[ CAS No. 839713-36-9 ] {[proInfo.proName]}

Name: 839713-36-9|1-(3-(4-Bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl)-3-(2,4-difluorophenyl)urea|97%
Brand: Ambeed
SKU: A101038
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Quality Control of [ 839713-36-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 839713-36-9 ]

CAS No. :	839713-36-9	MDL No. :	MFCD16619341
Formula :	C₁₈H₁₅BrF₂N₄O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	COSPVUFTLGQDQL-UHFFFAOYSA-N
M.W :	437.24	Pubchem ID :	11683556
Synonyms :	APD125

Safety of [ 839713-36-9 ]

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

Application In Synthesis of [ 839713-36-9 ]

* 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 [ 839713-36-9 ]
Downstream synthetic route of [ 839713-36-9 ]

[ 839713-36-9 ] Synthesis Path-Upstream 1~4

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Yield	Reaction Conditions	Operation in experiment
96.9%	at 12.9 - 19℃; for 4.91667 h;	Example 5; N-(2,4-Difluorophenyl)-N'-(4-methoxy-3-(4'-bromo-I '-methyl-lH-pyrazol-5'- yl) phenyl)urea (8); Both portions of 5-(2' -methoxy-5' -aminophenyl)-4-bromo-l-methyl-IH-pyrazole (2) from the previous example were combined by dissolution in toluene (15 L) at 27.6° C, suction filtration of the resulting solution, and rotary evaporation of the filtrate at <50° C and 10 mm HgA to a constant weight of 1127.0 g. A solution of 7 (1102.0 g of the 1127.0 g evaporation residue) in toluene (11.02 L) was stirred and refluxed at atmospheric pressure through a Dean-Stark trap under nitrogen. to remove 0.8 mL of water. After the condensate had become completely clear with no further accumulation of water in the Dean-Stark trap, the toluene solution was cooled under nitrogen to 12.9° C. To the resulting solution stirred under nitrogen was added 2,4- difluorophenyl isocyanate (617.9 g) by addition funnel over 40 minutes at a rate sufficiently slow to enable the reaction mixture to be maintained at 12.9-19° C with reactor jacket cooling. Solid started to precipitate in the reaction mixture about half way through the addition. After the addition had been completed, the reaction slurry continued to be stirred at 16° C under nitrogen. Conversion of 7 to 8 was 90percent, 91.2percent, and 92.6percent five, 60, and. 120 minutes, respectively, after the addition had been completed. Three hours after the addition had been completed, a second portion of 2,4-difluorophenyl isocyanate (24.4 g) was added, and, after continued stirring of the reaction mixture at 16° C under nitrogen for an additional 30 minutes, conversion of 7 to 8 was 94percent. One hour after the second addition, a third portion of 2,4-difluorophenyl isocyanate (9.7 g) was added, and, after continued stirring of the reaction mixture at 16° C under nitrogen for an additional 15 minutes, conversion of 7 to 8 was 95percent. The reaction mixture was then stirred at 20° C under nitrogen for an'additional 14.75 hours, after which conversion of 7 to 8 was 100percent. The reaction mixture was suction filtered, and the filtered solid was washed with 2.6° C toluene (2 x 1100 mL) and dried at 100° C and pressures falling to 1 mm HgA to provide 8 (1654.9 g, 96.9 percent yield) of 98.2 percent purity by HPLC with ca. 0.9 mole percent desbromo 8 as the largest impurity.

