[ CAS No. 5140-72-7 ] {[proInfo.proName]}

Name: 5140-72-7|2-Bromo-6-chloropyridine|98%
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SKU: A394757
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Quality Control of [ 5140-72-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 5140-72-7 ]

Product Details of [ 5140-72-7 ]

CAS No. :	5140-72-7	MDL No. :	MFCD00181262
Formula :	C₅H₃BrClN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JWTZSVLLPKTZJP-UHFFFAOYSA-N
M.W :	192.44	Pubchem ID :	78820
Synonyms :

Calculated chemistry of [ 5140-72-7 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	36.95
TPSA :	12.89 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.9 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.97
Log Po/w (XLOGP3) :	2.21
Log Po/w (WLOGP) :	2.5
Log Po/w (MLOGP) :	1.85
Log Po/w (SILICOS-IT) :	2.76
Consensus Log Po/w :	2.26

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.98
Solubility :	0.201 mg/ml ; 0.00105 mol/l
Class :	Soluble
Log S (Ali) :	-2.12
Solubility :	1.48 mg/ml ; 0.00767 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.5
Solubility :	0.0614 mg/ml ; 0.000319 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.93

Safety of [ 5140-72-7 ]

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

Application In Synthesis of [ 5140-72-7 ]

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

Upstream synthesis route of [ 5140-72-7 ]
Downstream synthetic route of [ 5140-72-7 ]

[ 5140-72-7 ] Synthesis Path-Upstream 1~13

1
[ 5140-72-7 ]
[ 124-38-9 ]
[ 4684-94-0 ]

Reference： [1] Archiv der Pharmazie, 2000, vol. 333, # 5, p. 107 - 112

2
[ 5140-72-7 ]
[ 2258-42-6 ]
[ 4684-94-0 ]

Reference： [1] Synthetic Communications, 2012, vol. 42, # 5, p. 658 - 666

3
[ 5140-72-7 ]
[ 80099-98-5 ]

Reference： [1] Archiv der Pharmazie, 2000, vol. 333, # 5, p. 107 - 112

4
[ 5140-72-7 ]
[ 53344-72-2 ]

Yield	Reaction Conditions	Operation in experiment
35%	at 100℃;	The 6,6'-dichloro-2,2'-bipyridine 52a can also be prepared via Stille heterocoupling between the 2-bromo-6-chloropyridine 55 and the 2-chloro-6-tributylstannylpyridine 56, with a yield of 35percent (Scheme 25).

Reference： [1] Organic Letters, 2000, vol. 2, # 6, p. 803 - 805
[2] Patent: US2010/298562, 2010, A1, . Location in patent: Page/Page column 34

5
[ 109-09-1 ]
[ 5140-72-7 ]

Reference： [1] Organic Letters, 2000, vol. 2, # 6, p. 803 - 805
[2] Tetrahedron, 2006, vol. 62, # 26, p. 6166 - 6171

6
[ 626-05-1 ]
[ 5140-72-7 ]

Reference： [1] Dalton Transactions, 2015, vol. 44, # 36, p. 15905 - 15913
[2] European Journal of Organic Chemistry, 2002, # 2, p. 327 - 330
[3] Tetrahedron, 2003, vol. 59, # 50, p. 10043 - 10049

7
[ 40473-07-2 ]
[ 5140-72-7 ]

Reference： [1] Synthetic Communications, 1990, vol. 20, # 19, p. 2971 - 2977
[2] Journal of Chemical Research - Part S, 1996, # 4, p. 194 - 195

8
[ 4645-11-8 ]
[ 5140-72-7 ]

Reference： [1] Journal of Chemical Research - Part S, 1996, # 4, p. 194 - 195

9
[ 117068-71-0 ]
[ 5140-72-7 ]

Reference： [1] Journal of Chemical Research - Part S, 1996, # 4, p. 194 - 195

10
[ 626-05-1 ]
[ 5140-72-7 ]
[ 912934-77-1 ]

Reference： [1] Synlett, 2011, # 8, p. 1117 - 1120

11
[ 5140-72-7 ]
[ 39890-95-4 ]

Reference： [1] European Journal of Organic Chemistry, 2002, # 2, p. 327 - 330

12
[ 5140-72-7 ]
[ 258506-66-0 ]

Reference： [1] European Journal of Organic Chemistry, 2002, # 2, p. 327 - 330
[2] Dalton Transactions, 2015, vol. 44, # 36, p. 15905 - 15913

