[ CAS No. 139022-25-6 ] {[proInfo.proName]}

Name: 139022-25-6|Imidazo[1,2-a]pyridine-6-carboxylic acid|97%
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SKU: A296542
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Quality Control of [ 139022-25-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 139022-25-6 ]

CAS No. :	139022-25-6	MDL No. :	MFCD07021498
Formula :	C₈H₆N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ONOJJCTXSDBVSP-UHFFFAOYSA-N
M.W :	162.15	Pubchem ID :	7075376
Synonyms :

Calculated chemistry of [ 139022-25-6 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	42.15
TPSA :	54.6 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) :	-6.37 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.19
Log Po/w (XLOGP3) :	1.29
Log Po/w (WLOGP) :	1.03
Log Po/w (MLOGP) :	0.32
Log Po/w (SILICOS-IT) :	0.29
Consensus Log Po/w :	0.82

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.15
Solubility :	1.16 mg/ml ; 0.00713 mol/l
Class :	Soluble
Log S (Ali) :	-2.04
Solubility :	1.49 mg/ml ; 0.0092 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.45
Solubility :	5.77 mg/ml ; 0.0356 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.33

Safety of [ 139022-25-6 ]

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 [ 139022-25-6 ]

* 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.

Upstream synthesis route of [ 139022-25-6 ]
Downstream synthetic route of [ 139022-25-6 ]

[ 139022-25-6 ] Synthesis Path-Upstream 1~9

1
[ 139022-25-6 ]
[ 132213-07-1 ]

Yield	Reaction Conditions	Operation in experiment
26%	With dimethylsulfide borane complex In tetrahydrofuran at 0 - 80℃; for 3.5 h;	To a solution of compound B-266 (4.3 g, 27 mmol) in anhydrous tetrahydrofuran (25 mL) was added borane dimethyl sulfide complex (5.8 mL, 10 N in dimethyl sulfide, 58 mmol) dropwise at 0 °C. The resulting solution was stirred at 0 °C for 0.5 hour, then heated to 80 °C and stirred at this temperature for 3 hours. On completion, the mixture was quenched with methanol (10 mL) at 0 °C, concentrated in vacuo and purified by silica gel chromatography [dichloromethane: methanol = 10: 1] to give compound B-267 (1.0 g, 26percent yield) as a white solid. LCMS: (ES⁺) m/z (M+H)⁺ = 149.1 , tR = 0.279.

Reference： [1] Patent: WO2015/66371, 2015, A1, . Location in patent: Paragraph 00530-00531

2
[ 1314777-15-5 ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium hydroxide In water	Step 2. Imidazo[ l ,2-a]pyridine-6-carboxylic acid hydrochloride salt ( 1 70 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 °C using an ice-H2O bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product ( 107.2 g, 77percent) as a light yellow powder. 1H NMR (400 MHz, DMSO-d6) 6 1 3.76-1 2.82 (br, 1 H), 9.28 (s, 1 H), 8. 10 (s, 1 H), 7.68 (s, 1 H), 7.64-7.56 (m, 2H). MS (ESI+) m z: 1 63 [M+H]
77%	With sodium hydroxide In water	Step 2. Imidazo[ l ,2-a]pyridine-6-carboxylic acid hydrochloride salt ( 1 70 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 °C using an ice-H>0 bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product ( 107.2 g, 77percent) as a light yellow powder. NMR (400 MHz, DMSO-c/_e) 6 1 3.76-1 2.82 (br, 1 H), 9.28 (s, 1 H), 8. 10 (s, 1 H), 7.68 (s, 1 H), 7.64-7.56 (m, 2H). MS (ES 1+) m z: 1 63 [M+H]^~
77%	With sodium hydroxide In waterHeating	Step 2. Imidazo[ l ,2-a]pyridine-6-carboxylic acid hydrochloride salt ( 1 70 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 °C using an ice-H>0 bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product ( 107.2 g, 77percent) as a light yellow powder. 1H NMR (400 MHz, DMSO-d6) 6 1 3.76-1 2.82 (br, 1 H), 9.28 (s, 1 H), 8. 10 (s, 1 H), 7.68 (s, 1 H), 7.64-7.56 (m, 2H). MS (ESI+) m z: 1 63 [M+H]

