[ CAS No. 1211331-43-9 ]

Name: 1211331-43-9|3-Bromo-2,5-difluoropyridine|98%
Brand: Ambeed
SKU: A180037
Price: 18.0 USD
Availability: InStock
Rating: 93 (30 reviews)

{[proInfo.proName]} ,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 1211331-43-9

Structure of 1211331-43-9 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 100K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1211331-43-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1211331-43-9 ]

SDS

Alternatived Products of [ 1211331-43-9 ]

Product Details of [ 1211331-43-9 ]

CAS No. :	1211331-43-9	MDL No. :	MFCD12827553
Formula :	C₅H₂BrF₂N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	N/A
M.W :	193.98 g/mol	Pubchem ID :	-
Synonyms :

Safety of [ 1211331-43-9 ]

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 [ 1211331-43-9 ]

* 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.

Downstream synthetic route of [ 1211331-43-9 ]

[ 1211331-43-9 ] Synthesis Path-Downstream 1~40

1
[ 21717-96-4 ]
[ 1211331-43-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile / 20 °C 2: pyridine; sodium nitrite; hydrogen fluoride / 1.5 h / 0 - 50 °C / polyethylene reaction vessel

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

2
[ 869557-43-7 ]
[ 1211331-43-9 ]

Yield	Reaction Conditions	Operation in experiment
68%		NaN02 (1.4 g, 14.4 mmol) was added in portions to a solution of 3-bromo-5- fluoro-pyridin-2-ylamine (5.2 g, 17.3 mmol) in a HF/pyridine mixture (40 mL) in a polyethylene reaction vessel. The resulting mixture was stirred at 0 C for 0.5 h, then heated to 50 C and stirred for 1 h. The reaction mixture was poured onto crushed ice, partially neutralized with Na2C03, and extracted with EtOAc. The organic phase was washed with brine, dried over Na2S04, filtered and concentrated to give the product (4.1 g, 68%) as a white solid.
42%		(8a) 3-Bromo-2,5-difluoropyridine Sodium nitrite (1.97 g, 28.6 mmol) was added in small portions to a solution of <strong>[869557-43-7]3-bromo-5-fluoropyridin-2-amine</strong> (WO20062578 A1, 3.64 g, 19.1 mmol) in hydrofluoric acid pyridine (10 mL) at -10C. After stirring at room temperature for two hours, water (100 mL) and sodium bicarbonate were added to the reaction mixture at 0C, followed by extraction with ethyl acetate (100 mL). Then, the organic layer was washed with water (100 mL) twice and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (methylene chloride) to obtain the title compound (1.56 g, 42%) as a brown liquid. 1H-NMR (400 MHz, CDCl3): delta ppm: 7.78 (1H, dt, J = 2.7, 6.7 Hz), 8.02 (1H, dd, J = 1.6, 2.4 Hz).
42%	With pyridine hydrogenfluoride; sodium nitrite; at -10 - 20℃; for 2h;	Sodium nitrite (1.97 g, 28.6 mmol) was added in small portions to a solution of <strong>[869557-43-7]3-bromo-5-fluoropyridin-2-amine</strong> (, 3.64 g, 19.1 mmol) in hydrogen fluoride-pyridine (10 mL) at -10C. After stirring at room temperature for two hours, water (100 mL) and sodium bicarbonate were added to the reaction mixture at 0C, followed by extraction with ethyl acetate (100 mL). Then, the organic layer was washed with water (100 mL) twice and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (methylene chloride) to obtain the title compound (1.56 g, 42%) as a brown liquid. 1H-NMR (400 MHz, CDCl3): delta ppm: 7.78 (1H, dt, J = 2.7, 6.7 Hz), 8.02 (1H, dd, J = 1.6, 2.4 Hz).