13
[ 626-05-1 ]
[ 5140-72-7 ]
[ 912934-77-1 ]

Reference： [1] Synlett, 2011, # 8, p. 1117 - 1120

[ 5140-72-7 ] Synthesis Path-Downstream 1~88

1
[ 40473-07-2 ]
[ 5140-72-7 ]

Reference： [1]Synthetic Communications,1990,vol. 20,p. 2971 - 2977
[2]Journal of Chemical Research - Part S,1996,p. 194 - 195

2
[ 4645-11-8 ]
[ 5140-72-7 ]

Reference： [1]Journal of Chemical Research - Part S,1996,p. 194 - 195

3
[ 117068-71-0 ]
[ 5140-72-7 ]

Reference： [1]Journal of Chemical Research - Part S,1996,p. 194 - 195

4
[ 24252-37-7 ]
[ 5140-72-7 ]
[ 225112-16-3 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1999,vol. 64,p. 377 - 388

5
[ 5140-72-7 ]
[ 124-38-9 ]
[ 4684-94-0 ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 107 - 112

6
[ 5140-72-7 ]
2-chloro-6-(tributylstannyl)pyridine [ No CAS ]
[ 53344-72-2 ]

Yield	Reaction Conditions	Operation in experiment
35%	tetrakis(triphenylphosphine) palladium(0); In toluene; at 100℃;	The 6,6'-dichloro-2,2'-bipyridine 52a can also be prepared via Stille heterocoupling between the 2-bromo-6-chloropyridine 55 and the 2-chloro-6-tributylstannylpyridine 56, with a yield of 35% (Scheme 25).

Reference： [1]Organic Letters,2000,vol. 2,p. 803 - 805
[2]Patent: US2010/298562,2010,A1 .Location in patent: Page/Page column 34

7
[ 5140-72-7 ]
[ 258506-66-0 ]

Reference： [1]European Journal of Organic Chemistry,2002,p. 327 - 330
[2]Dalton Transactions,2015,vol. 44,p. 15905 - 15913

8
[ 5140-72-7 ]
2-(6-chloro-pyridin-2-yl)-6-methyl-[1,3,6,2]dioxazaborocane [ No CAS ]

Reference： [1]Tetrahedron,2003,vol. 59,p. 10043 - 10049

9
[ 5140-72-7 ]
[ 39890-95-4 ]

Reference： [1]European Journal of Organic Chemistry,2002,p. 327 - 330

10
[ 5140-72-7 ]
3-(6-chloro-pyridin-2-yl)-8-aza-bicyclo[3.2.1]oct-2-ene [ No CAS ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 167 - 174
[2]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 55 - 58

11
[ 5140-72-7 ]
3-(6-chloro-pyridin-2-yl)-8-methyl-8-aza-bicyclo[3.2.1]oct-2-ene [ No CAS ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 167 - 174
[2]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 55 - 58

12
[ 5140-72-7 ]
[ 259522-28-6 ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 167 - 174
[2]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 55 - 58

13
[ 5140-72-7 ]
6-chloro-1'-methyl-1',2',5',6'-tetrahydro-[2,3']bipyridinyl [ No CAS ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 167 - 174

14
[ 5140-72-7 ]
6-chloro-1'-methyl-[2,3']bipyridinyl-1'-ium; iodide [ No CAS ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 167 - 174

15
[ 5140-72-7 ]
[ 80099-98-5 ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 107 - 112

16
[ 5140-72-7 ]
1-[(6-chloropyridin-2-yl)methyl]-4-methylpiperazine [ No CAS ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 107 - 112

17
[ 5140-72-7 ]
[ 783293-16-3 ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 107 - 112

18
[ 5140-72-7 ]
4-(6-chloro-pyridine-2-carbonyl)-piperazine-1-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 107 - 112

19
[ 5140-72-7 ]
[4-(6-chloro-pyridine-2-carbonyl)-piperazin-1-yl]-(6-chloro-pyridin-2-yl)-methanone [ No CAS ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 107 - 112

20
[ 5140-72-7 ]
[ 225112-32-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,1999,vol. 36,p. 1017 - 1022

21
[ 5140-72-7 ]
2-chloro-6-(4-ethoxycarbonyloxy-1-methylpiperidin-4-yl)pyridine hydrochloride [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1999,vol. 36,p. 1017 - 1022