77%

With sodium hydroxide In water at 0℃;

Step 2. Imidazo[l,2-a]pyridine-6-carboxylic acid hydrochloride salt (170 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 °C using an ice-H₂0 bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product (107.2 g, 77percent) as a light yellow powder. 1H NMR (400 MHz, DMSO-J₆) δ 13.76-12.82 (br, 1H), 9.28 (s, 1H), 8.10 (s, 1H), 7.68 (s, 1H), 7.64-7.56 (m, 2H). MS (ESI+) m/z: 163 [M+H]⁺.

Reference： [1] Patent: WO2013/127266, 2013, A1, . Location in patent: Page/Page column 130
[2] Patent: WO2013/127267, 2013, A1, . Location in patent: Page/Page column 81; 82
[3] Patent: WO2013/127268, 2013, A1, . Location in patent: Page/Page column 59; 60
[4] Patent: WO2013/130943, 2013, A1, . Location in patent: Paragraph 0181

3
[ 158001-04-8 ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
78%	With lithium hydroxide monohydrate In tetrahydrofuran; water at 25℃; for 2 h;	To a solution of ethyl imidazo[l ,2-a]pyridine-6-carboxylate (6.0 g, 36 mmol) in tetrahydrofuran (30 mL) and water (30 mL) was added lithium hydroxide hydrate (2.7 g, 63 mmol). The reaction mixture was stirred at 25 °C for 2 hours. On completion, the mixture was acidified with 36percent hydrochloric acid. The solid was collected, washed with water and dried in vacuo to give compound B-266 (4.0 g, 78percent yield) as a yellow solid.

Reference： [1] Patent: WO2015/66371, 2015, A1, . Location in patent: Paragraph 00528-00529
[2] Patent: WO2018/64135, 2018, A1, . Location in patent: Paragraph 0287-0289

4
[ 3167-49-5 ]
[ 2032-35-1 ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
59%	Stage #1: at 90℃; for 2 h; Stage #2: With sodium hydrogencarbonate In water at 20 - 60℃; for 0.5 h;	[1148] A mixture of bromoacetaldehyde diethylacetal (8.0 ml, 52.5 mmol), H2O (60 ml), and conc. HCl (2.6 ml) is heated to 90° C. with an oil bath for 2 h. 6-aminonicotinic acid (2.5 g, 18.1 mmol) and sodium bicarbonate (4.3 g, 50.7 mmol) are added to the solution at rt, followed by heating the resulting mixture to 60° C. with an oil bath for 30 min. Upon cooling to rt a white ppt. is formed. The resulting off white solid is recrystallized from H2O/EtOH/Et2O to afford white crystals (2.3 g, 10.6 mmol, 59percent) for imidazo[1,2-a]pyridine-6-carboxylic acid. HRMS (FAB) calcd for C8H6N2O2+H 163.0508, found 163.0492.

Reference： [1] Patent: US2003/236264, 2003, A1, . Location in patent: Page 52

5
[ 136117-69-6 ]
[ 139022-25-6 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 3, p. 465 - 469
[2] Patent: WO2006/15737, 2006, A1, . Location in patent: Page/Page column 51-52

6
[ 3167-49-5 ]
[ 7252-83-7 ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
22%	With sodium hydrogencarbonate In water	A. Imidazo[1,2-a]pyridine-6-carboxylic acid Concentrated HCL (1.5 mL) was added to a solution of bromoacetaldehyde dimethylacetal in water (50 mL), and the reaction refluxed for 30 min. The reaction mixture was then cooled in an ice bath, and sodium bicarbonate (10 g, 0.12 mol) was added slowly. After the addition was complete, 6-aminonicotinic acid (10 g, 0.072 mol) was added, and the reaction stirred at ambient temperature overnight. The reaction was then filtered, and the solid washed with water, and dried in vaccuo to give imidazo[1,2-a]pyridine-6-carboxylic acid as a white solid (2.61 g, 22percent). ¹H NMR (250 MHz, DMSO): δ 9.30 (s, 1H), 8.13 (s, 1H), 7.68 (s, 1H), 7.64 (s, 2H).

