Name: 1370025-54-9|2-Bromo-6-fluoro-4-methylbenzaldehyde|98%
Brand: Ambeed
SKU: A568089
Rating: 94 (30 reviews)

1
[ 50-00-0 ]
[ 18349-09-2 ]
[ 1370025-54-9 ]

Yield	Reaction Conditions	Operation in experiment
38%	Stage #1: 2-bromo-6-fluoro-4-methyl aniline With hydrogenchloride; sodium acetate; copper(II) sulfate; sodium sulfite; sodium nitrite In water at 0℃; Stage #2: formaldehyd With hydroxylamine hydrochloride; sodium acetate In water Stage #3: With hydrogenchloride In water Reflux;

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

2
[ 1370025-54-9 ]
C₁₀H₁₀BrFO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium hexamethylsilazane / toluene 2: hydrogenchloride / water; acetone / Reflux 3: periodic acid; pyridinium chlorochromate / acetonitrile 4: hydrogenchloride / water / Reflux

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

3
[ 1370025-54-9 ]
C₁₁H₁₁Br₂FO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: potassium hexamethylsilazane / toluene 2: hydrogenchloride / water; acetone / Reflux 3: periodic acid; pyridinium chlorochromate / acetonitrile 4: hydrogenchloride / water / Reflux 5: lithium diisopropyl amide / tetrahydrofuran / -78 - -40 °C 6: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / Reflux

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

4
[ 1370025-54-9 ]
C₉H₈BrFO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium hexamethylsilazane / toluene 2: hydrogenchloride / water; acetone / Reflux

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

5
[ 1370025-54-9 ]
[ 1377934-85-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium hexamethylsilazane / toluene 2: hydrogenchloride / water; acetone / Reflux 3: periodic acid; pyridinium chlorochromate / acetonitrile

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

6
[ 1370025-54-9 ]
[ 1377934-87-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: potassium hexamethylsilazane / toluene 2: hydrogenchloride / water; acetone / Reflux 3: periodic acid; pyridinium chlorochromate / acetonitrile 4: hydrogenchloride / water / Reflux 5: lithium diisopropyl amide / tetrahydrofuran / -78 - -40 °C

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

7
[ 1370025-54-9 ]
[ 1377934-89-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: potassium hexamethylsilazane / toluene 2.1: hydrogenchloride / water; acetone / Reflux 3.1: periodic acid; pyridinium chlorochromate / acetonitrile 4.1: hydrogenchloride / water / Reflux 5.1: lithium diisopropyl amide / tetrahydrofuran / -78 - -40 °C 6.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / Reflux 7.1: potassium carbonate / acetone / 0.25 h / 20 °C 7.2: 12 h / Reflux

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

8
[ 1370025-54-9 ]
[ 1377934-90-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: potassium hexamethylsilazane / toluene 2.1: hydrogenchloride / water; acetone / Reflux 3.1: periodic acid; pyridinium chlorochromate / acetonitrile 4.1: hydrogenchloride / water / Reflux 5.1: lithium diisopropyl amide / tetrahydrofuran / -78 - -40 °C 6.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / Reflux 7.1: potassium carbonate / acetone / 0.25 h / 20 °C 7.2: 12 h / Reflux 8.1: hydrogenchloride; water; acetic acid / Reflux

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

9
[ 1370025-54-9 ]
[ 1377934-91-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1.1: potassium hexamethylsilazane / toluene 2.1: hydrogenchloride / water; acetone / Reflux 3.1: periodic acid; pyridinium chlorochromate / acetonitrile 4.1: hydrogenchloride / water / Reflux 5.1: lithium diisopropyl amide / tetrahydrofuran / -78 - -40 °C 6.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / Reflux 7.1: potassium carbonate / acetone / 0.25 h / 20 °C 7.2: 12 h / Reflux 8.1: hydrogenchloride; water; acetic acid / Reflux 9.1: dmap / 1,2-dichloro-ethane 10.1: trans-bromo(N-succinimidyl)-bis(triphenylphosphine)palladium(II); sodium carbonate / tetrahydrofuran; water / 3 h / Reflux 11.1: water; potassium hydroxide / ethanol / Reflux

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

10
[ 1370025-54-9 ]
C₁₆H₁₈BrFO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: potassium hexamethylsilazane / toluene 2.1: hydrogenchloride / water; acetone / Reflux 3.1: periodic acid; pyridinium chlorochromate / acetonitrile 4.1: hydrogenchloride / water / Reflux 5.1: lithium diisopropyl amide / tetrahydrofuran / -78 - -40 °C 6.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / Reflux 7.1: potassium carbonate / acetone / 0.25 h / 20 °C 7.2: 12 h / Reflux 8.1: hydrogenchloride; water; acetic acid / Reflux 9.1: dmap / 1,2-dichloro-ethane