22
[ 5140-72-7 ]
(6-Chloro-2-pyridyl)(1-methyl-4-piperidyl)methanol [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1999,vol. 64,p. 377 - 388

23
[ 5140-72-7 ]
1-(6-Chloro-2-pyridyl)-1-(1-methyl-4-piperidyl)ethanol [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1999,vol. 64,p. 377 - 388

24
[ 5140-72-7 ]
(E)-6-Chloro-2-pyridyl 1-methyl-4-piperidyl ketone oxime [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1999,vol. 64,p. 377 - 388

25
[ 5140-72-7 ]
(Z)-6-Chloro-2-pyridyl 1-methyl-4-piperidyl ketone oxime [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1999,vol. 64,p. 377 - 388

26
[ 5140-72-7 ]
(6-Chloro-2-pyridyl)(1-methyl-4-piperidyl)phenylmethanol [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1999,vol. 64,p. 377 - 388

27
[ 5140-72-7 ]
[ 98-80-6 ]
[ 13382-54-2 ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 90℃; for 1h;	<strong>[5140-72-7]2-Bromo-6-chloropyridine</strong> (3.0 g, 15.55 mmol) and phenylboronic acid (1.896 g, 15.55 mmol) were solvated in a mixtureof EtOH, toluene and water (2: 1: 1; 120 mL). Aqueous 1MNa2CO3 (15.55 mL, 31.10 mmol) and 5 mole percent of Tetrakis (triphenyl) phosphine)-palladium(0) (0.896 g, 0.775 mmol) were added under a nitrogen atmosphere. The reaction was refluxed at90 C for one hour. Water (20 mL) was added to quench the reaction, and the aqueous layer was extracted with diethyl ether (4 x 25 mL). The organic layer was then washed with brine, dried overMgS04, and concentrated in vacuo. The crude mixture was purified by a Biotage 40S column (eluted 2%-10% ethyl acetate in hexanes), to afford the pure titled compound (1.45 g, 74%). 'H NMR:8 7.24-7. 26 (m, 1H), 7.42-7. 48 (m, 3H), 7.63-7. 70 (m, 2H), 7.98-8. 00 (m, 2H); LC/MS rt-min(MIT) : 2.04 (190.18) (method A)
51%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In toluene; at 80℃; for 24h;Inert atmosphere;	<strong>[5140-72-7]2-bromo-6-chloropyridine</strong> (21.2 g, 0.11 mol)Phenylboronic acid (12.2 g, 0.10 mol)Palladium tetrakis triphenylphosphine 0.5g,Add to 1000ML reaction flask, add toluene 400ML,Aqueous sodium carbonate solution (2N, 150 mL) was treated with nitrogen and the oil bath was reacted at 80 C for 24 hours.Post-treatment: cooling, static 30 minutes to remove the liquid, keep the organic layer, spin dry toluene, solid plus dichloromethane dissolved, column separation, PE: DCM = 1: 1 column, was A-1 (9.6g, Y = 51%)

Reference： [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 547-548
[2]Patent: CN105198875,2017,B .Location in patent: Paragraph 0083-0085

28
[ 5140-72-7 ]
[ 937201-79-1 ]
[ 100243-39-8 ]
[ 937189-11-2 ]

Yield	Reaction Conditions	Operation in experiment
		Example 1-7; 4-(3,5-dimethoxy-phenyl)-2-[6-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridin-2-yl]-2,5,6,7-tetrahydro-cyclopenta[d]pyridazin-1-one; [Show Image] To a solution of 4-(3,5-dimethoxy-phenyl)-2,5,6,7-tetrahydro-cyclopenta[d]pyridazin-1-one (93 mg) obtained by a method similar to the method in Example 1-1 in N,N-dimethylformamide (1.3 mL) were added <strong>[5140-72-7]2-bromo-6-chloropyridine</strong> (79 mg) obtained in supplementary step 1 and potassium carbonate (71 mg) and the mixture was stirred at 120C for 16 hr. The mixture was allowed to return to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The obtained residue was dissolved in N,N-dimethylacetamide (1 mL). (S)-3-hydroxy-pyrrolidine (56 mg) was added, and the mixture was stirred at 120C for 5.5 hr. The reaction mixture was diluted with ethyl acetate and washed 4 times with brine. The organic layer was dried, concentrated and purified by silica gel column chromatography (chloroform:acetone=2:1-chloroform:methanol=10:1) to give 4-(3,5-dimethoxy-phenyl)-2-[6-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridin-2-yl]-2,5,6,7-tetrahydro-cyclopenta[d]pyridazin-1-one (47 mg). 1H-NMR(CDCl3) delta: 7.58(dd,1H,J=8.3,7.4Hz), 6.77-6.75(m,3H), 6.50(t,1H,J=2.3Hz), 6.41(d,1H,J=8.3Hz), 4.59-4.55(m,1H), 3.81(s,6H), 3.67-3.53(m,4H), 3.06(t,2H,J=7.5Hz), 3.01(t,2H,J=7.7Hz), 2.20-2.03(m,4H), 1.81(br s,1H).

