1050501-88-6|2-Bromo-6-chloropyridin-3-amine| Ambeed

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Quality Control of [ 1050501-88-6 ] Purity: 97% SDS Specification

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Product Details of [ 1050501-88-6 ]

CAS No. :	1050501-88-6
Formula :	C₅H₄BrClN₂
M.W :	207.46
SMILES Code :	NC1=CC=C(Cl)N=C1Br
MDL No. :	MFCD11504927
InChI Key :	OPKKXWUGXHSFQI-UHFFFAOYSA-N
Pubchem ID :	45480430

Safety of [ 1050501-88-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 1050501-88-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	41.35
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	38.91 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.6
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.16
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.09
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.19
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.03
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.81

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.98
Solubility	0.217 mg/ml ; 0.00105 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.61
Solubility	0.51 mg/ml ; 0.00246 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.14
Solubility	0.15 mg/ml ; 0.000724 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.03 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.11

Application In Synthesis of [ 1050501-88-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 1050501-88-6 ]

[ 1050501-88-6 ] Synthesis Path-Downstream 1~35

1
[ 1050501-88-6 ]
[ 1352200-87-3 ]

References: [1]Patent: US2011/306589,2011,A1 .
[2]Patent: WO2011/154327,2011,A1 .

2
[ 1050501-88-6 ]
[ 1352200-88-4 ]

References: [1]Patent: US2011/306589,2011,A1 .
[2]Patent: WO2011/154327,2011,A1 .

3
[ 64-17-5 ]
[ 201230-82-2 ]
[ 1050501-88-6 ]
[ 1352200-86-2 ]

Yield	Reaction Conditions	Operation in experiment
30%	With triethylamine;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In toluene; at 80℃; under 37503.8 Torr; for 16h;Inert atmosphere; autoclave;	A solution of <strong>[1050501-88-6]2-bromo-6-chloro-pyridin-3-ylamine</strong> (1.0 g, 4.8 mmol) in ethanol (15 ml) and toluene (15 ml) was charged under argon atmosphere with (1,1'-bis(diphenylphosphino)-ferrocene)palladium(II) dichloride complex with dichloromethane (200 mg ; 0.245 mmol) and triethylamine (1.67 ml, 12.1 mmol) in an autoclave, was flushed with carbon monoxide (3 times, 20 bar) and stirred at 80 C. under carbon monoxide atmosphere (50 bar) for 16 h. Upon cooling to ambient temperature and pressure release, the reaction mixture was filtrated and the solvents were removed. The product was obtained after purification by silica gel chromatography using a dichloromethane /methanol /ammonia gradient and recrystallisation from dichloromethane as light yellow solid (290 mg, 30%).
30%	With triethylamine;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In toluene; at 80℃; under 15001.5 - 37503.8 Torr; for 16h;Inert atmosphere; autoclave;	A solution of <strong>[1050501-88-6]2-bromo-6-chloro-pyridin-3-ylamine</strong> (1.0 g, 4.8 mmol) in ethanol (15 ml) and toluene (15 ml) was charged under argon atmosphere with (l,l'-bis(diphenylphosphino)- ferrocene)palladium(II) dichloride complex with dichloromethane (200 mg; 0.245 mmol) and triethylamine (1.67 ml, 12.1 mmol) in an autoclave, was flushed with carbon monoxide (3 times, 20 bar) and stirred at 80 C under carbon monoxide atmosphere (50 bar) for 16 h. Upon cooling to ambient temperature and pressure release, the reaction mixture was filtrated and the solvents were removed. The product was obtained after purification by silica gel chromatography using a dichloromethane/methanol/ammonia gradient and recrystallisation from dichloromethane as light yellow solid (290 mg, 30%).

References: [1]Patent: US2011/306589,2011,A1 .Location in patent: Page/Page column 91-92.
[2]Patent: WO2011/154327,2011,A1 .Location in patent: Page/Page column 223.

4
[ 1050501-88-6 ]
[ 127-17-3 ]
[ 800401-63-2 ]

