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Product Details of [ 656-65-5 ]

CAS No. :656-65-5 MDL No. :MFCD00672933
Formula : C6H5BrFN Boiling Point : -
Linear Structure Formula :- InChI Key :YTMVYYAKOPIJCZ-UHFFFAOYSA-N
M.W : 190.01 Pubchem ID :821848
Synonyms :

Calculated chemistry of [ 656-65-5 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 38.5
TPSA : 26.02 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.02 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.65
Log Po/w (XLOGP3) : 2.03
Log Po/w (WLOGP) : 2.6
Log Po/w (MLOGP) : 2.67
Log Po/w (SILICOS-IT) : 2.25
Consensus Log Po/w : 2.24

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.79
Solubility : 0.308 mg/ml ; 0.00162 mol/l
Class : Soluble
Log S (Ali) : -2.2
Solubility : 1.19 mg/ml ; 0.00625 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.17
Solubility : 0.128 mg/ml ; 0.000673 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.33

Safety of [ 656-65-5 ]

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

Application In Synthesis of [ 656-65-5 ]

* 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 [ 656-65-5 ]
  • Downstream synthetic route of [ 656-65-5 ]

[ 656-65-5 ] Synthesis Path-Upstream   1~16

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Reference: [1] Synthesis, 2009, # 8, p. 1305 - 1308
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YieldReaction ConditionsOperation in experiment
100% With hydrogenchloride; water In ethanol at 80℃; for 4 h; To a stirred solution of N-(4-bromo-3-fluorophenyl)acetamide (12.9 g, 12.9 mmol) dissolved in ethanol (30 mL), conc. HCI (15 mL) was added and refluxed at 80 °C for4 h. The reaction mixture diluted ice water and extracted with ethyl acetate, the combined organic layer was washed with water and brine solution. The solvent was removed under vacuo to yield the title compound (2.45 g, 100.0percent) as an off white solid.
Reference: [1] Patent: WO2014/202580, 2014, A1, . Location in patent: Page/Page column 97; 98
[2] Molecular Crystals and Liquid Crystals (1969-1991), 1991, vol. 204, p. 43 - 64
[3] Journal of the Chemical Society, 1958, p. 2815,2818
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Reference: [1] Beilstein Journal of Organic Chemistry, 2012, vol. 8, p. 744 - 748
[2] Molecular Crystals and Liquid Crystals (1969-1991), 1991, vol. 204, p. 43 - 64
[3] Synthesis, 2009, # 8, p. 1305 - 1308
[4] Patent: WO2014/202580, 2014, A1,
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  • [ 351-28-0 ]
  • [ 656-65-5 ]
Reference: [1] Molecular Crystals and Liquid Crystals (1969-1991), 1991, vol. 204, p. 43 - 64
[2] Journal of the Chemical Society, 1958, p. 2815,2818
[3] Patent: WO2014/202580, 2014, A1,
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Reference: [1] Synthesis, 2009, # 8, p. 1305 - 1308
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  • [ 121219-03-2 ]
Reference: [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 9, p. 4189 - 4204
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  • [ 136434-77-0 ]
Reference: [1] Molecular Crystals and Liquid Crystals (1969-1991), 1991, vol. 204, p. 43 - 64
  • 8
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  • [ 444335-16-4 ]
Reference: [1] Patent: EP2692727, 2014, A2,
[2] Patent: US2014/179691, 2014, A1,
[3] Patent: WO2015/66413, 2015, A1,
[4] Patent: US9133213, 2015, B2,
[5] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5310 - 5321
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  • [ 153505-37-4 ]
Reference: [1] Patent: WO2012/83170, 2012, A1,
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  • [ 153505-36-3 ]
Reference: [1] Patent: WO2012/83170, 2012, A1,