Reference： [1] Patent: WO2005/103011, 2005, A1, . Location in patent: Page/Page column 48

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Yield	Reaction Conditions	Operation in experiment
99.94%	at -5 - 70℃; for 11 h; Large scale	To a solution of 3-(4-bromo-2-methyl-2H-methyl-3-yl)-4-methoxy-phenylamine (16.7 kg) in acetonitrile (78.6 kg) in a 200 L-glass jacketed reactor with overhead stirring and nitrogen blanket at an internal temperature of <−10° C. 2,4-difluorophenyl-isocyanate (9.68 kg) was controlled charged through a 1 micron line filter at a rate substantially slow enough to prevent co-precipitation of the starting material in the product. After continued stirring at <−10° C. for approximately 1 hour post completion of the 2,4-difluorophenyl-isocyanate addition, the conversion of starting material to product was substantially complete. The product slurry was filtered and washed with cold acetonitrlie (26.3 kg) at <−5° C. producing the acetonitrile solvate of the product. Full house vacuum (30 in Hg ) was applied to the bottom outlet filter/dryer while nitrogen flowed through from the top enhancing the removal of volatile solvents without application of heat. Samples were removed from the bulk material and LOD was determined using an IR-200 Moisture Analyzer Instrument (Denver Instrument Company). The time course is shown below:
92.9%	at -10℃; for 1 h; Inert atmosphere	To a solution of 3-(4-bromo-2-methyl-2H-methyl-3-yl)-4-methoxy-phenylamme (16.7 kg) in acetonitπle (78.6 kg) m a 200 L glass jacketed reactor with overhead stirring and nitrogen blanket at an internal temperature of < -10 ⁰C 2,4-difluorophenyl-isocyanate (9.68 kg) was controlled charged through a 1 micron line filter at a rate substantially slow enough to prevent co-precipitation of the starting material in the product. After continued stirring at < -10 ⁰C for approximately 1 hour post completion of the 2,4-difluorophenyl-isocyanate addition, the conversion of starting material to product was substantially complete. The product slurry was filtered and washed with cold acetonitπle (26.3 kg) at < -5 ⁰C producing the acetomtπle solvate of the product. Full house vacuum (~30 in Hg ) was applied to the bottom outlet filter/dryer while nitrogen flowed through from the top enhancing the removal of volatile solvents without application of heat. Samples were removed from the bulk material and LOD was determined using an IR-200 Moisture Analyzer Instrument (Denver Instrument Company). The time course is shown below:Drying of the "wetcake" was maintained at ambient temperature under full house vacuum (-30 in Hg ) for about 19.5 h at which time the LOD was 7.28percent. At this point, the temperature was raised to 70 °C under full house vacuum (-30 in Hg ) for 11 hrs to afford l-[3-(4-bromo-2- methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea (24.2 kg, 99.94percent ΗPLC purity, form I determined by PXRD, and 92.9percent yield).

Reference： [1] Patent: US2016/67216, 2016, A1, . Location in patent: Paragraph 0834; 0835
[2] Patent: WO2010/62321, 2010, A1, . Location in patent: Page/Page column 75-76
[3] Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 1923 - 1936
[4] Patent: WO2006/81335, 2006, A2, . Location in patent: Page/Page column 34-37

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Reference： [1] Patent: WO2006/81335, 2006, A2, . Location in patent: Page/Page column 36-38

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Reference： [1] Patent: US2016/67216, 2016, A1,

[ 839713-36-9 ] Synthesis Path-Downstream 1~7

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1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(2,4-difluoro-phenyl)-urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%		<strong>[839713-36-9]1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea</strong> (Compound 8,1.44 g, 3.30 mmol) was dissolved in anhydrous CH2CI2 (30 ml). The solution was stirred while cooling the temperature to 0C in an ice water bath. After allowing it to stir for another 10 minutes, AlCl3 (1.76 g, 13.20 mmol) was added slowly. This was followed by stirring the reaction for an additional 20 minutes, and subsequently increasing the temperature to 80C. After one hour, the reaction was shown to be complete by TLC and LC/MS. It was worked up with EtOAc (2 x 50 ml) and 10% Potassium Sodium Tartrate (2 x 50 ml). Upon being treated to this work up, the aluminum was removed from the solution. The organic layer was then dried with Na2SO4, filtered, and the solvent was removed under reduced pressure. The residue was then purified by HPLC, yielding 1.43 g (100%) of Compound 103 LCMS m/z (%) = 425 (M+H81Br, 100), 423 (M+H79Br, 88). 1H NMR (400 MHz, DMSO-d6) delta 9.74 (s, 1H), 8.87 (s, 1H), 8.40 (s, 1H), 8.08-8.03 (m, 1H), 7.58 (s, 1H), 7.36 (dd, J1 = 8 Hz, J2 = 4 Hz, 1H), 7.33-7.27 (m, 1H), 7.28 (d, J= 2 Hz, 1H), 7.04-7.01 (m, 1H), 6.95 (d, J= 8 Hz, 1H), 3.67 (s, 3H).