Reference： [1]Patent: EP1953147,2008,A1 .Location in patent: Page/Page column 216

29
[ 5140-72-7 ]
[ 1160918-11-5 ]
[ 1160919-04-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;palladium diacetate; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 100℃;	<strong>[5140-72-7]2-Bromo-6-chloropyridine</strong> (.66 mmol, 126 mg), 4-[(4-methyl-1H-indol-5-yl)amino]-5- vinylnicotinonitrile (.55 mmol, 150 mg), Pd(OAc)2 (0.055 mmol, 12 mg), triethylamine (1.6 mmol, 160 mg), and P(o-ToI)3 (0.11 mmol, 33 mg) were heated to 100 C in 5 ml_ DMF overnight. An additional 50 mg of <strong>[5140-72-7]2-bromo-6-chloropyridine</strong> was added and the heating was continued for 2 h. The reaction was filtered and the filtrate was purified by reverse-phase chromatography (acetonitrile/water). The product fractions were concentrated the material was treated with 10 mL ethanol and heated gently for a few minutes. After cooling to room temperature and filtering, 65 mg of the title compound was obtained as a yellow solid. HPLC: 91.4%, rt = 9.2 min; HRMS: calculated 386.11670; found 386.11598.

Reference： [1]Patent: WO2009/76602,2009,A1 .Location in patent: Page/Page column 144-145

30
[ 5140-72-7 ]
[ 5509-65-9 ]
[ 1255945-82-4 ]

Yield	Reaction Conditions	Operation in experiment
47%	With tris-(dibenzylideneacetone)dipalladium(0); 2,2?-bis(diphenylphosphino)-1,1?-binaphthalene.; sodium t-butanolate; In toluene; at 70℃; for 7h;Inert atmosphere;	Example 1 W-(5-fert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-2-(3-{6-[1 -(2,6-difluoro-phenyl)- ureido]-pyridin-2-yl}-phenyl)-acetamidea. (6-Chloro-pyridin-2-yl)-(2,6-difluoro-phenyl)-amineA solution of <strong>[5140-72-7]2-<strong>[5140-72-7]bromo-6-chloro-pyridine</strong></strong> (3.0 g, 15.6 mmol), 2,6- difluoroaniline (1.76 ml_, 16.37 mmol), tris(dibenzylideneacetone)dipalladium(0) (285 mg, 0.31 mmol), BINAP (388 mg, 0.62 mmol) and sodium fe/f-butoxide (2.1 g, 21.83 mmol) in toluene (50 ml_) was purged with argon, stirred at 700C for 7 h then allowed to cool down to RT. The reaction mixture was partitioned between diethyl ether and water. The aqueous layer was extracted twice with diethyl ether, the combined organic layers were washed with brine, dried (MgSO4), concentrated in vacuo and purified twice by chromatography (0 to 10% ethyl acetate in cyclohexane then 0 to 30% DCM in cyclohexane) to give the title compound as a white solid (1.78 g, 47%). LCMS (Method 1 ): Rt 4.55 min, m/z 241/243 [MH+]. 1H NMR (400 MHz, DMSO-d6): 8.90 (1 H, s), 7.57 (1 H, dd, J 8.2, 7.5), 7.34-7.25 (1 H, m), 7.21-7.13 (2 H, m), 6.77 (1 H, dd, J 7.5, 0.6), 6.63 (1 H, d, J 8.2).