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  • [ 73183-34-3 ]
  • [ 819057-45-9 ]
Reference: [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 8, p. 3923 - 3933
[2] Patent: WO2015/161014, 2015, A1, . Location in patent: Page/Page column 66-67
[3] Patent: WO2015/161011, 2015, A1, . Location in patent: Page/Page column 59
[4] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2513 - 2517
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  • [ 56-81-5 ]
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YieldReaction ConditionsOperation in experiment
85.8% With sulfuric acid; sodium 3-nitrobenzenesulfonate In water at 120 - 140℃; The starting material, 3-fluoro-4-bromoaniline (20 g, 0.105 mol) And catalyst sodium 3-nitrobenzenesulfonate (28 g, 0.124 mol, 1.2 eq) was added to a mixed solution of concentrated sulfuric acid (60 ml) and water (24 ml), heated to an internal temperature of 120 ° C, Glycerol (29 g, 0.315 mol, 3 eq) was added slowly and the reaction was warmed to 130-140 ° C overnight after the addition was complete and allowed to cool. The reaction solution was poured into crushed ice, concentrated ammonia to pH 8, extracted with dichloromethane, washed with water, After drying, column chromatography purified to give a yellow solid 20.3g, yield 85.8percent.
81% With sulfuric acid; sodium 3-nitrobenzenesulfonate In water at 110 - 140℃; 4-Bromo-3-fluoroaniline (D-1, 5.0 g, 26.3 mmol) and sodium 3-nitrobenzenesulfonate (7.1 g, 31.6 mmol)were added to the mixture of H2SO4 (20ml) and H2O (10ml). When the mixture was heated to 110C, Glycerin (7.27 g,78.9 mmol) was added slowly, then the reactionwas stirred at 140C overnight. After cooled to rt, the mixture was poured to alarge amount of ice water, concentrated ammonia water was added to adjust topH=8, then extracted with EtOAc, washed with brine and dried over anhydrous Na2SO4,then purified by flash column chromatography to afford6-bromo-7-fluoroquinoline as white solid (D-2,4.8 g, 81percent yield). LC-MS (ESI): [M+H]+=226. 1H NMR (400MHz, CDCl3) δ 8.93 (dd, J1=4.4Hz, J2=1.6 Hz, 1H),8.12-8.02 (m, 2H), 7.81 (d, J=9.6 Hz, 1H), 7.41 (dd, J1=8.4 Hz, J2=4.4 Hz, 1H).
51.9%
Stage #1: With sulfuric acid; iron(II) sulfate In nitrobenzene at 130℃; for 14 h;
Stage #2: With ammonia; water In nitrobenzene at 20℃;
Step 1: A mixture of compound A (90 g, 0.60 mol), glycerol (1800 g, 1.9 mol), ferrous sulfate (27 g, 0.0954 mol), nitrobenzene (99 mL, 0.95 mol) and concentrated sulfuric acid (261 mL, 4.77 mol) was heated at 130° C. for 14 h. The reaction mixture was allowed to cool to room temperature and basified to pH about 8 by 28percent NH3 solution. The resulting mixture was extracted with CH2Cl2 (1000 mL.x.3). The combined organic phases was evaporated and the residue was dried in vacuo to afford crude compound B, which was purified by column chromatography (silica gel, EtOAc/Petroleum ether=1:10) to yield compound B (56 g, 51.9percent) as a yellow solid.
44% at 140℃; for 12 h; Intermediate 2: (7-fluoroquinolin-6-yl)methanamine Step 1 : 6-Bromo-7-fluoroquinoline: To a mixture of 4-bromo-2-fluoroaniline (10 g, 52.62 mmol), ferrous sulphate (3.33 g, 11.97 mmol) and glycerol (15.78 ml) con. sulphuric acid (9.15 ml) was added slowly and the reaction mixture was heated to 140°C. After 12h, the reaction mixture was cooled to 0°C and the pH adjusted to 10-12 with 10percent sodium hydroxide solution. The reaction mixture was filtered through celite, washed with ethyl acetate and layers were separated. The organic layer was washed with brine solution, dried over sodium sulphate and concentrated. The crude product was purified by column chromatography with ethyl acetate: petroleum ether to afford the title compound as a white solid (4.9 g, 44percent). 'H- NMR (δ ppm, CDC13, 400 MHz): δ 8.96 (dd, J = 4.3, 2.7 Hz, 1H), 8.15 (m, 2H), 7.81 (d, J = 9.5 Hz, 1H), 7.42 (dd, J = 8.3,4.3 Hz, 1H).