	With pyridine hydrogenfluoride; sodium nitrite; at 10 - 20℃; for 2h;	To a mixture of <strong>[869557-43-7]3-bromo-5-fluoropyridin-2-amine</strong> (1.50 g, 7.85 mmol) and hydrogen fluoride pyridine (4 mL, 44 mmol), sodium nitrite (0.813 g, 11.8 mmol) was added at -10C in a several portions, and the mixture was stirred at room temperature for 2 hours. The mixture was diluted by addition of a saturated aqueous solution of sodium bicarbonate until it became basic, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of 3-bromo- 2, 5-difluoropyridine .
	With pyridine hydrofluoride; sodium nitrite; at -10 - 20℃; for 2h;	To a mixture of 3-bromo-5-fluoro-pyridin-2-amine(1.50 g, 7.85 mmol) and hydrogen fluoride pyridine (4 mL, 44 mmol), sodium nitrite was added at -10C in a several portions, and the mixture was stirred at room temperature for 2 hours. The mixture was diluted by addition of asaturated aqueous solution of sodium bicarbonate until it became basic, followed by extraction with ethyl acetate.The organic layer was washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of 3-bromo-2,5-difluoro-pyridine (1.00 g) . To a solution of a crude product of 3-bromo-2,5-difluoro- pyridine (1.00 g) obtained in the above step in ethanol (20 mL), a 20% ethanol solution of sodium ethoxide (2.84 mL, 6.61 mmol) was added at room temperature, andthe mixture was stirred at 80C for 1 hour in an oil bath.The mixture was cooled, and concentrated under reducedpressure. The residue was purified in an automaticchromatography apparatus (n-hexane/ethyl acetate = 100/0- 90/10) to obtain the title compound (1.04 g, yield for2 steps: 66%)?H NNR spectrum (CDC13, 400MHz) oe: 8.02 (1H, d, J =2.3 Hz), 7.80 (1H, d, J= 2.3 Hz), 4.41 (2H, q, J=7.0 Hz), 1.43 (3H, t, J = 7.0 Hz)
	With pyridine hydrofluoride; sodium nitrite; at -10 - 60℃; for 1.5h;	3-Bromo-5-fluoro-pyridin-2-ylamine (2.17 g, 11.361 mmol) was taken in pyridine hydrogen fluoride (15 mL) and cooled at -10 C. Sodium nitrite (1.176 g, 17.042 mmol) was added portionwise over 30 minutes. The mixture was allowed to come to room temperature and finally heated at 60 C. for 1 h. The mixture was poured onto crushed ice (ca 50 g). The mixture was neutralized with 1M Na2CO3 and organics extracted with EA (2*100 mL). The organic layers were further washed with brine, dried over MgSO4, filtered and concentrated to the crude 3-bromo-2,5-difluoro-pyridine as a brownish oil (1.48 g, 66%).

Reference： [1]Patent: WO2011/143366,2011,A1 .Location in patent: Page/Page column 75
[2]Patent: EP2404918,2012,A1 .Location in patent: Page/Page column 26
[3]Patent: EP2615081,2013,A1 .Location in patent: Paragraph 0188
[4]Patent: WO2018/119449,2018,A1 .Location in patent: Page/Page column 148-149
[5]Patent: WO2018/119444,2018,A1 .Location in patent: Page/Page column 148; 149
[6]Patent: US2019/381019,2019,A1 .Location in patent: Paragraph 0689-0691

3
[ 1211331-43-9 ]
[ 287944-16-5 ]
[ 1349185-09-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In 1,4-dioxane; water Reflux; Inert atmosphere;	4.3 To a solution of 3-bromo-2, 5-dif uoro-pyridine (4.1 g, 20.8 mmol) in dioxane (60 mL) was treated with Na2C03 (4.4 g, 41.6 mmol) in 20 mL of H20 as a solution, followed by additional of 4-(4,4,5,5-Tetramethyl-[l,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (4.8 g 22.9 mmol) and Pd(dppf)Cl2 (761 mg). The resulting mixture was heated at refluxing overnight under N2 atmosphere. TLC showed that most of the staring materials were consumed. The solution was filtered and the filtrate was concentrated to get a residue, which was purified by silica gel chromatography to give the product (3.7 g).

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1 Location in patent: Page/Page column 76

4
[ 1211331-43-9 ]
[ 1349184-83-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: caesium carbonate / dimethyl sulfoxide / 80 °C 2: potassium phosphate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 110 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

5
[ 1211331-43-9 ]
[ 1349184-84-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: caesium carbonate / dimethyl sulfoxide / 80 °C 2: potassium phosphate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 110 °C / Inert atmosphere 3: hydrogen / palladium on activated charcoal / methanol / 30 °C / 2068.65 Torr

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

6
[ 1211331-43-9 ]
[ 1349184-85-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 80 °C 2: potassium phosphate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 110 °C / Inert atmosphere 3: hydrogen / palladium on activated charcoal / methanol / 30 °C / 2068.65 Torr 4: hydrogenchloride / methanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

7
[ 1211331-43-9 ]
[ 1349185-10-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / Reflux; Inert atmosphere 2: hydrogen / palladium on activated charcoal / methanol / 20 °C

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

8
[ 1211331-43-9 ]
[ 1349185-11-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / Reflux; Inert atmosphere 2.1: hydrogen / palladium on activated charcoal / methanol / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 20 °C 3.2: 3 h / 60 °C