Reference： [1]Patent: WO2005/12254,2005,A1 .Location in patent: Page/Page column 142-143

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C₁₈H₁₆F₂N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96.9%	In toluene; at 12.9 - 19℃; for 4.91667h;	Example 5; N-(2,4-Difluorophenyl)-N'-(4-methoxy-3-(4'-bromo-I '-methyl-lH-pyrazol-5'- yl) phenyl)urea (8); Both portions of 5-(2' -methoxy-5' -aminophenyl)-4-bromo-l-methyl-IH-pyrazole (2) from the previous example were combined by dissolution in toluene (15 L) at 27.6 C, suction filtration of the resulting solution, and rotary evaporation of the filtrate at <50 C and 10 mm HgA to a constant weight of 1127.0 g. A solution of 7 (1102.0 g of the 1127.0 g evaporation residue) in toluene (11.02 L) was stirred and refluxed at atmospheric pressure through a Dean-Stark trap under nitrogen. to remove 0.8 mL of water. After the condensate had become completely clear with no further accumulation of water in the Dean-Stark trap, the toluene solution was cooled under nitrogen to 12.9 C. To the resulting solution stirred under nitrogen was added 2,4- difluorophenyl isocyanate (617.9 g) by addition funnel over 40 minutes at a rate sufficiently slow to enable the reaction mixture to be maintained at 12.9-19 C with reactor jacket cooling. Solid started to precipitate in the reaction mixture about half way through the addition. After the addition had been completed, the reaction slurry continued to be stirred at 16 C under nitrogen. Conversion of 7 to 8 was 90%, 91.2%, and 92.6% five, 60, and. 120 minutes, respectively, after the addition had been completed. Three hours after the addition had been completed, a second portion of 2,4-difluorophenyl isocyanate (24.4 g) was added, and, after continued stirring of the reaction mixture at 16 C under nitrogen for an additional 30 minutes, conversion of 7 to 8 was 94%. One hour after the second addition, a third portion of 2,4-difluorophenyl isocyanate (9.7 g) was added, and, after continued stirring of the reaction mixture at 16 C under nitrogen for an additional 15 minutes, conversion of 7 to 8 was 95%. The reaction mixture was then stirred at 20 C under nitrogen for an'additional 14.75 hours, after which conversion of 7 to 8 was 100%. The reaction mixture was suction filtered, and the filtered solid was washed with 2.6 C toluene (2 x 1100 mL) and dried at 100 C and pressures falling to 1 mm HgA to provide 8 (1654.9 g, 96.9 % yield) of 98.2 % purity by HPLC with ca. 0.9 mole % desbromo 8 as the largest impurity.

Reference： [1]Patent: WO2005/103011,2005,A1 .Location in patent: Page/Page column 48