Yield	Reaction Conditions	Operation in experiment
82.6%	With palladium diacetate; triethylamine; In N,N-dimethyl-formamide; at 100℃;	Step 2: synthesis of 5-chloro-lH-pyrrolo[3,2-b]pyridine-2-carboxylic acid 11-b2-oxopropanoic acid (36.22 g, 411.31 mmol), palladium(II)acetate (7.74 g, 34.15 mmol) and Et3N (69.11 g, 682.94 mmol) were added to a solution of 2-bromo-6- chloropyridin-3 -amine 11-a (32.20 g, 155.21 mmol) and TPP (35.83 g, 136.59 mmol) in dry DMF (300 ml). The reaction mixture was stirred at 100C overnight. The solvent was then evaporated, water was added and the water layer was washed with EtOAc. The water layer was acidified with cone. HCl. The precipitate was filtered off and dried, yielding 25.21 g of the wanted product 11-b (82.6 %). m/z = 197.1 (M+H)+, CI pattern.
82.6%	With palladium diacetate; triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 100℃;	2-oxopropanoic acid (36.22 g, 411.31 mmol), palladium(II)acetate (7.74 g, 34.15 mmol) and Et3N (69.11 g, 682.94 mmol) were added to a solution of 2-bromo-6- chloropyridin-3-amine 28-b (32.20 g, 155.21 mmol) and TPP (35.83 g, 136.59 mmol) in dry DMF (300 ml). The reaction mixture was stirred at 100C overnight. The solvent was then evaporated, water was added and the water layer was washed with EtOAc. The water layer was acidified with cone. HC1. The precipitate was filtered off and dried, yielding 25.21 g of the intermediate 28-c (82.6 %)
82.6%	With palladium diacetate; triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 100℃;	2-oxopropanoic acid (36.22 g, 411.31 mmol), palladium(II)acetate (7.74 g,34.15 mmol) and Et3N (69.11 g, 682.94 mmol) were added to a solution of<strong>[1050501-88-6]2-bromo-6-chloropyridin-3-amine</strong> 49-a (32.20 g, 155.21 mmol) and TPP (35.83 g, 136.59 mmol)in dry DMF (300 ml). The reaction mixture was stirred at 100C overnight. The solvent was then evaporated, water was added and the water layer was washed withEtOAc. The water layer was acidified with cone. HCl. The precipitate was filtered offand dried, yielding 25.21 g of the wanted product 49-b (82.6 %).m/z = 197.1 (M+It.

82.6%	With palladium diacetate; triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 100℃;	Step 2: synthesis of 5-chloro-1H-pyrrolo[3,2-bjpyridine-2-carboxylic acid (intermediate 20b)2-oxopropanoic acid (36.22 g, 411.31 mmol), palladium(II)acetate (7.74 g, 34.15 mmol) and Et3N (69.11 g, 682.94 mmol) were added to a solution of 2-bromo-6- chloropyridin-3-amine 20a (32.20 g, 155.21 mmol) and TPP (35.83 g, 136.59 mmol) in dry DMF (300 ml). The reaction mixture was stirred at 100C overnight. The solvent was then evaporated, water was added and the water layer was washed with EtOAc.The water layer was acidified with conc. HC1. The precipitate was filtered off and dried, yielding 25.21 g of the wanted product 20b (82.6 %). m/z = 197.1 (M+H), Cl pattern.
82.6%	With palladium diacetate; triethylamine; triphenylphosphine; In water; N,N-dimethyl-formamide; at 100℃;	2-oxopropanoic acid (36.22 g, 411.31 mmol), palladium(II)acetate (7.74 g, 34.15 mmol) and Et3N (69.11 g, 682.94 mmol) were added to a solution of <strong>[1050501-88-6]2-bromo-6-chloropyridin-3-amine</strong> 49-a (32.20 g, 155.21 mmol) and TPP (35.83 g, 136.59 mmol) in dry DMF (300 ml). The reaction mixture was stirred at 100 C. overnight. The solvent was then evaporated, water was added and the water layer was washed with EtOAc. The water layer was acidified with conc. HCl. The precipitate was filtered off and dried, yielding 25.21 g of the wanted product 49-b (82.6%). m/z=197.1 (M+1)+.
	With palladium diacetate; triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 115℃; for 18h;Inert atmosphere;	To the mixture of <strong>[1050501-88-6]2-bromo-6-chloropyridin-3-amine</strong> (5 g, 24.4 mmol), Pd(OAc)2 (1.09 g, 4.88 mmol), PPh3 (1.91 g, 7.32 mmol) and triethylamine (10.8 g, 107.3 mmol) in DMF (30 mL) in N2 atmosphere, was added 2-oxopropanoic acid (5.69 g, 64.6 mmol) by a syringe. The resulting mixture was heated at 115C for l8hrs under N2. The reaction mixture was cooled to room temperature and poured into water (200 mL) The resulting precipitate was filtered and the filtrate was washed with EA(30 mL x 3). The pH of aqueous phase was adjusted with iN aq. HC1 solution to pH 4, and the resulting precipitate was collected by filtration and dried by reduced pressure to give 5-chloro-1H-pyrrolo[3,2-bjpyridine-2- carboxylic acid (2.44 g, 51%) as a solid. HPLC/UV purity: 90%; LC-MS (ESI): 197.1 (M + 1).

