted with ethyl acetate three times (3 * 10 mL). The combined organic phases were dried over Na2SO4 overnight. The filtered solution was concentrated under reduced pressure, and the crude residue was purified by column chromatography on silica gel with the use of petroleum ether/ethyl acetate/trimethylamine (gradient mixture ratio from 6:1:0.05 to 2:1:0.05 in volume) to afford 2aa as a white solid in 80percent yield (60.7 mg).
57% With sodium hydroxide In dimethyl sulfoxide at 20℃; for 12 h; 3,4-difluoronitrobenzene (31.88, 0.2111001), high purity NaOH (168,0.4111001), methanol (88,0.25mo 1), DMSO (200 mL) was added to the reactor and the reaction was stirred at 20 ° C for 12 hours. After completion of the reaction, 800 mL of ethyl acetate was added to the system and diluted 5 times with 200 mL of saturated brine. The organic phase was separated and dried over anhydrous sodium sulfateAfter which it was filtered, evaporated to dryness, and then it was loaded onto a silica gel column to separate petroleum ether: ethyl acetate = 4: 1 (volume) Was eluted as an eluent until the product appeared, the solution containing the product was collected and evaporated to dryness. After drying with a vacuum chestnut, 3-fluoro-4-methoxy nitrobenzene pure product, the yield of 57percent.
Reference: [1] Patent: US2006/128729, 2006, A1, . Location in patent: Page/Page column 77
[2] Tetrahedron, 2018, vol. 74, # 2, p. 303 - 307
[3] Patent: CN106565522, 2017, A, . Location in patent: Paragraph 0037; 0038
[4] Russian Chemical Bulletin, 2006, vol. 55, # 7, p. 1243 - 1247
  • 7
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  • [ 455-93-6 ]
Reference: [1] Inorganic Chemistry, 2016, vol. 55, # 5, p. 2274 - 2283
  • 8
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  • [ 369-34-6 ]
  • [ 6921-22-8 ]
  • [ 3862-73-5 ]
Reference: [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 11, p. 3203 - 3207[2] Angew. Chem., 2013, vol. 125, # 11, p. 3285 - 3289,5
  • 9
  • [ 97-00-7 ]
  • [ 369-34-6 ]
  • [ 364-74-9 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 7, p. 2010 - 2017
[2] Chemistry Letters, 1989, p. 2213 - 2216
  • 10
  • [ 98-95-3 ]
  • [ 402-67-5 ]
  • [ 369-34-6 ]
  • [ 364-74-9 ]
  • [ 350-46-9 ]
  • [ 1493-27-2 ]
YieldReaction ConditionsOperation in experiment
0.05 mmol at 0 - 25℃; Cooling with ice General procedure: A FEP or PFA reactor equipped with a Teflon-lined magnetic stir bar and connected to a gas-washing bottle was charged with substituted benzene (0.95–1.10 mmol), 1,1,1,3,3-pentafluorobutane (1–2 mL per mmol of C6H5R), and BF3 · Et2O (1.3–1.5 mmol per mmol of C6H5R). The mixture was stirred for 10–15 min at 0–5°C (ice bath), and XeF2 (1.2–1.3 mmol per mmol of C6H5R) was added in portions. After addition of each portion, the mixture was stirred for 3–5 min at 22–25°C and cooled again. When the addition was complete the dark solution was stirred for 15–30 min at 22–25°C, 10percent aqueous KHCO3 was added, and the upper organic layer was separated, passed through a short column charged with silica gel (40–60 μm), and dried over MgSO4. The solution was analyzed by 19F NMR and GC/MS. The main products are given in table, and the others are listed below (GC/MS data).