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Yield	Reaction Conditions	Operation in experiment
		To a mixture of N-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-acetamide (34.7 g, 0.1 mol) in methanol (347 mL) was added acetyl chloride (3 molar equivalents, 23 mL, 0.32 mol) at O0C and the solution was stirred at 450C for 24h. Formation of 3-(4-bromo-2-methyl- 2H-pyrazol-3-yl)-4-methoxy-phenylamine and consumption of N-[3-(4-bromo-2-methyl-2H- pyrazol-3-yl)-4-methoxy-phenyl]-acetamide were monitored by LCMS. The volatiles were removed, and the resulting residue was dissolved back in methanol (350 mL). Diisopropylethylamine (DIEA) (3 molar equivalents, 56.1 mL, 0.32 mol) was added at room temperature, and, after 0.5h isocyanate (1.1 molar equivalents, 12.73 mL, 0.101 mol) was then introduced at room temperature. Formation of l-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4- methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea and consumption of 3-(4-bromo-2-methyl-2H- pyrazol-3-yl)-4-methoxy-phenylamine were monitored by LCMS, and, after 3 hr, the mixture was heated to 8O0C and diluted using water (70 mL). The white solid product was filtered, washed using water (70 mL), and dried to provide l-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy- phenyl]-3-(2,4-difluoro-phenyl)-urea (32.46 g, 74.28 mmol, 69% yield). Example 5: Preparation of l-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3- (2,4-difluoro-phenyl)-urea from N- [4-methoxy-3-(2-methyl-2H-pyrazoI-3-yl)-phenyl] - acetaniide:To a mixture of N-[4-methoxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-acetamide (1 g, 4.08 mmol) in methanol (5 mL) was added NuBS (1.2 molar equivalent, 871 mg, 4.9 mmol) and the resulting mixture was stirred at room temperature for 2h. Formation of N-[3-(4-bromo-2- methyl-2H-pyrazol-3-yl)-4-methoxy-rhohenyl]-acetamide and consumption of N-[4-methoxy-3-(2- methyl-2H-pyrazol-3-yl)-phenyl]-acetamide were monitored by LCMS. The crude mixture was cooled to O0C, and acetyl chloride (6 molar equivalents, 1.32 mL, 24.28 mmol) was added. The resulting mixture was stirred at 450C for 24h while formation of 3-(4-bromo-2-methyl-2H- pyrazol-3-yl)-4-methoxy-phenylamine and consumption of N-[3-(4-bromo-2-methyl-2H-pyrazol- EPO <DP n="40"/>3-yl)-4-methoxy-phenyl]-acetamide were monitored by LCMS. The volatiles were removed, and the resulting residue was dissolved back in methanol (5mL). DIEA (3 molar equivalents, 2.13 mL, 12.24 mmol) was added at room temperature and after 0.5h, isocyanate (1.1 molar equivalents, 0.53 mL, 4.49 mmol) was then introduced at room temperature. Formation of l-[3- (4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea and consumption of 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine were monitored by LCMS, and, after 3 hr, the mixture was diluted using water (2mL). The white solid product was filtered, washed using water (10 mL), and dried to provide l-[3-(4-bromo-2-methyl-2H- pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea (1.55 g, 3.43 mmol, 84% yield).

Reference： [1]Patent: WO2006/81335,2006,A2 .Location in patent: Page/Page column 36-38