References: [1]Patent: WO2012/80450,2012,A1 .Location in patent: Page/Page column 26.
[2]Patent: WO2013/186335,2013,A1 .Location in patent: Page/Page column 87; 88.
[3]Patent: WO2013/186333,2013,A1 .Location in patent: Page/Page column 102; 103.
[4]Patent: WO2014/60411,2014,A1 .Location in patent: Page/Page column 56.
[5]Patent: US2015/111868,2015,A1 .Location in patent: Paragraph 0858; 0859.
[6]Patent: WO2018/204176,2018,A1 .Location in patent: Paragraph 00472.

5
[ 5350-93-6 ]
[ 1050501-88-6 ]

Yield	Reaction Conditions	Operation in experiment
99.8%		Step 1: synthesis of 2-bromo-6-chloropyridin-3-amine 11-aBromine (24.86 g, 155.57 mmol) was added to a solution of 6-chloropyridin-3 -amine (20.00 g, 155.57 mmol) and sodium acetate (25.52 g, 311.14 mmol) in acetic acid (383 ml). The reaction mixture was stirred at room temperature for 1 hour. Acetic acid was then evaporated. The residue was dissolved in EtOAc, washed with saturated aqueous Na2C03, water and brine. The organic layer was dried over MgS04, filtered and evaporated, yielding 32.20 g of the desired product 11-a (99.8%). m/z = 206.96 (M+H)+, Cl+Br pattern.
99.8%	With bromine; sodium acetate; acetic acid; at 20℃; for 1h;	Bromine (24.86 g, 155.57 mmol) was added to a solution of 6-chloropyridin-3 -amine 28-a (20.00 g, 155.57 mmol) and sodium acetate (25.52 g, 311.14 mmol) in acetic acid (383 ml). The reaction mixture was stirred at room temperature for 1 hour. Acetic acid was then evaporated. The residue was dissolved in EtOAc, washed with saturated aqueous Na2C03, water and brine. The organic layer was dried over MgSC^, filtered and evaporated, yielding 32.20 g of the desired intermediate 28-b (99.8%).
99.8%	With bromine; sodium acetate; acetic acid; at 20℃; for 1h;	Bromine (24.86 g, 155.57 mmol) was added to a solution of6-chloropyridin-3-amine (20.00 g, 155.57 mmol) and sodium acetate (25.52 g, 311.14 mmol) in acetic acid(383 ml). The reaction mixture was stirred at room temperature for 1 hour. Acetic acidwas then evaporated. The residue was dissolved in EtOAc, washed with saturatedaqueous Na2C03, water and brine. The organic layer was dried over MgS04, filteredand evaporated, yielding 32.20 g of the desired product 49-a (99.8%). m/z = 206.96 (M+ It

99.8%	With bromine; sodium acetate; acetic acid; at 25℃; for 1h;	Step 1: synthesis of 2-bromo-6-chloropyridin-3-amine (intermediate 20a)Bromine (24.86 g, 155.57 mmol) was added to a solution of 6-chloropyridin-3-amine(20.00 g, 155.57 mmol) and sodium acetate (25.52 g, 311.14 mmol) in acetic acid(383 ml). The reaction mixture was stirred at room temperature for 1 hour. Acetic acidwas then evaporated. The residue was dissolved in EtOAc, washed with saturatedaqueous Na2CO3, water and brine. The organic layer was dried over MgSO4, filteredand evaporated, yielding 32.20 g of the desired product 20a (99.8%). m/z = 206.96 (M+H), Cl+Br pattern.
99.8%	With bromine; sodium acetate; acetic acid; In ethyl acetate; at 20℃; for 1h;	Bromine (24.86 g, 155.57 mmol) was added to a solution of 6-chloropyridin-3-amine (20.00 g, 155.57 mmol) and sodium acetate (25.52 g, 311.14 mmol) in acetic acid (383 ml). The reaction mixture was stirred at room temperature for 1 hour. Acetic acid was then evaporated. The residue was dissolved in EtOAc, washed with saturated aqueous Na2CO3, water and brine. The organic layer was dried over MgSO4, filtered and evaporated, yielding 32.20 g of the desired product 49-a (99.8%). m/z=206.96 (M+1)+
	With bromine; sodium acetate; acetic acid; at 20℃; for 18h;	To a mixture of 6-chloropyridin-3-amine (5 g, 38.9 mmol) and NaOAc (6.37 g, 77.8 mmol) in AcOH (30 mL) was added a solution of bromine (6.8 g, 42.8 mmol) in AcOH(5 mL) . The resulting reaction mixture was stirred at room temperature for 1 8hrs. Acetic acid was removed under reduced pressure to give the residue, which was dissolved into EA (50 mL), washed by NaHCO3 aqueous (20 mL x 5), water and brine. The organic layers was dried over Na2SO4, and the drying agent was filtered off. The filtrate was concentrated in vavuo to give the crude product, which was purified by silica gel chromatography (silica gel, eluting with 5% methanol in DCM) to give (5 g, 62%) as an orange solid. HPLC/UV purity: 90%; LC-MS (ESI): 207.3 (M + 1).