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

9
[ 1211331-43-9 ]
[ 1349185-12-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / Reflux; Inert atmosphere 2.1: hydrogen / palladium on activated charcoal / methanol / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 20 °C 3.2: 3 h / 60 °C 4.1: lithium hydroxide / water; methanol / 1 h / 20 - 50 °C

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

10
[ 1211331-43-9 ]
[ 1349185-13-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / Reflux; Inert atmosphere 2.1: hydrogen / palladium on activated charcoal / methanol / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 20 °C 3.2: 3 h / 60 °C 4.1: lithium hydroxide / water; methanol / 1 h / 20 - 50 °C 5.1: triethylamine; HATU / N,N-dimethyl-formamide / 24 h / 20 °C

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

11
[ 1211331-43-9 ]
[ 1349185-14-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / Reflux; Inert atmosphere 2.1: hydrogen / palladium on activated charcoal / methanol / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 20 °C 3.2: 3 h / 60 °C 4.1: lithium hydroxide / water; methanol / 1 h / 20 - 50 °C 5.1: triethylamine; HATU / N,N-dimethyl-formamide / 24 h / 20 °C 6.1: n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -78 °C 6.2: 0.5 h / -78 °C 6.3: 20 °C

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

12
[ 1211331-43-9 ]
cis-(1H-benzoimidazol-2-yl)-{3-[5-fluoro-3-(tetrahydropyran-4-yl)-pyridin-2-yloxy]cyclobutyl}methanone [ No CAS ]
trans-(1H-benzoimidazol-2-yl)-{3-[5-fluoro-3-(tetrahydropyran-4-yl)pyridin-2-yloxy]cyclobutyl}methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / Reflux; Inert atmosphere 2.1: hydrogen / palladium on activated charcoal / methanol / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 20 °C 3.2: 3 h / 60 °C 4.1: lithium hydroxide / water; methanol / 1 h / 20 - 50 °C 5.1: triethylamine; HATU / N,N-dimethyl-formamide / 24 h / 20 °C 6.1: n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -78 °C 6.2: 0.5 h / -78 °C 6.3: 20 °C 7.1: hydrogenchloride / tetrahydrofuran / 7 h / 20 - 60 °C

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

13
[ 1211331-43-9 ]
cis-benzothiazol-2-yl-{3-[5-fluoro-3-(tetrahydropyran-4-yl)-pyridin-2-yl]cyclobutyl}amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / Reflux; Inert atmosphere 2.1: hydrogen / palladium on activated charcoal / methanol / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 3.2: 2 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

14
[ 1211331-43-9 ]
trans-benzothiazol-2-yl-{3-[5-fluoro-3-(tetrahydropyran-4-yl)pyridin-2-yl]cyclobutyl}amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium carbonate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / Reflux; Inert atmosphere 2.1: hydrogen / palladium on activated charcoal / methanol / 20 °C 3.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 3.2: 2 h / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: INC LTD.; AMGEN INC - WO2011/143366, 2011, A1

15
[ 389890-43-1 ]
[ 1211331-43-9 ]
[ 1349184-78-6 ]

Yield	Reaction Conditions	Operation in experiment
41%	With caesium carbonate; In dimethyl sulfoxide; at 80℃;	To a mixture of 3-bromo-2,5-difluoro-pyridine (500 mg, 2.58 mmol ) and tert- butyl ((l S,3S)-3-hydroxycyclobutyl)carbamate (see PREPARATION 4A; 485 mg, 2.58 mmol) in DMSO (20 mL) was added CS2CO3 (1.68 g, 5.16 mmol), and then the mixture was stirred at 80C overnight. The reaction mixture was diluted with water and extracted with EtOAc (3 x 50 mL), washed with brine and dried over Na2S04. The dried organic layers were concentrated to tert-butyl ((l S,3S)-3-((3-bromo-5-fluoropyridin-2-yl)oxy)cyclobutyl)carbamate (380 mg, 1.06 mmol, 41%). ESI-MS (M+l): 361 calc. for Ci4H18BrFN203 360.