Reference： [1] Patent: US2004/167160, 2004, A1,

7
[ 36052-24-1 ]
[ 139022-25-6 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 3, p. 465 - 469

8
[ 39658-41-8 ]
[ 139022-25-6 ]

Reference： [1] Patent: WO2018/64135, 2018, A1,

9
[ 1448536-61-5 ]
[ 139022-25-6 ]
[ 1362154-70-8 ]

Reference： [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 16, p. 6413 - 6433

[ 139022-25-6 ] Synthesis Path-Downstream 1~88

1
[ 6530-09-2 ]
[ 139022-25-6 ]
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 8219 - 8248

2
[ 36052-24-1 ]
[ 139022-25-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 465 - 469

3
[ 139022-25-6 ]
6-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-oxazol-2-yl]-imidazo[1,2-<i>a</i>]pyridine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 465 - 469

5
[ 849806-07-1 ]
[ 139022-25-6 ]
imidazo[1,2-a]pyridine-6-carboxylic acid (5-(3-fluorophenoxy)thiophene-2-ylmethyl) amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45.4%	With (benzotriazole-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 80℃; for 0.666667h;	Preparation Example Q+-1 Imidazo[1,2-a]pyridine-6-carboxylic acid (5-(3-fluorophenoxy)thiophene-2-ylmethyl) amide To a solution of <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (87mg, 0.54mmol) and C-(5-(3-fluorophenoxy)thiophen-2-yl)methylamine (120mg, 0.54mmol) in N,N-dimethylformamide (5mL) were added benzotriazol-1-yl-tris(dimethylamino)phosphonium hexafluorophosphate (240mg, 0.54mmol) and triethylamine(0.15mL, 1.08mmol), and the solution was stirred for 40 minutes at 80C. Water and ethyl acetate were added to the reaction mixture for extraction, and the organic layer was washed twice with water. Silica gel was added to the organic layer, solvent was evaporated in vacuo for adsorption, purification was carried out by silica gel column chromatography (hexane : ethyl acetate = 1 : 1, then ethyl acetate), and the title compound (90mg, 0.25mmol, 45.4%) was obtained as a light brown oil. 1H-NMR Spectrum (DMSO-d6) delta (ppm) : 4.55 (2H, d, J=5.6Hz), 6.58 (1H, d, J=4.0Hz), 6.83 (1 H, d, J=4.0Hz), 6.90-7.00 (3H, m), 7.40 (1 H, ddd, J=8.0, 8.0, 8.0Hz), 7.57-7.66 (3H, m), 8.04 (1 H, s), 9.12 (1 H, d, J=0.8Hz), 9.20 (1 H, t, J=5.6Hz).
45.4%	With (benzotriazole-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 80℃; for 0.666667h;	To a solution of <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (87mg, 0.54mmol) and C-(5-(3-fluorophenoxy)thiophen-2-yl)methylamine (120mg, 0.54mmol) in N,N-dimethylformamide (5mL) were added benzotriazol-1-yl-tris(dimethylamino)phosphonium hexafluorophosphate (240mg, 0.54mmol) and triethylamine(0.15mL, 1.08mmol), and the solution was stirred for 40 minutes at 80C. Water and ethyl acetate were added to the reaction mixture for extraction, and the organic layer was washed twice with water. Silica gel was added to the organic layer, solvent was evaporated in vacuo for adsorption, purification was carried out by silica gel column chromatography (hexane : ethyl acetate = 1 : 1, then ethyl acetate), and the title compound (90mg, 0.25mmol, 45.4%) was obtained as a light brown oil. 1H-NMR Spectrum (DMSO-d6) delta(ppm): 4.55 (2H, d, J=5.6Hz), 6.58 (1H, d, J=4.0Hz), 6.83 (1H, d, J=4.0Hz), 6.90-7.00 (3H, m), 7.40 (1H, ddd, J=8.0, 8.0, 8.0Hz), 7.57-7.66 (3H, m), 8.04 (1 H, s), 9.12 (1 H, d, J=0.8Hz), 9.20 (1 H, t, J=5.6Hz).