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

11
[ 1370025-54-9 ]
C₂₂H₂₃FO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: potassium hexamethylsilazane / toluene 2.1: hydrogenchloride / water; acetone / Reflux 3.1: periodic acid; pyridinium chlorochromate / acetonitrile 4.1: hydrogenchloride / water / Reflux 5.1: lithium diisopropyl amide / tetrahydrofuran / -78 - -40 °C 6.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / Reflux 7.1: potassium carbonate / acetone / 0.25 h / 20 °C 7.2: 12 h / Reflux 8.1: hydrogenchloride; water; acetic acid / Reflux 9.1: dmap / 1,2-dichloro-ethane 10.1: trans-bromo(N-succinimidyl)-bis(triphenylphosphine)palladium(II); sodium carbonate / tetrahydrofuran; water / 3 h / Reflux

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

12
[ 1370025-54-9 ]
[ 4009-98-7 ]
C₁₀H₁₀BrFO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hexamethylsilazane In toluene

Reference： [1]Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru [Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5143 - 5150]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: In tetrahydrofuran for 1h; Inert atmosphere;	1 (1) Synthesis of compound 1a General procedure: Under nitrogen protection, m-bromofluorobenzene (1.000 g, 5.3 mmol) and 30 mL of anhydrous tetrahydrofuran (THF) were added to a dry 100 mL three-necked flask, Then the reaction flask was transferred to a low temperature reactor at -78°C, and after stirring for 30 minutes, 2.9 mL of lithium diisopropylamide (LDA, 2M in THF) was slowly added dropwise to the above reaction device, and after 30 minutes of reaction, 0.5 mL of anhydrous DMF was added dropwise to the above solution, and the reaction was continued for 1 h. After the reaction was completed, slowly drop 2 mL of saturated ammonium chloride solution into the above device to quench the reaction, then drop 5 mL of 0.5 mol/L HCl, and stir for another 15 minutes. After the reaction flask was removed from the low temperature reactor, 10 mL of 0.5 mol/L HCl was continued to be added, the solvent THF was removed by evaporation under reduced pressure, the residual mixture was extracted and separated with ethyl acetate (EA), and the collected organic phase was dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the concentrated filtrate was separated by column chromatography (petroleum ether) to obtain a white solid 1a.

14
[ 1370025-54-9 ]
4-bromo-6-methyl-1H-indazol-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium dodecyl-sulfate; [bis(acetoxy)iodo]benzene; ammonium acetate / water / 0.5 h / 70 °C 2: hydrazine hydrate / ethanol / 4 h / Reflux
	Multi-step reaction with 2 steps 1: sodium dodecyl-sulfate; [bis(acetoxy)iodo]benzene; ammonium acetate / water / 0.5 h / 70 °C 2: hydrazine hydrate / ethanol / 4 h / Reflux

Reference： [1]Current Patent Assignee: BAYER AG - US2015/126449, 2015, A1
[2]Current Patent Assignee: BAYER AG - WO2015/67549, 2015, A1

15
[ 1370025-54-9 ]
tert-butyl 4-(10-bromo-8-methyl-2-oxo-1,2-dihydropyrimido[1,2-b]indazol-4-yl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium dodecyl-sulfate; [bis(acetoxy)iodo]benzene; ammonium acetate / water / 0.5 h / 70 °C 2.1: hydrazine hydrate / ethanol / 4 h / Reflux 3.1: acetonitrile / 4 h / Reflux 3.2: 6 h / 70 °C
	Multi-step reaction with 3 steps 1.1: sodium dodecyl-sulfate; [bis(acetoxy)iodo]benzene; ammonium acetate / water / 0.5 h / 70 °C 2.1: hydrazine hydrate / ethanol / 4 h / Reflux 3.1: acetonitrile / 4 h / Reflux 3.2: 6 h / 70 °C

Reference： [1]Current Patent Assignee: BAYER AG - US2015/126449, 2015, A1
[2]Current Patent Assignee: BAYER AG - WO2015/67549, 2015, A1

16
[ 202865-83-6 ]
[ 68-12-2 ]
[ 1370025-54-9 ]

Yield	Reaction Conditions	Operation in experiment
95%		l-Bromo-3-fluoro-5-methylbenzene (5.00 g, 26.5 mmol) was dissolved in tetrahydrofuran (100 mL) and cooled to -78 C. Lithium diisopropyl amide (1.8 M in tetrahydrofuran, 16.2 mL, 29.1 mmol) was added. After stirring at -78 C for 30 min, N,N-dimethylformamide (2.32 g, 31.7 mmol) was added. After stirring at -78 C for an additional 15 min, acetic acid (6 mL) and water (100 mL) was added and the mixture was warmed to RT. After extraction with ethyl acetate, the organic phase was washed with 1 M hydrochloride acid solution and brine, and dried over magnesium sulfate. Concentration in vacuo afforded the title compound (5.45 g, 95% of theory). GC-MS (Method 1G): Rt = 4.39 min, MS (ESIPos): m/z = 217 [M+H]+
5.45 g		Example 148A 2-Bromo-6-fluoro-4-methylbenzaldehyde 1-Bromo-3-fluoro-5-methylbenzene (5.00 g, 26.5 mmol) was dissolved in tetrahydrofuran (100 mL) and cooled to -78 C. Lithium diisopropyl amide (1.8 M in tetrahydrofuran, 16.2 mL, 29.1 mmol) was added. After stirring at -78 C. for 30 min, N,N-dimethylformamide (2.32 g, 31.7 mmol) was added. After stirring at -78 C. for an additional 15 min, acetic acid (6 mL) and water (100 mL) was added and the mixture was warmed to RT. After extraction with ethyl acetate, the organic phase was washed with 1 M hydrochloride acid solution and brine, and dried over magnesium sulfate. Concentration in vacuo afforded the title compound (5.45 g, 95% of theory). GC-MS (Method 1G): Rt=4.39 min, MS (ESIPos): m/z=217 [M+H]+