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Yield	Reaction Conditions	Operation in experiment
99.94%	In acetonitrile; at -5 - 70℃; for 11h;Large scale;	To a solution of 3-(4-bromo-2-methyl-2H-methyl-3-yl)-4-methoxy-phenylamine (16.7 kg) in acetonitrile (78.6 kg) in a 200 L-glass jacketed reactor with overhead stirring and nitrogen blanket at an internal temperature of <-10 C. 2,4-difluorophenyl-isocyanate (9.68 kg) was controlled charged through a 1 micron line filter at a rate substantially slow enough to prevent co-precipitation of the starting material in the product. After continued stirring at <-10 C. for approximately 1 hour post completion of the 2,4-difluorophenyl-isocyanate addition, the conversion of starting material to product was substantially complete. The product slurry was filtered and washed with cold acetonitrlie (26.3 kg) at <-5 C. producing the acetonitrile solvate of the product. Full house vacuum (30 in Hg ) was applied to the bottom outlet filter/dryer while nitrogen flowed through from the top enhancing the removal of volatile solvents without application of heat. Samples were removed from the bulk material and LOD was determined using an IR-200 Moisture Analyzer Instrument (Denver Instrument Company). The time course is shown below:
92.9%	In acetonitrile; at -10℃; for 1h;Inert atmosphere;	To a solution of 3-(4-bromo-2-methyl-2H-methyl-3-yl)-4-methoxy-phenylamme (16.7 kg) in acetonit?le (78.6 kg) m a 200 L glass jacketed reactor with overhead stirring and nitrogen blanket at an internal temperature of < -10 0C 2,4-difluorophenyl-isocyanate (9.68 kg) was controlled charged through a 1 micron line filter at a rate substantially slow enough to prevent co-precipitation of the starting material in the product. After continued stirring at < -10 0C for approximately 1 hour post completion of the 2,4-difluorophenyl-isocyanate addition, the conversion of starting material to product was substantially complete. The product slurry was filtered and washed with cold acetonit?le (26.3 kg) at < -5 0C producing the acetomt?le solvate of the product. Full house vacuum (~30 in Hg ) was applied to the bottom outlet filter/dryer while nitrogen flowed through from the top enhancing the removal of volatile solvents without application of heat. Samples were removed from the bulk material and LOD was determined using an IR-200 Moisture Analyzer Instrument (Denver Instrument Company). The time course is shown below:Drying of the "wetcake" was maintained at ambient temperature under full house vacuum (-30 in Hg ) for about 19.5 h at which time the LOD was 7.28%. At this point, the temperature was raised to 70 C under full house vacuum (-30 in Hg ) for 11 hrs to afford l-[3-(4-bromo-2- methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea (24.2 kg, 99.94% EtaPLC purity, form I determined by PXRD, and 92.9% yield).
	In propan-1-ol; at 0 - 80℃; for 0.25 - 3h;Product distribution / selectivity;	After a stirred mixture of methanol (90 mL), 50 wt % aqueous NaOH (61.60 g, ca. 40.4 mL, 0.7705 mole, 4.993 equivalents), andN-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy- phenyl]-acetamide (50.0 g, 0.1542 moles, 1.000 equivalent) had been heated under nitrogen with a 9O0C oil bath for 8.5 hr, the conversion of N-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4- methoxy-phenyl] -acetamide to 3 -(4-bromo-2-methyl-2H-pyrazol-3 -yl)-4-methoxy-phenylamine EPO <DP n="37"/>was found by HPLC to be 99.6%. Substantially all the methanol was then removed by distillation at reduced pressure. While maintaining the stirred residue at less than 5O0C, water (150 mL) and then cone, aqueous HCl (64 mL) were added to achieve a neutral pH of 7. Upon stirring at room temperature for 2 h, product 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine precipitated as a light tan solid, which was collected by suction filtration, washed with water (2 x 75 mL), air dried for two hours, and then dissolved in n-propanol (240 mL). 2,4- Difluorophenylisocyanate (19.5 g, 0.12572 mole, 0.815 equivalents) was added to the solution of crude 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine at a rate sufficiently slow to maintain the stirred reaction mixture at 40-500C with cooling. After the addition had been completed, stirring at that temperature was continued for 30 minutes, at which time conversion of 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine to l-[3-(4-bromo-2-methyl-2H- pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea was found by HPLC to be 98%. To improve stirrability, acetone (70 mL) and water (300 mL) were added. The resulting mixture was heated to 750C and then filtered. The filtered solid is washed with water and dried to provide l-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea.Example 2: Preparation of l-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3- (2,4-difluoro-phenyl)-urea fromiV-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy- phenyl]-acetamide (Telescoping by Extraction).A mixture of methanol (9 mL), 50 wt % aqueous NaOH (6.16g, 4.04 mL (at) d=1.525 g/mL, 77mmol, 5 equiv.) andN-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]- acetamide (5g, 15.4 mmol, 1 equiv.) was stirred under nitrogen and heated with a 9O0C oil-bath. LC/MS analysis revealed conversions of N-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy- phenyl]-acetamide to 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine of 86.4% after 3.5 h and 99.5% after an additional hour. After a total heating period of 5.5 h at 9O0C, methanol was distilled off the reaction mixture under reduced pressure, and the residue was diluted with water (20 mL). The aqueous mixture was then extracted with toluene three times (30 mL, 20 mL, and 15 mL). The toluene layers were combined and washed with water (4 X 15 mL) until the aqueous wash was neutral (pH 7). The toluene solution was filtered and concentrated under reduced pressure until about 12-15 mL toluene remained with the product [3-(4-bromo-2- methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine, theoretical yield of 4.35 g, 15.4 mmol]. After n-propanol (35 mL) was added to the crude 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy- EPO <DP n="38"/>phenylamine, 2,4-difluorophenyl isocyanate (2.62g, 2.00 mL, 16.9 mmol, 1.1 equiv.) was added dropwise while the stirred reaction mixture was maintained at 0-5C with cooling. The mixture was then allowed to warm to room temperature. After approximately 15 min., a solid started to precipitate. n-Propanol (10 mL) added to facilitate stirring, and the resulting mixture was filtered. The filtered white solid was washed with n-propanol (10 mL) and dried overnight at 6O0C at about 20 torr to provide l-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro- phenyl)-urea 4.25g (63%). HPLC purity, 99.05 (by peak area). IH NMR (Bruker 400 MHz, DMSO-^6) delta 9.01 (s, IH, NH), 8.45 (IH, NH), 8.05 (m, IH, ArH), 7.61 (s, IH, ArH), 7.53 (dd, IH, J = 3 Hz, 9 Hz, ArH), 7.36 (d, IH, J = 3 Hz, ArH), 7.30 (m, IH, ArH), 7.16 (d, IH, J=9 Hz), 7.08 (m, IH, ArH), 3.77 (s, 3 H), 3.63 (s, 3 H).Example 4: Preparation of l-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3- (2,4-difluoro-phenyl)-urea fromiV-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy- phenyl]-acetamide: EPO <DP n="39"/>To a mixture of N-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-acetamide (3 g, 9.25 mmol) in 1-propanol (3 mL)and water (6 mL) was added sulfuric acid (2 molar equivalents, 1.81 g, 18.51 mmol) at room temperature and the solution was stirred at 1020C for 5h. Formation of 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine and consumption of N-[3-(4-bromo-2-metriyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-acetamide were monitored by LCMS. Potassium carbonate (2.2 molar equivalents, 2.81 g, 20.36 mmol) was added, the resulting mixture was stirred for 0.5h, and the solid salts were removed by filtrati...