44%
Stage #1: at 140℃; for 12 h;
Stage #2: With sodium hydroxide In water at 0℃;
Step 1:
6-Bromo-7-fluoroquinoline
To a mixture of 4-bromo-2-fluoroaniline (10 g, 52.62 mmol), ferrous sulphate (3.33 g, 11.97 mmol) and glycerol (15.78 ml) con. sulphuric acid (9.15 ml) was added slowly and the reaction mixture was heated to 140° C.
After 12 h, the reaction mixture was cooled to 0° C. and the pH adjusted to 10-12 with 10percent sodium hydroxide solution.
The reaction mixture was filtered through celite, washed with ethyl acetate and layers were separated.
The organic layer was washed with brine solution, dried over sodium sulphate and concentrated.
The crude product was purified by column chromatography with ethyl acetate:
petroleum ether to afford the title compound as a white solid (4.9 g, 44percent).
1H-NMR (δ ppm, CDCl3, 400 MHz): δ 8.96 (dd, J=4.3, 2.7 Hz, 1H), 8.15 (m, 2H), 7.81 (d, J=9.5 Hz, 1H), 7.42 (dd, J=8.3, 4.3 Hz, 1H).
42.5% With iron(III) sulfate; sulfuric acid In nitrobenzene for 7 h; Heating / reflux Intermediate 2: 6-Bromo-7-fluoro-quinoline; [0302] A mixture of 4-bromo-3-fluoroaniline (2.85 g, 15 mmol), ferric sulfate (0.95 g, 6.25 mmol), glycerol (5.66 g, 61 mmol), nitrobenzene (0.93 mL, 9.1 mmol), and concentrated sulfuric acid (2.61ml) was heated gently. After the first vigorous reaction, the mixture was boiled for 7h. Nitrobenzene was then evaporated in vacuo. The aqueous solution was acidified with glacial acetic acid, and a dark brown precipitate separated, which was collected and purified by flash chromatography (silica gel, petroleum/ethyl acetate= 8/1) to give 1.44 g of 6-bromo-7-fluoro-quinoline as white crystals (42.5percent yield).
42.5% With sulfuric acid; iron(II) sulfate In nitrobenzene for 7 h; Heating / reflux A mixture of 4-bromo-3-fluoro-phenylamine (2.85 g, 15 m mole), ferrous sulfate (0.95 g), glycerol (5.658 g, 4.5 ml), nitrobenzene (1.125 g, 0.93 ml) and concentrated sulfuric acid (2.61 mL) were heated gently. After the first vigorous reaction, the mixture was heated to reflux for 7 hours. Nitrobenzene was evaporated in vacuo. The aqueous solution was acidified with glacial acetic acid and dark brown precipitate separated, which was purified by flash chromatography (silica gel, petroleum: ethyl acetate= 8:1) to return compound title as white crystals (1.44 g, 42.5percent).
39%
Stage #1: at 130℃; for 14 h;
Stage #2: With ammonium hydroxide In waterCooling with ice
Intermediate E and F 7-Fluoro-quinoline-6-carbaldehyde and 7-(7-Fluoro-quinolin-6-yl)-methylamine 6-bromo-7-fluoro quinoline (i) To a suspension of 4-bromo-3-fluoro-phenylamine (100 g, 526 mmol) in concentrated sulfuric acid (290 ml.) was added glycerol (220 g, 2.39 mol, 4.5 eq.) followed by ferrous sulfate (30 g, 0.2 eq.). The reaction mixture was heated at 130 0C for 14 h, cooled to rt and poured into ice-water. The solution was neutralized with saturated aqueous ammonium hydroxide to pH 8 and extracted with DCM (2 L x 3). The combined organic layers were washed with brine (1 L x 3), dried over sodium sulfate and concentrated under reduced pressure to afford the crude product as a brown solid, which was purified by column chromatography (Petroleum:Ethyl acetate=10:1 ) to give 6-bromo-7-fluoro quinoline as a white solid (45 g, 39percent). 1H-NMR (400MHz, DMSO-Cf6) δ ppm 8.86 (s, 1 H), 8.56 (m, 1 H), 8.45 (m, 1 H), 7.90 (d, 1 H), 7.71 (m, 1 H).