Reference： [1]Patent: WO2011/143366,2011,A1 .Location in patent: Page/Page column 58

16
[ 1211331-43-9 ]
2-ethoxy-5-fluoropyridine-3-sulfonyl chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ethanol / 97 h / 20 - 80 °C 2: N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 100 °C / Inert atmosphere 3: 1,3-dichloro-5,5-dimethylhydantoin; acetic acid / acetonitrile; water / 3 h / Cooling with ice
	Multi-step reaction with 3 steps 1: ethanol / 1 h / 20 - 80 °C 2: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 20 - 100 °C / Inert atmosphere 3: 1,3-dichloro-5,5-dimethylhydantoin; acetic acid / water; acetonitrile / 3 h / 20 °C / Cooling with ice

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE - WO2018/119449, 2018, A1
[2]Current Patent Assignee: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; DAIICHI SANKYO COMPANY, LIMITED - WO2018/119444, 2018, A1

17
[ 1211331-43-9 ]
3-(benzylsulfanyl)-2-ethoxy-5-fluoropyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ethanol / 97 h / 20 - 80 °C 2: N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: ethanol / 1 h / 20 - 80 °C 2: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 20 - 100 °C / Inert atmosphere

18
[ 1211331-43-9 ]
2-methoxyethyl (3R)-7-[(2-ethoxy-5-fluoropyridin-3-yl)sulfonyl]amino}-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: ethanol / 97 h / 20 - 80 °C 2.1: N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 100 °C / Inert atmosphere 3.1: 1,3-dichloro-5,5-dimethylhydantoin; acetic acid / acetonitrile; water / 3 h / Cooling with ice 4.1: hydrogenchloride / 1,4-dioxane; methanol / 0.83 h / 20 °C 4.2: 0.67 h / 80 °C

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE - WO2018/119449, 2018, A1

19
[ 1211331-43-9 ]
potassium [(2-ethoxy-5-fluoropyridin-3-yl)sulfonyl]{(3R)-4-[(2-methoxyethoxy)carbonyl]-3-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-7-yl}azanide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: ethanol / 97 h / 20 - 80 °C 2.1: N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 100 °C / Inert atmosphere 3.1: 1,3-dichloro-5,5-dimethylhydantoin; acetic acid / acetonitrile; water / 3 h / Cooling with ice 4.1: hydrogenchloride / 1,4-dioxane; methanol / 0.83 h / 20 °C 4.2: 0.67 h / 80 °C 5.1: potassium hydroxide / ethanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE - WO2018/119449, 2018, A1

20
[ 1211331-43-9 ]
[ 141-52-6 ]
3-bromo-2-ethoxy-5-fluoropyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
811 mg	In ethanol at 20 - 80℃; for 97h;	38.38a (38a) 3-bromo-2-ethoxy-5-fluoropyridine To a solution of a crude product of 3-bromo-2 , 5-difluoropyridine obtained in the above step in ethanol (40 mL) , a 20% ethanol solution of sodium ethoxide (5.04 mL, 11.8 mmol) was added at room (1188) temperature, the mixture was stirred at the same (1189) temperature as above for 4 days, and subsequently stirred at 80°C for 1 hour in an oil bath. The mixture was cooled, and concentrated under reduced pressure. The residue was purified in an automatic chromatography apparatus (n-hexane/ethyl acetate = 100/0 - 90/10) to obtain the title compound (811 mg, yield for (1190) 2 steps : 47%) . NMR spectrum (CDCI3, 400MHz) δ: 7.95 (1H, d, J = (1191) 2.7 Hz), 7.63 (1H, dd, J = 7.0, 2.7 Hz), 4.39 (2H, q, J = (1192) 7.0 Hz), 1.42 (3H, t, J = 7.0 Hz) .
1.04 g	In ethanol at 20 - 80℃; for 1h;	14.14a (14a) 3-bromo-2-ethoxy-5-fluoropyridine To a mixture of 3-bromo-5-fluoro-pyridin-2-amine(1.50 g, 7.85 mmol) and hydrogen fluoride pyridine (4 mL, 44 mmol), sodium nitrite was added at -10°C in a several portions, and the mixture was stirred at room temperature for 2 hours. The mixture was diluted by addition of asaturated aqueous solution of sodium bicarbonate until it became basic, followed by extraction with ethyl acetate.The organic layer was washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure to obtain a crude product of 3-bromo-2,5-difluoro-pyridine (1.00 g) . To a solution of a crude product of 3-bromo-2,5-difluoro- pyridine (1.00 g) obtained in the above step in ethanol (20 mL), a 20% ethanol solution of sodium ethoxide (2.84 mL, 6.61 mmol) was added at room temperature, andthe mixture was stirred at 80°C for 1 hour in an oil bath.The mixture was cooled, and concentrated under reducedpressure. The residue was purified in an automaticchromatography apparatus (n-hexane/ethyl acetate = 100/0- 90/10) to obtain the title compound (1.04 g, yield for2 steps: 66%)‘H NNR spectrum (CDC13, 400MHz) ö: 8.02 (1H, d, J =2.3 Hz), 7.80 (1H, d, J= 2.3 Hz), 4.41 (2H, q, J=7.0 Hz), 1.43 (3H, t, J = 7.0 Hz)