Reference： [1]Patent: EP1782811,2007,A1 .Location in patent: Page/Page column 62
[2]Patent: EP1669348,2006,A1 .Location in patent: Page/Page column 70

6
[ 139022-25-6 ]
[ 74-88-4 ]
[ 136117-69-6 ]

Yield	Reaction Conditions	Operation in experiment
39%	With caesium carbonate; In N,N-dimethyl-formamide;	B. Imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester Cesium carbonate (15.7 g, 48.2 mmol) and iodomethane (1.50 ml, 24.2 mmol) were added to a solution of <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (2.61 g, 16.1 mmol) in DMF (100 ml). The reaction was stirred at ambient temperature overnight, then poured into brine (100 ml) and extracted with ethyl acetate (3*100 mL). The combined organics were washed with saturated sodium bicarbonate solution (25 mL), and a 1N HCl solution (25 mL) then dried over MgSO4 and evaporated to give <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> methyl ester as a yellow solid (1.1 g, 39%). 1H NMR (250 MHz, CDCl3): delta 8.96 (s, 1H), 7.8-7.6 (m, 4H), 3.98 (s, 3H). MS [EI+] 177 (M+H)+.

Reference： [1]Patent: US2004/167160,2004,A1

7
[ 3167-49-5 ]
[ 7252-83-7 ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
22%	With sodium hydrogencarbonate; In water;	A. Imidazo[1,2-a]pyridine-6-carboxylic acid Concentrated HCL (1.5 mL) was added to a solution of bromoacetaldehyde dimethylacetal in water (50 mL), and the reaction refluxed for 30 min. The reaction mixture was then cooled in an ice bath, and sodium bicarbonate (10 g, 0.12 mol) was added slowly. After the addition was complete, 6-aminonicotinic acid (10 g, 0.072 mol) was added, and the reaction stirred at ambient temperature overnight. The reaction was then filtered, and the solid washed with water, and dried in vaccuo to give imidazo[1,2-a]pyridine-6-carboxylic acid as a white solid (2.61 g, 22%). 1H NMR (250 MHz, DMSO): delta 9.30 (s, 1H), 8.13 (s, 1H), 7.68 (s, 1H), 7.64 (s, 2H).

Reference： [1]Patent: US2004/167160,2004,A1

8
[ 67-56-1 ]
[ 139022-25-6 ]
[ 136117-69-6 ]

Yield	Reaction Conditions	Operation in experiment
	sulfuric acid;Heating / reflux;	General procedure for aryl/heteroaryl beta-ketonitrile synthesis (Al):Aryl or heteroaryl methyl carboxylate were commercially available or were synthesized according to the following standard procedure: the aryl or heteroaryl carboxylic acid (32 mmol) was dissolved in MeOH (40 niL) and sulfuric acid (ImL) was added. The mixture was refluxed overnight, after which the solvent was <n="42"/>evaporated under reduced pressure; the crude was dissolved in DCM and washed with saturated aqueous NaHCO3 solution. The organic phase was dried and evaporated under reduced pressure, and the crude was used without further purification.
		Aryl or heteroaryl methyl carboxylate were commercially available or were synthesized according to the following standard procedure: the aryl or heteroaryl carboxylic acid (32 mmol) was dissolved in MeOH (40 mL) and sulfuric acid (ImL) was added. The mixture was refluxed overnight, after which the solvent was evaporated under reduced pressure; the crude was dissolved in DCM and washed with saturated aqueous NaHCO3 solution. The organic phase was dried and evaporated under reduced pressure, and the crude was used without further purification.To a solution of an aryl or heteroaryl methyl carboxylate (6.5 mmol) in dry toluene (6 mL) under N2, NaH (50-60% dispersion in mineral oil, 624 mg, 13 mmol) was carefully <n="41"/>added. The mixture was heated at 80 0C and then dry CH3CN was added dropwise(1.6 mL, 30.8 mmol). The reaction was heated for 18 hours and generally the product precipitated from the reaction mixture as Na salt.[00164] The reaction was then allowed to cool down to room temperature and the solid formed was filtered and then dissolved in water. The solution was then acidified with 2N HCl solution and at pH between 2-6 (depending on the ring substitution on the aryl/heteroaryl system) the product precipitated and was filtered off. If no precipitation occurred, the product was extracted with DCM.[00165] After work-up, the products were generally used in the following step without further purification. The general yield was between 40 and 80%.; The product was obtained starting from imidazo[l,2-a]pyridine-6- carboxylic acid methyl ester according to general procedure AlYield 39%Ci0H7N3O Mass (calculated) [185]; (found) [M+H+]=186 [M-H]=I 84LC Rt=0.23, 100% (3 min method)IH-NMR: (dmso-d6): 4.72 (2H,s), 7.61-7.65 (2H, m), 7.70 (IH, m), 8.07 (IH, s), 9.40 (s,IH).