Reference： [1]Patent: WO2010/131030,2010,A1 .Location in patent: Page/Page column 20; 21

31
[ 626-05-1 ]
[ 5140-72-7 ]
[ 912934-77-1 ]

Reference： [1]Synlett,2011,p. 1117 - 1120

32
[ 5140-72-7 ]
[ 2258-42-6 ]
[ 4684-94-0 ]

Reference： [1]Synthetic Communications,2012,vol. 42,p. 658 - 666

33
[ 5140-72-7 ]
[ 132559-91-2 ]
[ 1357190-69-2 ]

Reference： [1]Synlett,2011,p. 2867 - 2871

34
[ 5140-72-7 ]
potassium 6-chloropyridine-2-trifluoroborate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%		General procedure: A 100 mL single-neck flask was evacuated under vacuum, flame-dried and then charged with nitrogen gas three times. Anhydrous THF was added to the flask via syringe and a solution of a variety of functional groups 2-bromopyridine (1.0 equiv) in THF was added following by triisopropyl borate (1.1 equiv) via syringe at -78 C. A solution of 2.5 M n-BuLi in hexane (1.1 equiv) was added dropwise via constant pressure funnel over 2.0 h at -78 C. After the addition of n-BuLi was complete, the mixture was kept at -78 C with stirring for an additional 3.0 h, then allowed to warm up room temperature overnight. The mixture was then cooled to 0 C and an aqueous solution of KHF2 (3.0 equiv) was added dropwise with vigorous stirring. After stirring for an additional 4.0 h, the solvents were completely removed under vacuum. The crude product was then taken up in methanol and filtered, elimination of the solvent of methanol gave the white solid, and then the white solid was washed with acetone and filtered, collected, and dried in vacuo to afford the desired pure product as a light white solid (A-E).

Reference： [1]Tetrahedron,2012,vol. 68,p. 1351 - 1358

35
[ 5140-72-7 ]
[ 1359761-06-0 ]
[ 1359759-10-6 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 125 - 150℃; for 0.75h;Microwave irradiation;	5-(6-chloropyridin-2-yl)-l-(2,2-dimethyipropyl)-3-methyl-1 -dihydro~2H-benzimidazol~2- one (5-2)Cesium carbonate (852 mg, 2.61 mmol, 3.0 eq) was added to a solution of l-(2,2- dimethylpropyl)-3-methyl-5-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-l,3-dihydro-2H- benzimidazol-2-one (5-1, 300 mg, 0.87 mmol) dissolved in anhydrous Dioxane (5 ml). 2-Chloro- 4-hydroxybenzonitrile (335 mg, 1.74 mmol, 2.0 eq) was introduced followed by Iota,Gamma- Bis(diphenylphosphino) ferrocene-palladium(II)dichloride dichloromethane complex (35.6 mg, 0.04 mmol, 0.05 eq). The reaction mixture was irradiated at 125 deg C for 15 min. The reaction not complete, so more 2-Chloro-4-hydroxybenzonitrile (335 mg, 1.74 mmol, 2.0 eq) and Pd catalyst (35.6 mg, 0.04 mmol, 0.05 eq) was added and the reaction was irradiated again at 150 deg C for 30 min. The reaction was partitioned between EtOAc (2x100 ml) and saturated aqueous NaHC03 (90 ml). The combined organic layers were dried over Na2S04 andconcentrated, and the crude product was purified via flash column chromatography (Si02: 100% Hex to 60:40 Hex/ EtOAc), providing 5-(6-chloropyridin-2-yl)-l-(2,2-dimethylpropyl)-3-methyl- l,3-dihydro-2H-benzimidazol-2-one (5-2) as a yellow. 1HNMR (500 MHz, CDC13) delta 7.70-7.63 (m, 4H), 7.22 (d, 2H, J=6.8 Hz), 7.07 (d, 1H, J-8.3 Hz), 3.69 (s, 2H), 3.50 (s, 3H), 1.05 (s, 9H). LRMS m/z: Calc'd for C18H20ClN3O (M+H) 330.8, found 330.1.

Reference： [1]Patent: WO2012/21382,2012,A1 .Location in patent: Page/Page column 99

36
[ 5140-72-7 ]
3,5-dimethyl-2-iodopyridine [ No CAS ]
[ 1373615-88-3 ]