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE - WO2018/119449, 2018, A1 Location in patent: Page/Page column 148-149
[2]Current Patent Assignee: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; DAIICHI SANKYO COMPANY, LIMITED - WO2018/119444, 2018, A1 Location in patent: Page/Page column 148; 149

21
[ 1211331-43-9 ]
2-ethoxy-5-fluoro-N-[(5S)-5-methyl-5,6-dihydropyrazolo[1,5-d]pyrido[3,2-f][1,4]oxazepin-10-yl]pyridine-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: ethanol / 1 h / 20 - 80 °C 2.1: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 20 - 100 °C / Inert atmosphere 3.1: 1,3-dichloro-5,5-dimethylhydantoin; acetic acid / water; acetonitrile / 3 h / 20 °C / Cooling with ice 4.1: hydrogenchloride / methanol; 1,4-dioxane / 3 h / 20 °C 4.2: 0.5 h / 20 - 80 °C

Reference： [1]Current Patent Assignee: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; DAIICHI SANKYO COMPANY, LIMITED - WO2018/119444, 2018, A1

22
[ 1211331-43-9 ]
potassium [(2-ethoxy-5-fluoropyridin-3-yl)sulfonyl][(5S)-5-methyl-5,6-dihydropyrazolo[1,5-d]pyrido[3,2-f][1,4]oxazepin-10-yl]azanide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: ethanol / 1 h / 20 - 80 °C 2.1: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 20 - 100 °C / Inert atmosphere 3.1: 1,3-dichloro-5,5-dimethylhydantoin; acetic acid / water; acetonitrile / 3 h / 20 °C / Cooling with ice 4.1: hydrogenchloride / methanol; 1,4-dioxane / 3 h / 20 °C 4.2: 0.5 h / 20 - 80 °C 5.1: potassium hydroxide / ethanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; DAIICHI SANKYO COMPANY, LIMITED - WO2018/119444, 2018, A1

23
[ 1211331-43-9 ]
N-(5,6-dihydropyrazolo[1,5-d]pyrido[3,2-f][1,4]oxazepin-10-yl)-2-ethoxy-5-fluoropyridine-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: ethanol / 1 h / 20 - 80 °C 2.1: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 20 - 100 °C / Inert atmosphere 3.1: 1,3-dichloro-5,5-dimethylhydantoin; acetic acid / water; acetonitrile / 3 h / 20 °C / Cooling with ice 4.1: hydrogenchloride / methanol; 1,4-dioxane / 4 h / 20 °C 4.2: 2 h / 20 - 80 °C

Reference： [1]Current Patent Assignee: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; DAIICHI SANKYO COMPANY, LIMITED - WO2018/119444, 2018, A1

24
[ 1211331-43-9 ]
potassium 5,6-dihydropyrazolo[1,5-d]pyrido[3,2-f][1,4]oxazepin-10-yl[(2-ethoxy-5-fluoropyridin-3-yl)sulfonyl]azanide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: ethanol / 1 h / 20 - 80 °C 2.1: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1,4-dioxane / 4 h / 20 - 100 °C / Inert atmosphere 3.1: 1,3-dichloro-5,5-dimethylhydantoin; acetic acid / water; acetonitrile / 3 h / 20 °C / Cooling with ice 4.1: hydrogenchloride / methanol; 1,4-dioxane / 4 h / 20 °C 4.2: 2 h / 20 - 80 °C 5.1: potassium hydroxide / ethanol / 1 h / 20 °C

Reference： [1]Current Patent Assignee: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; DAIICHI SANKYO COMPANY, LIMITED - WO2018/119444, 2018, A1

25
[ 1211331-43-9 ]
[ 1242328-95-5 ]
[ 1242329-12-9 ]

Yield	Reaction Conditions	Operation in experiment
54%	With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 2h; Inert atmosphere;	67 4.8 General procedure for Copper-catalyzed coupling reaction to prepare 14 (General procedure G) General procedure: A solution of 13 (3.12g, 10.0mmol), 2-fluoro or 2-bromo substituted pyridine (11.0mmol), CuI (0.19g, 1.00mmol), 1,10-phenanthroline (0.18g, 1.00mmol) and Cs2CO3 (9.77g, 30mmol) in DMF (50mL) was stirred under N2 at 80°C for 2h. Aqueous NH4Cl solution (10%) was added to the cooled reaction mixture, and the mixture was extracted with EtOAc several times. The combined organic layers were washed with water and dried over anhydrous Na2SO4. After concentration under reduced pressure, the residue was purified by silica gel chromatography to obtain 14.