Reference: [1] Russian Journal of Organic Chemistry, 2016, vol. 52, # 10, p. 1400 - 1407[2] Zh. Org. Khim., 2016, vol. 52, # 10, p. 1412 - 1419,8
  • 11
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  • [ 1427-07-2 ]
Reference: [1] Synthesis, 2000, # 12, p. 1659 - 1661
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  • [ 369-35-7 ]
Reference: [1] Patent: US2436100, 1944, ,
[2] Patent: US2391179, 1942, ,
[3] Patent: US5310723, 1994, A,
  • 13
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  • [ 369-35-7 ]
Reference: [1] Patent: US2436100, 1944, ,
[2] Patent: US2391179, 1942, ,
  • 14
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  • [ 369-34-6 ]
  • [ 6921-22-8 ]
  • [ 3862-73-5 ]
Reference: [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 11, p. 3203 - 3207[2] Angew. Chem., 2013, vol. 125, # 11, p. 3285 - 3289,5
  • 15
  • [ 110-91-8 ]
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  • [ 93246-53-8 ]
Reference: [1] Organic Letters, 2008, vol. 10, # 10, p. 1935 - 1938
[2] Patent: US6362334, 2002, B1, . Location in patent: Page column 10-11
[3] Patent: WO2015/68121, 2015, A1, . Location in patent: Page/Page column 13; 14
  • 16
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  • [ 93246-53-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 6, p. 857 - 859
[2] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 4, p. 353 - 360
[3] J. Med. Chem., 1996, vol. 39, # 3, p. 673 - 679
[4] Patent: WO2011/77310, 2011, A1,
[5] Patent: WO2011/114210, 2011, A2,
[6] Patent: WO2011/137222, 2011, A1,
[7] Patent: US2011/275805, 2011, A1,
[8] Patent: EP2388251, 2011, A1,
[9] Patent: US2011/306606, 2011, A1,
[10] Turkish Journal of Chemistry, 2012, vol. 36, # 1, p. 37 - 53
[11] Patent: WO2012/114355, 2012, A1,
[12] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 5, p. 1143 - 1146,4
[13] Patent: WO2013/72923, 2013, A1,
[14] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 779 - 785
[15] Patent: US2013/324719, 2013, A1,
[16] Patent: WO2014/12360, 2014, A1,
[17] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 4, p. 874 - 880
[18] European Journal of Organic Chemistry, 2014, vol. 2014, # 34, p. 7614 - 7620
[19] Patent: US2015/87639, 2015, A1,
[20] Patent: TWI607995, 2017, B,
[21] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
[22] Patent: WO2015/162622, 2015, A1,
[23] Patent: CN103420933, 2016, B,
[24] Patent: CN102617500, 2016, B,
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[26] Journal of Medicinal Chemistry, 2018, vol. 61, # 9, p. 4052 - 4066
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[28] Patent: WO2005/103000, 2005, A1,
[29] Patent: EP2394993, 2011, A2,
[30] Patent: WO2008/122787, 2008, A1,
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Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 6, p. 857 - 859
[2] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 4, p. 353 - 360
[3] J. Med. Chem., 1996, vol. 39, # 3, p. 673 - 679
[4] Patent: WO2011/77310, 2011, A1,
[5] Patent: WO2011/114210, 2011, A2,
[6] Patent: WO2011/114210, 2011, A2,
[7] Patent: WO2012/114355, 2012, A1,
[8] Patent: WO2013/72923, 2013, A1,
[9] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 779 - 785
[10] Patent: US2013/324719, 2013, A1,
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[12] Patent: WO2015/68121, 2015, A1,
[13] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
[14] Patent: CN102617500, 2016, B,
  • 18
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  • [ 154590-66-6 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 19, p. 4261 - 4267
[2] Patent: WO2011/37731, 2011, A1,
[3] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 16, p. 4490 - 4498
[4] Patent: CN107033095, 2017, A,
  • 19
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  • [ 174649-09-3 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 4, p. 353 - 360
[2] J. Med. Chem., 1996, vol. 39, # 3, p. 673 - 679
[3] Patent: WO2011/77310, 2011, A1,
[4] Patent: WO2011/114210, 2011, A2,
[5] Patent: WO2011/114210, 2011, A2,
[6] Patent: WO2012/114355, 2012, A1,
[7] Patent: WO2013/72923, 2013, A1,
[8] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 779 - 785
[9] Patent: US2013/324719, 2013, A1,
[10] Patent: WO2015/68121, 2015, A1,
[11] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
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Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 19, p. 4261 - 4267
[2] Patent: US2011/306606, 2011, A1,
[3] European Journal of Medicinal Chemistry, 2014, vol. 75, p. 43 - 56
[4] Patent: US2014/121200, 2014, A1,
[5] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
[6] Patent: CN107033095, 2017, A,
[7] Chemical Papers, 2018, vol. 72, # 2, p. 457 - 468
[8] Patent: EP2394993, 2011, A2,
  • 21
  • [ 369-34-6 ]
  • [ 57260-71-6 ]
  • [ 154590-35-9 ]
Reference: [1] Patent: WO2011/37731, 2011, A1,
  • 22
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  • [ 57260-71-6 ]
  • [ 154590-34-8 ]
YieldReaction ConditionsOperation in experiment
97% With potassium carbonate In N,N-dimethyl-formamide at 90 - 95℃; for 18 h; Step A. 4-(2-Fluoro-4-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester. A mixture of piperazine-1 -carboxylic acid tert-butyl ester (10.0 g, 53.7 mmol), 3,4-difluoronitrobenzene (6.0 ml_, 54.2 mmol) and K2CO3 (22.0 g, 159 mmol) in DMF (60.00 mL) was heated to about 90-950C for 18 h. The resulting mixture was cooled to room temperature and diluted with ethyl acetate (700.0 mL) and water (200.0 mL). The organic phase was separated and washed with water (3x300 mL), dried (Na2SO4), filtered and concentrated to yield a yellow solid (17.0O g, 97 percent). 1H NMR (CDCI3): 8.01 -7.96 (m, 1 H), 7.95-7.88 (m, 1 H), 6.90 (t, J = 8.8, 1 H), 3.65-3.55 (m, 4H), 3.28-3.20 (m, 4H), 1.48 (s, 9H).