Yield	Reaction Conditions	Operation in experiment
59%		An oven-dried flask under N2 was charged with TMS-CH2Li (2.57 mmol, 1 M in pentane) and cooled to 0 C. Then a solution of the 2-iodo-3,5-dimethylpyridine (300 mg, 1 .29 mmol) in heptane (4.3 mL) was added dropwise, and the resulting mixture was stirred at 0 C for 1 h. The solution was cooled to -78 C, and 2 mL THF was added. A solution of ZnBr2 (435 mg, 1 .53 mmol) in THF (4.3 mL, cooled to 0 C) was added dropwise. The resulting mixture was stirred vigorously at -78 C for 30 min, then warmed to 0 C for 1 h. Solid <strong>[5140-72-7]2-bromo-6-chloropyridine</strong> (371 mg, 1 .93 mmol) and Pd(PPh3) (74 mg, 5 mol%) were added. The reaction flask was evacuated and back-filled with N2 (3x) then heated to 65 C. After 20h, the reaction was removed from heat and quenched with saturated aqueous ammonium chloride. The biphasic mixture was transferred to a separation funnel and extracted with EtOAc (3x). The combined organics were washed with 1 M Na2S2O3, saturated aqueous sodium bicarbonate, water, and brine, then dried over MgSO4, filtered, and concentrated to get crude product. Purified on Biotage 40S column, eluting with 0-20% EtOAc/heptane to afford 166 mg (59%) of the title compound as an orange oil. LCMS and NMR showed desired product >95% pure, m/z (APCI+) for C12H11 N2CI = 219.00 (M+H)+. 1H NMR (400 MHz, DMSO-d6) delta ppm 8.36 (s, 1 H) 7.95 - 8.01 (m, 1 H) 7.88 - 7.94 (m, 1 H) 7.58 (s, 1 H) 7.53 (d, J=7.83 Hz, 1 H) 2.47 (s, 3 H) 2.33 (s, 3 H).

Reference： [1]Patent: WO2012/52948,2012,A1 .Location in patent: Page/Page column 65-66

37
[ 5140-72-7 ]
[ 75-04-7 ]
[ 89026-80-2 ]

Reference： [1]Tetrahedron,2012,vol. 68,p. 9009 - 9015

38
[ 5140-72-7 ]
[ 1401345-10-5 ]

Reference： [1]Patent: WO2012/129338,2012,A1

39
[ 5140-72-7 ]
[ 1401348-49-9 ]

Reference： [1]Patent: WO2012/129338,2012,A1

40
[ 5140-72-7 ]
[ 1401348-50-2 ]

Reference： [1]Patent: WO2012/129338,2012,A1

41
[ 5140-72-7 ]
[ 1401348-51-3 ]

Reference： [1]Patent: WO2012/129338,2012,A1

42
[ 41838-46-4 ]
[ 5140-72-7 ]
[ 1401732-14-6 ]

Reference： [1]Patent: WO2012/135631,2012,A1 .Location in patent: Page/Page column 19

43
[ 41838-46-4 ]
[ 5140-72-7 ]
[ 1249434-78-3 ]

Yield	Reaction Conditions	Operation in experiment
14%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 80℃;	EXAMPLE 10: 6-chloro-N-(l-methylpiperidin-4-yl)pyrazin-2-amine11To a stirred solution of 2-bromo-6-chloro pyridine (500mg, 2.58mmol) in DMF, DIPEA was added followed by 4-amino-N-methylpiperidine and was heated at 80 C overnight. Reaction mixture was concentrated and the residue was diluted with water and extracted with ethyl acetate (50ml), the extract was washed with water. The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated. Purification was done by flash column using 230- 400 mesh silica gel eluting with 10% MeOH/DCM system to afford the desired product 11, 95mg (Yield: 14 %) as pale yellow solid. LCMS confirms the mixture of Br/CI isomers, majorly compound 11. 1H NMR (400 MHz, DMSO-d6) delta: 8.41 (s, 1H), 7.95 (s, 1H), 3.70 (s, 4H), 2.89 (s, 2H), 2.73 (bs, 2H), 2.01 (s, 1H), 1.98 (bs, 3H); MS: 226.8 (M+l).