Reference： [1]Shinozuka, Tsuyoshi; Tsukada, Tomoharu; Fujii, Kunihiko; Tokumaru, Eri; Shimada, Kousei; Onishi, Yoshiyuki; Matsui, Yumi; Wakimoto, Satoko; Kuroha, Masanori; Ogata, Tsuneaki; Araki, Kazushi; Ohsumi, Jun; Sawamura, Ryoko; Watanabe, Nobuaki; Yamamoto, Hideki; Fujimoto, Kazunori; Tani, Yoshiro; Mori, Makoto; Tanaka, Jun [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 18, p. 5099 - 5117]

26
[ 1211331-43-9 ]
4-[(1R)-1-aminoethyl]cyclohexanol hydrochloride [ No CAS ]
4-[(1R)-1-[(3-bromo-5-fluoro-2-pyridyl)amino]ethyl]cyclohexanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62.96%	Stage #1: 4-[(1R)-1-aminoethyl]cyclohexanol hydrochloride With potassium carbonate In N,N-dimethyl-formamide at 15℃; for 0.5h; Stage #2: 3-bromo-2,5-difluoro-pyridine In N,N-dimethyl-formamide at 120℃; for 8h;	28.1 Step 1: 4-[(lR)-l-[(3-Bromo-5-fluoro-2-pyridyl)amino]ethyl]cyclohexanol To a solution of 4-[(lR)- l-aminoethyl]cyclohexanol hydrochloride (5.6 g, 30.9 mmol, 1.2 eq) in DMF (25 mL) was added K2CO3 (10.7 g, 77.3 mmol, 3 eq). The mixture was stirred at 15°C for 0.5h. 3-Bromo-2,5-difluoro-pyridine (5 g, 25.8 mmol, 1 eq) was added and the mixture was stirred at 120°C for 8h. LCMS detected desired compound. The reaction mixture was concentrated to dryness, H20 (lOOmL) was added, and extracted with ethyl acetate (180mL x 3). The combined organic layer was washed with brine (80mL), dried over Na2S04, filtered and concentrated. The residue was purified by flash silica gel chromatography (ISCO; 80 g SepaFlash Silica Flash Column, eluent of 0-45% ethyl acetate/Petroleum ether gradient 60 mL/min). 4-[(lR)- l-[(3-Bromo-5-fluoro-2- pyridyl)amino]ethyl]cyclohexanol (5.2 g, 16.23 mmol, 62.96% yield, 99% purity) was obtained as yellow oil. LCMS (M+H+) m/z: calcd 317.06; found 317.1.

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1 Location in patent: Page/Page column 78-79

27
[ 1211331-43-9 ]
1-((R)-1-(4-(3-cyclopropoxyazetidin-1-yl)cyclohexyl)ethyl)-5-fluoro-2-methyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 15 °C 1.2: 8 h / 120 °C 2.1: copper(l) iodide; potassium iodide; caesium carbonate; 2-Picolinic acid / N,N-dimethyl-formamide / 150 °C / Sealed tube; Microwave irradiation 3.1: Dess-Martin periodane / dichloromethane / 1.5 h / 15 °C 4.1: N-ethyl-N,N-diisopropylamine / methanol / 1 h / 15 °C 4.2: 1.5 h / 15 °C 4.3: 0.5 h / -70 °C 5.1: sodium hydroxide; water / 12 h / 80 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 30 °C 6.2: 12 h / 30 °C

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1

28
[ 1211331-43-9 ]
1-((R)-1-(4-(3-cyclopropoxyazetidin-1-yl)cyclohexyl)ethyl)-5-fluoro-2-methyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 15 °C 1.2: 8 h / 120 °C 2.1: copper(l) iodide; potassium iodide; caesium carbonate; 2-Picolinic acid / N,N-dimethyl-formamide / 150 °C / Sealed tube; Microwave irradiation 3.1: Dess-Martin periodane / dichloromethane / 1.5 h / 15 °C 4.1: N-ethyl-N,N-diisopropylamine / methanol / 1 h / 15 °C 4.2: 1.5 h / 15 °C 4.3: 0.5 h / -70 °C 5.1: sodium hydroxide; water / ethanol / 12 h / 80 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 30 °C 6.2: 12 h / 30 °C

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1

29
[ 1211331-43-9 ]
ethyl 5-fluoro-1-[(1R)-1-(4-hydroxycyclohexyl)ethyl]-2-methylpyrrolo[2,3-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 15 °C 1.2: 8 h / 120 °C 2.1: copper(l) iodide; potassium iodide; caesium carbonate; 2-Picolinic acid / N,N-dimethyl-formamide / 150 °C / Sealed tube; Microwave irradiation