References: [1]Patent: WO2012/80450,2012,A1 .Location in patent: Page/Page column 25.
[2]Patent: WO2013/186335,2013,A1 .Location in patent: Page/Page column 87.
[3]Patent: WO2013/186333,2013,A1 .Location in patent: Page/Page column 102.
[4]Patent: WO2014/60411,2014,A1 .Location in patent: Page/Page column 56.
[5]Patent: US2015/111868,2015,A1 .Location in patent: Paragraph 0856; 0857.
[6]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[7]Patent: WO2018/204176,2018,A1 .Location in patent: Paragraph 00471.

6
[ 1050501-88-6 ]
[ 1266114-83-3 ]

References: [1]Patent: WO2012/80450,2012,A1 .
[2]Patent: WO2013/186335,2013,A1 .
[3]Patent: WO2013/186333,2013,A1 .
[4]Patent: WO2014/60411,2014,A1 .
[5]Patent: US2015/111868,2015,A1 .

7
[ 1050501-88-6 ]
[ 1383252-82-1 ]

References: [1]Patent: WO2012/80450,2012,A1 .
[2]Patent: WO2014/60411,2014,A1 .

8
[ 1050501-88-6 ]
[ 1383252-83-2 ]

References: [1]Patent: WO2012/80450,2012,A1 .
[2]Patent: WO2014/60411,2014,A1 .

9
[ 1050501-88-6 ]
[ 1199556-78-9 ]
C₂₀H₂₁ClN₂O₄ [ No CAS ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[2]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

10
[ 1050501-88-6 ]
[ 1199556-79-0 ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[2]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

11
[ 1050501-88-6 ]
[ 1199557-01-1 ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[2]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

12
[ 1050501-88-6 ]
[ 1370618-02-2 ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[2]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

13
[ 1050501-88-6 ]
[ 1199557-02-2 ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[2]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

14
[ 1050501-88-6 ]
tert-butyl {trans-3-Hydroxy-3-methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutyl}carbamate [ No CAS ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[2]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

15
[ 1050501-88-6 ]
trans-3-mmino-3-{4-[1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a][1,5]naphthyridin-7-yl]phenyl}-1-methylcyclobutanol [ No CAS ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[2]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

16
[ 1050501-88-6 ]
[ 1199557-04-4 ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.
[2]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

17
[ 24424-99-5 ]
[ 1050501-88-6 ]
[ 1227958-32-8 ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

18
[ 24424-99-5 ]
[ 1050501-88-6 ]
[ 1227958-32-8 ]
C₁₅H₂₀BrClN₂O₄ [ No CAS ]

References: [1]Organic Process Research and Development,2012,vol. 16,p. 1069 - 1081.

19
[ 1050501-88-6 ]
methyl 5-chloro-1-(4,4,4-trifluorobutyl)-1H-pyrrolo[3,2-b ]pyridine-2-carboxylate [ No CAS ]

References: [1]Patent: WO2013/186335,2013,A1 .
[2]Patent: WO2013/186333,2013,A1 .
[3]Patent: US2015/111868,2015,A1 .

20
[ 1050501-88-6 ]
(5-chloro-1-(4,4,4-trifluorobutyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)methanol [ No CAS ]

References: [1]Patent: WO2013/186335,2013,A1 .
[2]Patent: WO2013/186333,2013,A1 .
[3]Patent: US2015/111868,2015,A1 .

21
[ 1050501-88-6 ]
2-chloro-9-methoxybenzofuro[3,2-b]pyridine [ No CAS ]

References: [1]Patent: US2016/240800,2016,A1 .

22
[ 1050501-88-6 ]
2-(3-(1-(2,6-diisopropylphenyl)-1H-benzo[d]imidazol-2-yl)phenyl)-9-methoxybenzofuro[3,2-b]pyridine [ No CAS ]

References: [1]Patent: US2016/240800,2016,A1 .