Reference: [1] Patent: CN105968115, 2016, A, . Location in patent: Paragraph 0560-0562
[2] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 18, p. 4281 - 4290
[3] Patent: US2007/265272, 2007, A1, . Location in patent: Page/Page column 31-32
[4] Patent: WO2013/144737, 2013, A2, . Location in patent: Paragraph 252
[5] Patent: US2015/57309, 2015, A1, . Location in patent: Paragraph 0509
[6] Patent: WO2008/51808, 2008, A2, . Location in patent: Page/Page column 79
[7] Patent: WO2008/144767, 2008, A1, . Location in patent: Page/Page column 107
[8] Patent: WO2011/18454, 2011, A1, . Location in patent: Page/Page column 57
[9] Patent: WO2011/20861, 2011, A1, . Location in patent: Page/Page column 61
[10] Patent: US2011/281865, 2011, A1, . Location in patent: Page/Page column 84
[11] European Journal of Medicinal Chemistry, 2017, vol. 134, p. 147 - 158
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Reference: [1] Patent: US2012/245178, 2012, A1, . Location in patent: Page/Page column 21
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Reference: [1] Patent: WO2008/51808, 2008, A2, . Location in patent: Page/Page column 79
[2] Patent: WO2008/144767, 2008, A1, . Location in patent: Page/Page column 121
[3] Patent: WO2011/79804, 2011, A1, . Location in patent: Page/Page column 36
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YieldReaction ConditionsOperation in experiment
90% With N-iodo-succinimide In acetic acid at 25℃; for 1.5 h; To a solution of 4-bromo-3-fluoro-aniline (40.0 g, 211.6 mmol) in acetic acid (520 mL) was slowly added N-iodo succinimide (57.14 g, 253.9 mmol) 25° C.
The mixture was stirred for 90 min.
The reaction mixture was poured into ice-water and filtered.
The remanence was dried in vacuo to give 4-bromo-5-fluoro-2-iodo-phenylamine as a brown solid (60 g, 90percent).
87% With N-iodo-succinimide; acetic acid In ethyl acetate at 20℃; for 1.5 h; N-iodosuccinimide (2.90 ml, 28.9 mmol) was added to a solution of 4-bromo-3-fluoroaniline (5.00 g, 26.3 mmol) in AcOH (52.6 ml).
The reaction was maintained at ambient temperature for 1.5 h, then diluted with 20 mL toluene and concentrated.
The residue was dissolved in EtOAc and washed with 2 N aqueous NaOH.
The organic phase was washed with brine, dried over sodium sulfate, filtered, and concentrated.
The residue was purified by chromatography on silica gel (40-g Ultra SNAP column, 25-g silica gel loading column, 2-10percent EtOAc/Heptane) to give 4-bromo-5-fluoro-2-iodoaniline (7.23 g, 22.89 mmol, 87percent yield).
1H NMR (400 MHz, CHLOROFORM-d) δ 7.74-7.78 (m, 1H), 6.53-6.57 (m, 1H).
m/z (ESI) 315.9 (M+H)+.
62.5% at 0℃; To a stirred solution of 4-bromo-3-fluoroaniline (2.7 g, 14.2 mm) dissolved in acetic acid (25 mL), NIS (3.8 g, 1 .2 eq) was added portion wise at 0 00. After completion of the reaction, the acetic acid was removed under vacuo, the residue was dissolved in water and extracted with ethyl acetate, and the combined organic layer was washedwith water and brine solution. The solvent was removed under vacuo. The product was purified by combi-flash to yield the title compound (1 .0 g, 62.5percent) brown solid. 1H NMR: (DMSO-d6, 300MHz) 6 7.74-7.77 (d, 1 H), 6.68-6.71 (d, 1 H), 5.68 (5, 2H).
Reference: [1] Patent: US2012/252853, 2012, A1, . Location in patent: Page/Page column 25
[2] Patent: US9212182, 2015, B2, . Location in patent: Page/Page column 222
[3] Patent: WO2014/202580, 2014, A1, . Location in patent: Page/Page column 98
[4] Patent: US2010/81643, 2010, A1, . Location in patent: Page/Page column 125
[5] Patent: WO2012/103806, 2012, A1, . Location in patent: Page/Page column 39
[6] Patent: US2015/183802, 2015, A1, . Location in patent: Paragraph 1006-1009
[7] Patent: WO2015/102929, 2015, A1, . Location in patent: Page/Page column 120
[8] Patent: WO2017/153952, 2017, A1, . Location in patent: Page/Page column 176
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  • [ 510729-01-8 ]
YieldReaction ConditionsOperation in experiment
100% With sodium hydrogencarbonate In acetone at 15 - 22℃; for 1.5 h; Sodium hydrogen carbonate (27.63 g, 0.329 mol, 1.25 eq) and a saturated solution of sodium hydrogen carbonate (333 ml) were added to a stirred solution of 4-bromo-3-fluoroaniline (50.0 g, 0.263 mol, 1 eq) in acetone (660 ml).
The resulting mixture was cooled to 15° C. and benzyl chloroformate (39 ml, 0.276 mol, 1.05 eq) was added gradually, taking care that the reaction temperature did not exceed 22° C.
The mixture was stirred over 90 mins at room temperature and the acetone was removed under vacuum.
The aqueous layer was then extracted with ethyl acetate (3*150 ml).
The combined organic layers were then washed with a saturated sodium chloride solution, and dried over MgSO4.
After filtration, the solvent was removed, and n-hexane added.
The mixture was stirred during 30 min at room temperature, the crystals were filtrated and washed with hexane to give the first crop of solid.