Reference： [1]Patent: WO2012/135631,2012,A1 .Location in patent: Page/Page column 20

44
[ 5140-72-7 ]
[ 98437-23-1 ]
2-(benzo[b]thiophen-2-yl)-6-chloropyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38.6%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate tribasic trihydrate; In 1,4-dioxane; at 100℃; for 15h;	To a degassed solution of benzo[b]thiophen-2-ylboronic acid (300 mg, 1.69 mmol) and 3-bromo-5-chloropyridine (270 mg, 1.40 mmol) in 1 , 4-Dioxane (20 mL) was addedKappa3Rho04·3Eta20 (900 mg, 3.37 mmol) under N2. Then Pd(dppf)Cl2 (10 mg) was added. After being allowed to stir at 100 C and allowed to stir at this temperature for about 15 hours, the reaction mixture was cooled to room temperature and concentrated and extracted with EtOAc. The organic layers were washed with brine, dried over Na2S04. After being concentrated in vacuo, the resulting residue was purified using column chromatography (eluted with PE : EtOAc = 5 : 1) to provide 3-(benzo[b]thiophen-2-yl)-5-chloropyridine as white solid (160 mg, yield: 38.6%). 1H-NMR (CDC13, 400 MHz) delta 8.43-8.45 (m, 1H), 7.71-7.78 (m, 4H), 7.27-7.32 (m, 2H), 7.13-7.14 (m, 1H). MS (M+H)+: 246.
38.6%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate tribasic trihydrate; In 1,4-dioxane; at 100℃; for 15h;	To a degassed solution of benzo[b]thiophen-2-ylboronic acid (300 mg, 1.69 mmol) and 3-bromo-5-chloropyridine (270 mg, 1.40 mmol) in 1 , 4-Dioxane (20 mL) was addedKappa3Rho04·3Eta20 (900 mg, 3.37 mmol) under N2. Then Pd(dppf)Cl2 (10 mg) was added. After being allowed to stir at 100 C and allowed to stir at this temperature for about 15 hours, the reaction mixture was cooled to room temperature and concentrated and extracted with EtOAc. The organic layers were washed with brine, dried over Na2S04. After being concentrated in vacuo, the resulting residue was purified using column chromatography (eluted with PE : EtOAc = 5 : 1) to provide 3-(benzo[b]thiophen-2-yl)-5-chloropyridine as white solid (160 mg, yield: 38.6%). 1H-NMR (CDC13, 400 MHz) delta 8.43-8.45 (m, 1H), 7.71-7.78 (m, 4H), 7.27-7.32 (m, 2H), 7.13-7.14 (m, 1H). MS (M+H)+: 246.

Reference： [1]Patent: WO2013/33901,2013,A1 .Location in patent: Page/Page column 36
[2]Patent: WO2013/34047,2013,A1 .Location in patent: Page/Page column 42-43

45
[ 5140-72-7 ]
[ 98437-23-1 ]
[ 1426939-95-8 ]

Reference： [1]Patent: WO2013/33901,2013,A1
[2]Patent: WO2013/34047,2013,A1

46
[ 5140-72-7 ]
N-(2,6-dimethylphenyl)-4-((6-(4-(trifluoromethoxy)phenyl)pyridin-2-yl)amino)benzamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6777 - 6783
[2]Patent: CN103864770,2019,B

47
[ 5140-72-7 ]
4-((6-(4-(trifluoromethoxy)phenyl)pyridin-2-yl)amino)benzoic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6777 - 6783
[2]Patent: CN103864770,2019,B

48
[ 5140-72-7 ]
methyl 4-((6-(4-(trifluoromethoxy)phenyl)pyridin-2-yl)amino)benzoate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6777 - 6783
[2]Patent: CN103864770,2019,B

49
[ 5140-72-7 ]
[ 139301-27-2 ]
2-chloro-6-(4-(trifluoromethoxy)phenyl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.4%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; In water; N,N-dimethyl-formamide; at 85℃; for 12h;Inert atmosphere;	<strong>[5140-72-7]2-Bromo-6-chloropyridine</strong> (453 mg, 1.1 eq),4-trifluoromethoxyphenylboronic acid (384 mg, 1 eq),Bistriphenylphosphine palladium dichloride (140 mg, 0.1 eq),Triethylamine (566 mg, 2.8 eq)And 2ml of water is added to 15ml DMF.Nitrogen protection,The reaction was carried out at 85 C for 12 h.Add water to the reaction solution,Extracted 3 times with dichloromethane,The organic layers were combined and washed with saturated sodium chloride for 3 times.The organic layer was dried over anhydrous sodium sulfate and filtered.Filtration concentrated column chromatography (petroleum ether / ethyl acetate = 100:1)White solid 428mg

Reference： [1]Patent: CN103864770,2019,B .Location in patent: Paragraph 1006-1010
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6777 - 6783

50
[ 5140-72-7 ]
[ 1211579-64-4 ]

Reference： [1]Patent: WO2014/99503,2014,A1

51
[ 5140-72-7 ]
[ 1616373-10-4 ]