23
[ 1050501-88-6 ]
2-(3-(1-(2,6-diisopropylphenyl)-1H-benzo[d]imidazol-2-yl)phenyl)benzofuro[3,2-b]pyridin-9-ol [ No CAS ]

References: [1]Patent: US2016/240800,2016,A1 .

24
[ 1050501-88-6 ]
C₃₆H₂₉N₃O₂Pt [ No CAS ]

References: [1]Patent: US2016/240800,2016,A1 .

25
[ 1050501-88-6 ]
[ 23112-96-1 ]
6-chloro-2-(2,6-dimethoxyphenyl)pyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
Ca. 100%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 3h;Inert atmosphere;	<strong>[1050501-88-6]2-bromo-6-chloropyridin-3-amine</strong> (4.52 g, 21.79 mmol), (2,6-dimethoxyphenyl)boronic acid (4.76 g, 26.1 mmol), Na2CO3 (4.62 g, 43.6 mmol), 1,2-dimethoxyethane (80 mL), and water (40 mL) were added to a 500 mL two-necked round-bottom flask equipped with a magnetic stir bar. The reaction mixture was degassed with N2 for 15 minutes. After this time. Pd(PPh3)4 (1.26 g, 1.09 mmol) was added and the reaction flask was placed into an oil bath and gradually heated to 90 C. for 3 hours. The reaction mixture was then cooled to room temperature (22 C.) and then diluted with ethyl acetate (EtOAc). The resulting mixture was then washed with brine and the separated organic layer were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was triturated with CH2Cl2 to yield the title compound as pale pink solid (4.0 g). The remaining filtrate was purified via flash chromatography on a 200 g column (50-75% EtOAc/Heptanes) to provide 6-chloro-2-(2,6-dimethoxyphenyl)pyridin-3-amine as a white solid (2.5 g) (overall yield 100% yield).

References: [1]Patent: US2016/240800,2016,A1 .Location in patent: Paragraph 0129.

26
[ 110-81-6 ]
[ 1050501-88-6 ]
2-bromo-6-chloro-3-ethylsulfanyl-pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With tert.-butylnitrite; In 1,2-dichloro-ethane; at 20 - 40℃;	t-butyl nitrite (5.15 g, 45 mmol, 1.5 eq) was added to a solution of 54 diethyldisulfide (7.3 g, 60 mmol, 2 eq) dissolved in 55 dichloroethane (100 ml), and then heated to 40 C. 56 <strong>[1050501-88-6]3-amino-2-bromo-6-chloropyridine</strong> (6.18 g, 30 mmol, 1.0 eq) was dropwise added thereto, and then stirred overnight at room temperature. 33 Water was added to the reaction solution mentioned above, and then extraction with chloroform was carried out. The obtained organic layer was washed with a saturated aqueous solution of 24 sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective 57 product was obtained in an amount of 4.02 g (yield 53%).1H-NMR of the obtained objective product is shown below.1H-NMR (400 MHz, CDCl3) delta: 7.42 (1H, d), 7.26 (1H, d), 2.95 (2H, q), 1.39 (3H, t).
4 g		Step P2.01 : Preparation of 2-bromo-6-chloro- -ethylsulfanyl-pyridine (0638) A solution of (ethyldisulfanyl)ethane (48 mmol, 5.9 g, 5.9 mL) and tert-butyl nitrite (36 mmol, 3.7 g, 4.3 mL) in 1 ,2-dichloroethane (100 ml) was heated at 40C. To this solution was added, slowly over 60 min, a solution of <strong>[1050501-88-6]2-bromo-6-chloro-pyridin-3-amine</strong> (commercialy available (CAS 1050501-88-6), 24 mmol, 5.0 g) in 1 ,2-dichloroethane (100 ml). The reaction was stirred at 40C for 3 h. Then, the reaction was diluted with water (10 ml), extracted with ethyl acetate (3x30 ml). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by combiflash (silica gel, 20% EA-cyclohexane) to afford 2-bromo-6-chloro-3- ethylsulfanyl-pyridine (16 mmol, 4.0 g). -NMR (CDCb, ppm) delta 7.42 (d, 1 H), 7.25(d, 1 H), 2.95 (q, 2H), 1.38 (t, 3H).

References: [1]Patent: US2019/185459,2019,A1 .Location in patent: Paragraph 0530; 0531; 0532; 0533.
[2]Patent: WO2017/134066,2017,A1 .Location in patent: Page/Page column 67-68.

27
[ 1050501-88-6 ]
2-bromo-6-chloro-3-ethylsulfonyl-pyridine [ No CAS ]