Reference： [1]Patent: WO2015/67549,2015,A1 .Location in patent: Page/Page column 141
[2]Patent: US2015/126449,2015,A1 .Location in patent: Paragraph 0791 - 0793

17
[ 1370025-54-9 ]
[ 1023971-89-2 ]

Yield	Reaction Conditions	Operation in experiment
79%	With [bis(acetoxy)iodo]benzene; ammonium acetate; sodium dodecyl-sulfate; In water; at 70℃; for 0.5h;	A mixture of 2-bromo-6-fluoro-4-methylbenzaldehyde (5.45 g, 25.1 mmol), sodium lauryl sulfate (1.45 g, 5.03 mmol), (Diacetoxyiodo)benzene (12.1 g, 37.7 mmol) and ammonium acetate (9.68 g, 125.6 mmol) in water (25 mL) was stirred at 70 C for 30 min. After extraction with dichloromethane, the organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification via preparative HPLC (Method 1A) afforded the title compound (4.26 g, 79% of theory). GC-MS (Method 1G): Rt = 4.43 min, MS (ESIPos): m/z = 215 [M+H]+
4.26 g	With [bis(acetoxy)iodo]benzene; ammonium acetate; sodium dodecyl-sulfate; In water; at 70℃; for 0.5h;	Example 149A 2-Bromo-6-fluoro-4-methylbenzonitrile A mixture of 2-bromo-6-fluoro-4-methylbenzaldehyde (5.45 g, 25.1 mmol), sodium lauryl sulfate (1.45 g, 5.03 mmol), (Diacetoxyiodo)benzene (12.1 g, 37.7 mmol) and ammonium acetate (9.68 g, 125.6 mmol) in water (25 mL) was stirred at 70 C. for 30 min After extraction with dichloromethane, the organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification via preparative HPLC (Method 1A) afforded the title compound (4.26 g, 79% of theory). GC-MS (Method 1G): Rt=4.43 min, MS (ESIPos): m/z=215 [M+H]+

Reference： [1]Patent: WO2015/67549,2015,A1 .Location in patent: Page/Page column 142
[2]Patent: US2015/126449,2015,A1 .Location in patent: Paragraph 0794 - 0796

18
[ 1370025-54-9 ]
10-bromo-8-methyl-4-(piperidin-4-yl)pyrimido[1,2-b]indazol-2(1H)-one hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium dodecyl-sulfate; [bis(acetoxy)iodo]benzene; ammonium acetate / water / 0.5 h / 70 °C 2.1: hydrazine hydrate / ethanol / 4 h / Reflux 3.1: acetonitrile / 4 h / Reflux 3.2: 6 h / 70 °C 4.1: hydrogenchloride / 1,4-dioxane / 4 h / 20 °C

Reference： [1]Current Patent Assignee: BAYER AG - WO2015/67549, 2015, A1

19
[ 1370025-54-9 ]
[ 623-51-8 ]
ethyl 4-bromo-6-methylbenzo[b]thiophene-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h; Inert atmosphere;	31.4 Step 4) Synthesis of ethyl 4-bromo-6-methylbenzo[b]thiophene-2-carboxylate 2-Bromo-6-fluoro-4-methylbenzaldehyde (4.34 g, 20 mmol), potassium carbonate (5.53 g,40 mmol), ethyl 2-mercaptoacetate (2.88 g, 24 mmol) and N,N-dimethylformamide (40 mL) were added to a 100 mL single-neck flask. The resulting mixture was stirred at 80 °C for 12 h under nitrogen. The reaction mixture was cooled to room temperature and to the mixture was added saturated aqueous ammonium chloride (150 mL). The resulting mixture was extracted with ethyl acetate (100 mL x 2), and the organic layers were combined. The combined organic layers were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica-gel column chromatography (ethyl acetate/petroleum ether (v/v) = 1/100) to give the title compound as a white solid (5.09 g, 85%).‘H NIVIR (400 IVIFIz, CDC13) (ppm): 8.10 (s, 1H), 7.57 (s, 1H), 7.42 (s, 1H), 4.41 (q, J= 7.1 Hz, 2H), 2.46 (s, 3H), 1.42 (t, J= 7.1 Hz, 3H).

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 125

20
[ 18349-09-2 ]
[ 1370025-54-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: hydrogenchloride; sodium nitrite / water; acetonitrile / 1 h / 0 °C 1.2: 0 - 20 °C 2.1: tetrahydrofuran / 1 h / -45 °C 2.2: 20 °C