Reference： [1]Patent: WO2014/99503,2014,A1

52
[ 5140-72-7 ]
[ 151073-69-7 ]
[ 1268520-42-8 ]

Yield	Reaction Conditions	Operation in experiment
1.4 g	With tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 20℃; for 2h;	Step 1: To a degassed (sparged) solution of <strong>[5140-72-7]2-bromo-6-chloropyridine</strong> (2.0 g, 10.4 mmol) in THF (75 mL) was added Pd(PPh3)4 (200 mg) followed by a solution of (4-ethoxy-4-oxobutyl)zinc(II) bromide (0.5M in THF; 20.8 mL, 20.8 mmol). After stirring at room temperature for 2 hrs, the solution was poured on to a mixture of ice and IN HC1, extracted with EtOAc, the organic phase separated, dried (MgS04), filtered and evaporated. The isolated residue was purified on silica gel (0 to 30% EtOAc in hexanes) to afford 1.4 g of ethyl 4-(6-chloropyridin-2-yl)butanoate

Reference： [1]Patent: WO2014/99503,2014,A1 .Location in patent: Paragraph 00144

53
potassium fluoride [ No CAS ]
[ 5140-72-7 ]
[ 1622923-36-7 ]
[ 1622923-55-0 ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 7604 - 7607
Angew. Chem.,2014,vol. 53-126,p. 7729 - 7733

54
[ 5140-72-7 ]
((3aS,5rs,6aR)-2,2-dimethyltetrahydrocyclopenta[1,3]dioxol-5-yl)methanol [ No CAS ]
2-bromo-6-((3aS,5rs,6aR)-2,2-dimethyltetrahydrocyclopenta[1,3]dioxol-5-ylmethoxy)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃;	To a solution of intermediate AJ.iii (300 mg) and <strong>[5140-72-7]2-bromo-6-chloropyridine</strong> (352 mg) in DMF (5 mL) at 0C was added NaH (60% suspension in oil, 105 mg). The reaction was stirred at rt overnight. The mixture was quenched with brine and extracted with EA. The org. layer was washed with water (3x), dried over MgS04, filtered and concentrated under reduced pressure. The residue was purified by CC (Combi Flash; gradient Hept to Hept-EA 80-20), affording a colourless oil (345 mg; 60% yield). MSI (ESI, m/z): 328.0 [M+H+]; tR = 0.92 min.

Reference： [1]Patent: WO2014/170821,2014,A1 .Location in patent: Page/Page column 104

55
[ 5140-72-7 ]
(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanone [ No CAS ]
(6-chloropyridin-2-yl)(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%		[00419] To a solution of 2-broroo~6~diloropyridine (83 mg, 0.43 mmol) its 2-MeTHF (1.5 mL) cooled to -78 C was added n-BuLi (1.6 M, 0.27 mh, 0.43 mmol) dropwise and the reaction was allowed to stir for 40 miss. A. solution of (6^3,5- iimethyMsoxazQl-4-yl)~2~ ethoxy- 1 H~benzo [d] imida oM-yl)(pyridm~2~yI)methanoxie (100 mg, 0.22 mmol) in 2~ MeTHF (0.5 mL) was added omicron the reaction and t reaction was allowed to stir for an additional 10 mws at -78 C and then quenched with water. The reaction mixture was extracted three times with. EtOAc and combined organic layers were washed once with water, concentrated, and purified by silica gel chromatography to yield (6-ehloropvTidm-2~yl)(6- (3,5- imethyHsQxaz0l-4-yl)-2-efe^ (51 mg, 41 %) as a white solid.

Reference： [1]Patent: WO2014/160873,2014,A1 .Location in patent: Paragraph 00419

56
[ 5140-72-7 ]
ethyl 6-(6-chloropyridin-2-yl)-5-fluoropyridazine-3-carboxylate [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 3414 - 3417
[2]Organic Letters,2015,vol. 17,p. 3414 - 3417

57
[ 5140-72-7 ]
[ 914950-09-7 ]

Reference： [1]Organic Letters,2015,vol. 17,p. 3414 - 3417

58
[ 5140-72-7 ]
C₈H₄ClF₂N [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 3414 - 3417
[2]Organic Letters,2015,vol. 17,p. 3414 - 3417

59
[ 5140-72-7 ]
[ 1066-54-2 ]
[ 1330043-85-0 ]