The filtrate was evaporated, and the solid mixed with heptane at 0° C. and stirred during 30 min.
The product was again filtered, to give the second crop of solid.
The two crops were then combined, to give the product (85.3 g, quantitative) as of solid.
100%
Stage #1: With sodium hydrogencarbonate In tetrahydrofuran at 0℃; for 0.0833333 h;
Stage #2: at 0℃; for 3 h;
General procedure: The desired aniline (1 mmol) was dissolved in THF (4 mL), then NaHCO3 (2 mmol) was added and the mixture was cooled to 0 °C.  After 5 min, benzyl chloroformate (0.17 mL, 1.2 mmol) was added drop wise and the mixture was continuously stirred at 0 °C for 3 hrs. The reaction mixture was then diluted with DDW (10 ml) followed by extraction with EtOAc (3× 25 mL). The combined organic layers were washed with brine then dried over Na2SO4, filtered and concentrated under vacuum.
94% With sodium hydrogencarbonate In water; acetone at 0 - 20℃; for 24 h; 4-bromo-3-fluoroaniline (2.5 g, 13.1 mmol, 1.0 equiv) was dissolved in acetone: water (2:1, 30 mL) and the solution was cooled to 0°C. NaHCO3 (2.20 g, 26.3 mmol, 2.0 equiv), CBZ-Cl (2.68 g, 15.8 mmol, 1.2 equiv) were added and the reaction mixture was stirred at room temperature for 24 hours. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate and concentrated to afford product 3.4.1a (4.0 g, 94 percent yield). LCMS (mlz): 322.1 [M-2]. 1H NMR (400 MHz, DMSO) 6 10.17(s, 1H), 7.65—7.51 (m, 2H), 7.48—7.32(m, 5H), 7.27—7.17(m, 1H), 5.17(s, 2H).
92% With sodium hydrogencarbonate In tetrahydrofuran at 20℃; for 2.16667 h; cooling with ice To a 12-L, three-neck, round-bottom flask equipped with an overhead stirrer, nitrogen inlet/outlet, addition funnel and thermocouple was charged 4-bromo-3- fluoroaniline (800.0 g, 4.21 mol, Matrix lot No. Q13H), THF (6.4 L, 8 vol), and solid sodium bicarbonate (530.5 g, 6.32 mol, 1.5 eq). The addition funnel was charged with benzyl chloroformate (861.9 g, 5.05 mol, 1.2 eq), which was added dropwise to the reactor over 70 minutes. The temperature of the reaction was maintained below 200C with an ice water bath. The batch was aged 1 hour at room temperature at which point HPLC analysis indicated that the reaction was complete. The reaction mixture was transferred to a 22-L flask and the mixture was diluted with water (6.4 L, 8 vol). The two-phase mixture was warmed to 50°C and held at temperature for 16 hours to quench the excess benzyl chloroformate. The mixture was transferred hot to a separatory funnel to remove the lower aqueous phase. A rag layer was observed which was taken with the aqueous layer. The THF layer was filtered through Whatman No.1 filter paper to remove some particulates, and the mixture was transferred back to a 22-L flask equipped for distillation. Heptane was added in portions and distilled to remove the THF. (Note that it is best to distill some of the THF out first before adding the first amount of heptane.) A total of 26.5 L of heptane was added, and the total distillate collected was 25 L. At this point, the pot temperature had reached 97.7°C and the distillate coming over contained 0.9percent THF by 1H NMR analysis. The mixture was cooled to room temperature and the thick white slurry was filtered. The filter cake was washed with heptane (4 L). The product was dried in a vacuum oven at 400C to give 1257.0 g of intermediate 5 (92percent yield). The HPLC assay was 98.3percent (AUC).
173 g With sodium hydroxide In dichloromethane at 20℃; for 1 h; 100 g (528 mmol) of 3-fluoro-4-bromoaniline was dissolved in 500 mL of dichloromethane, 800 mL of an aqueous 1N NaOH solution was added thereto, and 82 mL (580 mmol) of Cbz-Cl (benzyl chloroformate) was slowly added dropwise thereto while stirring the resulting solution. The resulting solution was stirred at room temperature for 1 hour to separate an organic layer therefrom. The organic layer was washed twice with water, dehydrated using anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain 173 g (528 mmol) of Compound XXIX as a white solid. [0159] 1H NMR (600 MHz, CDCl3) δ 7.40 (m, 7H), 6.93 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 6.71 (s, 1H), 5.20 (s, 2H)
173 g With sodium hydroxide In dichloromethane; water at 20℃; Preparation of Compound XXIX 100 g (528 mmol) of 3-fluoro-4-bromoaniline was dissolved in 500 mL of dichloromethane, 800 mL of an aqueous 1N NaOH solution was added thereto, and 82 mL (580 mmol) of Cbz-Cl (benzyl chloroformate) was slowly added dropwise thereto while stirring the resulting solution. The resulting solution was stirred at room temperature for 1 hour to separate an organic layer therefrom. The organic layer was washed twice with water, dehydrated using anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain 173 g (528 mmol) of Compound XXIX as a white solid. [0171] 1H NMR (600 MHz, CDCl3) δ 7.40 (m, 7H), 6.93 (dd, J1=9.0 Hz, JZ=2.4 Hz, 1H), 6.71 (s, 1H), 5.20 (s, 2H)