Reference： [1]Patent: WO2008/87529,2008,A1 .Location in patent: Page/Page column 40-41
[2]Patent: WO2009/91832,2009,A1 .Location in patent: Page/Page column 39; 43

9
[ 3167-49-5 ]
[ 2032-35-1 ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
59%		[1148] A mixture of bromoacetaldehyde diethylacetal (8.0 ml, 52.5 mmol), H2O (60 ml), and conc. HCl (2.6 ml) is heated to 90 C. with an oil bath for 2 h. 6-aminonicotinic acid (2.5 g, 18.1 mmol) and sodium bicarbonate (4.3 g, 50.7 mmol) are added to the solution at rt, followed by heating the resulting mixture to 60 C. with an oil bath for 30 min. Upon cooling to rt a white ppt. is formed. The resulting off white solid is recrystallized from H2O/EtOH/Et2O to afford white crystals (2.3 g, 10.6 mmol, 59%) for imidazo[1,2-a]pyridine-6-carboxylic acid. HRMS (FAB) calcd for C8H6N2O2+H 163.0508, found 163.0492.

Reference： [1]Patent: US2003/236264,2003,A1 .Location in patent: Page 52

10
[ 544-00-3 ]
[ 139022-25-6 ]
[ 1219715-66-8 ]

Yield	Reaction Conditions	Operation in experiment
		A suspension of <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (1.0 g), EDCI (1.775 g), HOBt (1.415 g) and N-methylmorpholine (1.0 ml) in DMF (20 ml) and DCM (5 ml) was stirred at 22C for 40 min. The resulting reddish solution was treated with diisopentylamine (1.9 ml) and N-methylmorpholine (1.0 ml) in this order and the reaction mixture was stirred at 22C for 24 h. The mixture was diluted with diethyl ether (100 ml) and washed with saturated sodium bicarbonate solution (2 x 60 ml). The combined aqueous layer was washed with diethyl ether (2 x 50 ml). The combined organic extract was washed with water (100 ml) and brine (100 ml), dried over sodium sulfate, filtered, and evaporated. The crude product was purified by column chromatography.

Reference： [1]Patent: EP2168965,2010,A1 .Location in patent: Page/Page column 29

11
[ 21103-33-3 ]
[ 139022-25-6 ]
N-4-(4-(2-methoxyphenyl)-piperazin-1-yl)-butyl-imidazo[1,2-a]pyridin-6-ylcarbamide [ No CAS ]

Reference： [1]Patent: WO2006/15737,2006,A1 .Location in patent: Page/Page column 81

12
[ 6610-31-7 ]
[ 139022-25-6 ]
[ 1220708-84-8 ]