Reference： [1]Patent: US2016/67216,2016,A1 .Location in patent: Paragraph 0834; 0835
[2]Patent: WO2010/62321,2010,A1 .Location in patent: Page/Page column 75-76
[3]Journal of Medicinal Chemistry,2010,vol. 53,p. 1923 - 1936
[4]Patent: WO2006/81335,2006,A2 .Location in patent: Page/Page column 34-37

6
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[ 839713-36-9 ]

Reference： [1]Patent: US2016/67216,2016,A1

7
[ 839713-36-9 ]
1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-dimethylamino-ethoxy)-phenyl]-3-(2,4-difluoro-phenyl)-urea [ No CAS ]

Reference： [1]Patent: WO2005/12254,2005,A1

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Related Parent Nucleus of
[ 839713-36-9 ]

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Ghs Precautionary Statements

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 839713-36-9 ] {[proInfo.proName]}

Quality Control of [ 839713-36-9 ]

Related Doc. of [ 839713-36-9 ]

Product Details of [ 839713-36-9 ]

Safety of [ 839713-36-9 ]

Application In Synthesis of [ 839713-36-9 ]

[ 839713-36-9 ] Synthesis Path-Upstream 1~4

[ 839713-36-9 ] Synthesis Path-Downstream 1~7

Related Functional Groups of [ 839713-36-9 ]

Fluorinated Building Blocks

Aryls

Bromides

Ethers

Amides

Ureas

Amines

Related Parent Nucleus of [ 839713-36-9 ]

Pyrazoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 839713-36-9 ]

Related Parent Nucleus of
[ 839713-36-9 ]