Reference: [1] Patent: US9133213, 2015, B2, . Location in patent: Page/Page column 28
[2] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5310 - 5321
[3] Patent: WO2015/66413, 2015, A1, . Location in patent: Page/Page column 141; 142
[4] Patent: WO2010/42887, 2010, A2, . Location in patent: Page/Page column 16-17
[5] Patent: EP2692727, 2014, A2, . Location in patent: Paragraph 0158-0159
[6] Patent: US2014/179691, 2014, A1, . Location in patent: Paragraph 0169-0171
[7] Patent: CN103360379, 2017, B, . Location in patent: Paragraph 0072-0073
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Chemical Structure| 112279-60-4

[ 112279-60-4 ]

4-Bromo-2,5-difluoroaniline

Similarity: 0.94

Chemical Structure| 203302-95-8

[ 203302-95-8 ]

4-Bromo-3,5-difluoroaniline

Similarity: 0.92

Chemical Structure| 452-92-6

[ 452-92-6 ]

5-Bromo-2,4-difluoroaniline

Similarity: 0.92

Chemical Structure| 134168-97-1

[ 134168-97-1 ]

3-Bromo-5-fluoroaniline

Similarity: 0.91

Bromides

Chemical Structure| 656-64-4

[ 656-64-4 ]

3-Bromo-4-fluoroaniline

Similarity: 0.98

Chemical Structure| 112279-60-4

[ 112279-60-4 ]

4-Bromo-2,5-difluoroaniline

Similarity: 0.94

Chemical Structure| 203302-95-8

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4-Bromo-3,5-difluoroaniline

Similarity: 0.92

Chemical Structure| 452-92-6

[ 452-92-6 ]

5-Bromo-2,4-difluoroaniline

Similarity: 0.92

Chemical Structure| 134168-97-1

[ 134168-97-1 ]

3-Bromo-5-fluoroaniline

Similarity: 0.91

Amines

Chemical Structure| 656-64-4

[ 656-64-4 ]

3-Bromo-4-fluoroaniline

Similarity: 0.98

Chemical Structure| 112279-60-4

[ 112279-60-4 ]

4-Bromo-2,5-difluoroaniline

Similarity: 0.94

Chemical Structure| 203302-95-8

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4-Bromo-3,5-difluoroaniline

Similarity: 0.92

Chemical Structure| 452-92-6

[ 452-92-6 ]

5-Bromo-2,4-difluoroaniline

Similarity: 0.92

Chemical Structure| 134168-97-1

[ 134168-97-1 ]

3-Bromo-5-fluoroaniline

Similarity: 0.91