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1

30
[ 1211331-43-9 ]
ethyl 5-fluoro-2-methyl-1-[(1R)-1-(4-oxocyclohexyl)ethyl]pyrrolo[2,3-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 15 °C 1.2: 8 h / 120 °C 2.1: copper(l) iodide; potassium iodide; caesium carbonate; 2-Picolinic acid / N,N-dimethyl-formamide / 150 °C / Sealed tube; Microwave irradiation 3.1: Dess-Martin periodane / dichloromethane / 1.5 h / 15 °C

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1

31
[ 1211331-43-9 ]
ethyl 1-[(1R)-1-[4-[3-(cyclopropoxy)azetidin-1-yl]cyclohexyl]ethyl]-5-fluoro-2-methylpyrrolo[2,3-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 15 °C 1.2: 8 h / 120 °C 2.1: copper(l) iodide; potassium iodide; caesium carbonate; 2-Picolinic acid / N,N-dimethyl-formamide / 150 °C / Sealed tube; Microwave irradiation 3.1: Dess-Martin periodane / dichloromethane / 1.5 h / 15 °C 4.1: N-ethyl-N,N-diisopropylamine / methanol / 1 h / 15 °C 4.2: 1.5 h / 15 °C 4.3: 0.5 h / -70 °C

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1

32
[ 1211331-43-9 ]
ethyl 1-[(1R)-1-[4-[3-(cyclopropoxy)azetidin-1-yl]cyclohexyl]ethyl]-5-fluoro-2-methylpyrrolo[2,3-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 15 °C 1.2: 8 h / 120 °C 2.1: copper(l) iodide; potassium iodide; caesium carbonate; 2-Picolinic acid / N,N-dimethyl-formamide / 150 °C / Sealed tube; Microwave irradiation 3.1: Dess-Martin periodane / dichloromethane / 1.5 h / 15 °C 4.1: N-ethyl-N,N-diisopropylamine / methanol / 1 h / 15 °C 4.2: 1.5 h / 15 °C 4.3: 0.5 h / -70 °C

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1

33
[ 1211331-43-9 ]
1-[(1R)-1-[4-[3-(cyclopropoxy)azetidin-1-yl]cyclohexyl]ethyl]-5-fluoro-2-methylpyrrolo[2,3-b]pyridine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 15 °C 1.2: 8 h / 120 °C 2.1: copper(l) iodide; potassium iodide; caesium carbonate; 2-Picolinic acid / N,N-dimethyl-formamide / 150 °C / Sealed tube; Microwave irradiation 3.1: Dess-Martin periodane / dichloromethane / 1.5 h / 15 °C 4.1: N-ethyl-N,N-diisopropylamine / methanol / 1 h / 15 °C 4.2: 1.5 h / 15 °C 4.3: 0.5 h / -70 °C 5.1: sodium hydroxide; water / 12 h / 80 °C

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1

34
[ 1211331-43-9 ]
1-[(1R)-1-[4-[3-(cyclopropoxy)azetidin-1-yl]cyclohexyl]ethyl]-5-fluoro-2-methylpyrrolo[2,3-b]pyridine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 15 °C 1.2: 8 h / 120 °C 2.1: copper(l) iodide; potassium iodide; caesium carbonate; 2-Picolinic acid / N,N-dimethyl-formamide / 150 °C / Sealed tube; Microwave irradiation 3.1: Dess-Martin periodane / dichloromethane / 1.5 h / 15 °C 4.1: N-ethyl-N,N-diisopropylamine / methanol / 1 h / 15 °C 4.2: 1.5 h / 15 °C 4.3: 0.5 h / -70 °C 5.1: sodium hydroxide; water / ethanol / 12 h / 80 °C

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2019/94552, 2019, A1

35
[ 1211331-43-9 ]
1-(3-bromo-5-fluoropyridin-2-yl)-N-(5-cyano-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: hydrazine hydrate / ethanol / 80 °C 2: triethylamine / ethanol / 80 °C 3: lithium hydroxide; water / tetrahydrofuran / 18 h / 20 °C 4: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 0.75 h / 20 °C / Reflux 5: triethylamine / tetrahydrofuran; dichloromethane / 20 °C