Yield	Reaction Conditions	Operation in experiment
47%		To a stirred suspension of imidazo[1 ,2-a]pyridine-6-carboxylic acid (1 g, 6.2 mmol) in dioxane (12 ml) the title compound of Preparation 1 (0.91 g, 6.2 mmol) was added. To the suspension thus obtained POCI3 (1.73 ml, 18.6 mmol) was added dropwise at room temperature. The mixture was stirred at 70C for 3h under inert atmosphere. It was poured onto a mixture of a 2M aqueous solution of sodium hydroxide (50 ml) and ice (50 ml). The solid obtained was filtered, washed and dried to yield 792 mg (47%) of the title compound.LRMS: m/z 274 (M+1)+ Retention time: 2.08min (method A)1H NMR (200 MHz, DMSO-d6) delta ppm 0.98(t, J=8 Hz, 3H), 1.46(m, 2H), 1.69(m, 2H), 3.41 (t, J=8Hz, 2H), 5.48 (brs, 1 H), 7.65(m, 4H), 8.64(s, 1 H)
47%		PREPARATION 6 N-butyl-5-imidazo[1,2-a]pyridin-6-yl-1,3,4-thiadiazol-2-amine To a stirred suspension of <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (1 g, 6.2 mmol) in dioxane (12 ml) the title compound of Preparation 1 (0.91 g, 6.2 mmol) was added. To the suspension thus obtained POCl3 (1.73 ml, 18.6 mmol) was added dropwise at room temperature. The mixture was stirred at 70C for 3h under inert atmosphere. It was poured onto a mixture of a 2M aqueous solution of sodium hydroxide (50 ml) and ice (50 ml). The solid obtained was filtered, washed and dried to yield 792 mg (47%) of the title compound. LRMS: m/z 274 (M+1)+ Retention time: 2.08min (method A) 1H NMR (200 MHz, DMSO-d6) delta ppm 0.98(t, J=8 Hz, 3H), 1.46(m, 2H), 1.69(m, 2H), 3.41 (t, J=8Hz, 2H), 5.48 (brs, 1 H), 7.65(m, 4H), 8.64(s, 1 H)

Reference： [1]Patent: WO2011/69647,2011,A1 .Location in patent: Page/Page column 27
[2]Patent: EP2343287,2011,A1 .Location in patent: Page/Page column 18

13
1-methyl-1H-pyrrole-2-carboxylic acid ((S)-3-methylamino-4-phenylbutyl)amide hydrochloride [ No CAS ]
[ 139022-25-6 ]
[ 1312556-87-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 20h;	Example 1.2: (S)-N-methyl-N-f 4-f 1 -methyl-1 H-pyrrole-2-carboxamido)-1 -phenylbutan-2- l)imidazori,2-a1pyridine-6-carboxamide1 -Methyl-1 H-pyrrole-2-carboxylic acid ((S)-3-methylamino-4-phenyl-butyl)-amidehydrochloride (150 mg, 0.47 mmol), imidazo[1 ,2-a]pyridine-6-carboxylic acid (91 mg, 0.56 mmol), HOBt (86 mg, 0.56 mmol), EDC x HCI (134 mg, 0.70 mmol), and triethylamine (0.33ml, 2.33 mmol) were dissolved in DCM (15 ml) and stirred at rt for 20 h. The mixture was diluted with EtOAc, washed with NaHC03- and NaCI-soln., dried (Na2S04), filtered and concentrated. The crude product was purified by chromatography (Flashmaster, EtOAc 1 min, then EtOAc to EtOAc: MeOH 9:1 over 30 min) to yield 170 mg (85%) of the title compound as colorless solid. [1H-NMR (DMSO, 600 MHz, rotamers) 8.50-7.03 (m, 10H), 6.86 (s, 1 H), 6.83/6.53 (d, 1 H), 6.72/6.64 (s, 1 H), 5.99 (s, 1 H), 4.85/3.35 (br s, 1 H), 3.81/3.65 (s, 3H), 2.98/2.81 (s, 3H), 3.35-3.30/3.16-2.79 (m, 4H), 1.94-1.74 (m, 2H); LCMS RtB = 2.668 min; [M+H]+ = 430.2].