91% With potassium carbonate In N,N-dimethyl-formamide at 5℃; To an ice cold (5 °C) solution of piperazine-l -carboxylic acid tert-butyl ester (17.56 g, 94.28 mmol) in dry DMF (50 mL) was added K2CO3 (12.8 g, 94.28 mmol) and the slurry stirred for 15 minutes. 1 ,2-Difluoro-4-nitro-benzene (15.0 g, 94.28 mmol) was added to the slurry and the reaction mixture stirred vigorously for 2 h. The mixture was filtered and the insoluble material washed with DMF (25 mL). The combined filtrate was evaporated to dryness under reduced pressure, and the yellow solid that formed was re-crystallized from DCM to affording 30.1 g (91percent) of the title compound. 1H NMR (400 MHz, DMSO-i/6) δ (ppm): 8.04 - 7.99 (m, 2H), 7.17 (t, J= 9.0 Hz, 1H), 3.48 (t, J = 4.8 Hz, 4H), 3.25 (t, J= 5.2 Hz, 4H), 1.42 (s, 9H); l 9F NMR (376 MHz, DMSO-4 δ (ppm): - 1 19.79 (dd, J = 13.8, 9.0 Hz).
91% With triethylamine In methanol at 50 - 60℃; for 17 h; 3-4-1:
Preparation of [3-fluoro-4-BOC-piperazino)]nitrobenzene
To 100 ml of methanol were sequentially added 5 g (31.4 mmol) of 3,4-difluoronitrobenzene, 5.3 ml (37.7 mmol) of triethylamine and 6.4 g (34.5 mmol) of Boc-piperazine, followed by reaction at a temperature of 50 to 60° for 17 hours.
After the reaction was complete, the reaction liquid was cooled to room temperature and 20 ml of water was slowly added dropwise thereto, followed by stirring for 4 hours.
The resulting solid was filtered, washed with a 1:1 (v/v) solution of water and methanol and then dried under vacuum at about 40° to afford 9.3 g (yield: 91percent) of the desired compound.
1H-NMR (DMSO-d6): 1.42(s, 9H), 3.25(m, 4H), 3.48(m, 4H), 7.18(3, 1H), 8.03(m, 2H).
91% With triethylamine In methanol at 50 - 60℃; for 17 h; Example 3-4-1 Preparation of [3-fluoro-4-(BOC-piperazino)]nitrobenzene To 100ml of methanol were sequentially added 5g (31.4mmol) of 3,4-difluoronitrobenzene, 5.3ml (37.7mmol) of triethylamine and 6.4g (34.5mmol) of BOC-piperazine, followed by reaction at a temperature of 50 to 60°C for 17 hours. After the reaction was complete, the reaction liquid was cooled to room temperature and 20ml of water was slowly added dropwise thereto, followed by stirring for 4 hours. The resulting solid was filtered, washed with a 1:1 (v/v) solution of water and methanol and then dried under vacuum at about 40°C to afford 9.3g (yield: 91percent) of the desired compound. 1H-NMR (DMSO-d6): 1.42(s, 9H), 3.25(m, 4H), 3.48(m, 4H), 7.18(3,1H), 8.03(m, 2H).
72% for 16 h; Heating / reflux Preparation 57; 4-(2-Fluoro-4-nitro-phenyl)-piperazine- 1 -carboxylic acid tert-bvXyl ester; Dissolve 3,4-difluoronitrobenzene (2.0 g, 12.6 mmol) in acetonitrile (35 mL) and add piperazine-1 -carboxylic acid tert-bvAyl ester (4.7 g, 25.2 mmol). Heat the mixture at reflux for 16 h. Cool the mixture to room temperature and concentrate in vacuo. Partition the residue between dichloromethane (75 mL) and water (75 mL), separate the organic portion and extract the aqueous portion with dichloromethane (2 x 25 mL).Combine the organics and dry (Na2SO4), filter, and concentrate in vacuo to give 2.83 g (72percent) of the title compound. MS/ES m/z 270.2 [M-tertBu+H]+.

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[9] Patent: US2014/121200, 2014, A1, . Location in patent: Paragraph 0251; 0252
[10] Chemical Papers, 2018, vol. 72, # 2, p. 457 - 468
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Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 19, p. 4261 - 4267
[2] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
[3] Patent: CN107033095, 2017, A,
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  • [ 369-34-6 ]
  • [ 337529-74-5 ]
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[2] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 24, p. 6674 - 6679
[3] Patent: CN108069919, 2018, A,
[4] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 814 - 831
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[2] Patent: WO2014/12360, 2014, A1,
[3] European Journal of Medicinal Chemistry, 2014, vol. 75, p. 43 - 56
[4] Patent: WO2014/151871, 2014, A2,
[5] Patent: US2015/87639, 2015, A1,
[6] Patent: TWI607995, 2017, B,
  • 27
  • [ 369-34-6 ]
  • [ 105-53-3 ]
  • [ 315228-19-4 ]
Reference: [1] Patent: CN103360379, 2017, B, . Location in patent: Paragraph 0150-0151
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  • [ 369-34-6 ]
  • [ 315228-19-4 ]
Reference: [1] Patent: WO2013/29338, 2013, A1,
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[2] Organic Process Research and Development, 2018, vol. 22, # 3, p. 409 - 419
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[2] Patent: WO2017/156181, 2017, A1,
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