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2019/381019, 2019, A1

36
[ 1211331-43-9 ]
(3-bromo-5-fluoropyridin-2-yl)hydrazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.36 g	With hydrazine hydrate In ethanol at 80℃;	34.B B. (3-Bromo-5-fluoro-pyridin-2-yl)-hydrazine, cpd 34b Hydrazine monohydrate (1.95 mL, 25.518 mmol) was added to a solution of 3-bromo-2,5-difluoro-pyridine, cpd 34a (1.65 g, 8.506 mmol) in ethanol (15 mL) and stirred at 80° C. overnight. The mixture was then allowed to cool to room temperature and partially concentrated till the desired product crystallized. Water was added and suspension stirred for 30 minutes. The precipitate was filtered and washed with water. Air drying afforded the pure hydrazine (1.36 g, 72%). 1H NMR (300 MHz, DMSO-d6) δ 4.18 (s, 2H), 7.36 (s, 1H), 7.93 (dd, J=7.8, 2.5 Hz, 1H), 8.14 (d, J=2.6 Hz, 1H). MS m/z 206 (MH+).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2019/381019, 2019, A1 Location in patent: Paragraph 0689; 0692-0693

37
[ 1211331-43-9 ]
ethyl 1-(3-bromo-5-fluoropyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 80 °C 2: triethylamine / ethanol / 80 °C

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2019/381019, 2019, A1

38
[ 1211331-43-9 ]
1-(3-bromo-5-fluoropyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: hydrazine hydrate / ethanol / 80 °C 2: triethylamine / ethanol / 80 °C 3: lithium hydroxide; water / tetrahydrofuran / 18 h / 20 °C

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2019/381019, 2019, A1

39
[ 1211331-43-9 ]
C₁₀H₃BrClF₄N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: hydrazine hydrate / ethanol / 80 °C 2: triethylamine / ethanol / 80 °C 3: lithium hydroxide; water / tetrahydrofuran / 18 h / 20 °C 4: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 0.75 h / 20 °C / Reflux

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2019/381019, 2019, A1

40
[ 1211331-43-9 ]
1-(3-cyano-5-fluoropyridin-2-yl)-N-(5-cyano-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: hydrazine hydrate / ethanol / 80 °C 2: triethylamine / ethanol / 80 °C 3: lithium hydroxide; water / tetrahydrofuran / 18 h / 20 °C 4: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 0.75 h / 20 °C / Reflux 5: triethylamine / tetrahydrofuran; dichloromethane / 20 °C 6: copper(l) iodide / N,N-dimethyl-formamide / 1.5 h / 140 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US2019/381019, 2019, A1

Related Products

Historical Records

Related Functional Groups of
[ 1211331-43-9 ]

Fluorinated Building Blocks

[ 36178-05-9 ]

3-Bromo-2-fluoropyridine

Similarity: 0.87

[ 1349718-16-6 ]

4-Bromo-2,5-difluoropyridine

Similarity: 0.86

[ 1227502-60-4 ]

3-Bromo-2,4-difluoropyridine

Similarity: 0.82

[ 1260843-59-1 ]

3,4-Dibromo-5-fluoropyridine

Similarity: 0.81

[ 473596-07-5 ]

3,5-Dibromo-2-fluoropyridine

Similarity: 0.78

Bromides

[ 36178-05-9 ]

3-Bromo-2-fluoropyridine

Similarity: 0.87

[ 1349718-16-6 ]

4-Bromo-2,5-difluoropyridine

Similarity: 0.86

[ 1227502-60-4 ]

3-Bromo-2,4-difluoropyridine

Similarity: 0.82

[ 1260843-59-1 ]

3,4-Dibromo-5-fluoropyridine

Similarity: 0.81

[ 473596-07-5 ]

3,5-Dibromo-2-fluoropyridine

Similarity: 0.78

Related Parent Nucleus of
[ 1211331-43-9 ]

Pyridines

[ 36178-05-9 ]

3-Bromo-2-fluoropyridine

Similarity: 0.87

[ 1349718-16-6 ]

4-Bromo-2,5-difluoropyridine

Similarity: 0.86

[ 1227502-60-4 ]

3-Bromo-2,4-difluoropyridine

Similarity: 0.82

[ 1260843-59-1 ]

3,4-Dibromo-5-fluoropyridine

Similarity: 0.81

[ 473596-07-5 ]

3,5-Dibromo-2-fluoropyridine

Similarity: 0.78

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
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

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. 1211331-43-9 ]

Quality Control of [ 1211331-43-9 ]

Related Doc. of [ 1211331-43-9 ]

Product Details of [ 1211331-43-9 ]

Safety of [ 1211331-43-9 ]

Application In Synthesis of [ 1211331-43-9 ]

[ 1211331-43-9 ] Synthesis Path-Downstream 1~40

Related Functional Groups of [ 1211331-43-9 ]

Fluorinated Building Blocks

Bromides

Related Parent Nucleus of [ 1211331-43-9 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1211331-43-9 ]

Related Parent Nucleus of
[ 1211331-43-9 ]