Reference： [1]Patent: WO2011/73316,2011,A1 .Location in patent: Page/Page column 82

14
[ 580-13-2 ]
[ 857003-04-4 ]
[ 139022-25-6 ]
N-(3-(naphthalen-2-ylsulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 2 NN-( 3-( naphthalen-2-ylsulfonyl)benzyl)imidazo [ 1 ,2-al pyridine-6-carboxamideTo a mixture of sodium 4-(acetamidomethyl)benzenesulfmate (0.2 M MeOH, 100 mu, 20 muiotaetaomicron) and zinc chloride (0.5 M THF, 40 mu, 20 muiotaetaomicron), cesium carbonate (1.43 M MeOH, 25 muEpsilon, 35 muiotaetaomicron) then 2-bromonapthelene (0.2 M Toluene, 110 mu, 22 muiotaetaomicron) were added. A toluene solution of XantPhos and Pd2dba (0.01 M XantPhos/0.005 M Pd2dba , 50 mu,, 2.5 mol%) was added and the reaction was heated for 4 h at 95 C under nitrogen. The reaction was cooled to room temperature and 70% i-PrOH (0.35 mL) and 3N HC1 (0.35 mL, 1.05 mmol) were added and was heated at 95 C for 4 hours then concentrated to dryness. The residue was treated with triethylamine (5%> in ACN (v/v), 100 mu) and imidazo[l,2-a]pyridine-6-carboxylic acid (0.2 M in DMA w/ 10% TEA (v/v), 120 mu, 24 muiotaetaomicron) and BOP (0.2 M DCE, 130 mu, 26 muiotaetaomicron). The solution was heated to 40 C for 4 h then cooled to room temperature and partitioned between NaOH and EtOAc. The organic layer was separated and deposited on a SCX-SPE cartridge which was eluted to two fractions: the Is with 25% MeOH/EtOAc (v/v), the 2nd with Et3N/MeOH/EtOAc (1 : 1 : 10 v/v/v). The second fraction was concentrated to dryness and was purified by LC/MS to afford the title compound as white solid.1H NMR (400 MHz, CDC13): delta 8.85 (s, 1H), 8.55 (s, 1H), 7.93 (m, 4H), 7.87 (d, J=8 Hz, 1H), 7.81 (dd, J=8.8 Hz, J'=1.6 Hz, 1H), 7.63 (m, 5H), 7.47 (d, J=8.4 Hz, 2H), 7.34 (m, 1H), 6.81 (m, 1H), 4.70 (d, J=5.6 Hz, 2H).LC-MS: 442.13 (M+l)

Reference： [1]Patent: WO2012/31197,2012,A1 .Location in patent: Page/Page column 409-410

15
[ 28599-52-2 ]
[ 857003-04-4 ]
[ 139022-25-6 ]
[ 1362160-35-7 ]

Reference： [1]Patent: WO2012/31197,2012,A1 .Location in patent: Page/Page column 408-409

16
[ 1362160-53-9 ]
[ 139022-25-6 ]
[ 1362148-89-7 ]

Yield	Reaction Conditions	Operation in experiment
15%	With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide;	c. N-(4-(5-(dimethylamino) pyrazin-2-ylsulfonyl) benzyl) imidazo [1, 2-al pyridine-6-carboxamide:In a 250 mL round-bottomed flask was added imidazo [1, 2-a] pyridine-6- carboxylic acid (0.592 g, 3.65 mmol), 5-(4-(aminomethyl) phenylsulfonyl)-N, N- dimethylpyrazin-2-amine, HCl (1.2 g, 3.65 mmol) and HBTU (1.522 g, 4.01 mmol), HOBT (0.615 g, 4.01 mmol) and DIEA (3.19 mL, 18.25 mmol) in DMF (50 mL). The reaction was stirred overnight and then concentrated under reduced pressure. The residue was diluted with methylene chloride and washed with 1M aq. NaOH. The organic layer was separated and concentrated and directly purified in the Biotage to give 235 mg of N-(4-(5-(dimethylamino) pyrazin-2-ylsulfonyl) benzyl) imidazo [1, 2-a] pyridine-6-carboxamide (15%).1HNMR (DMSO-d6): delta 9.21 (t, 1H), 9.13 (s, 1H), 8.67 (s, 1H), 8.12 (s, 1H), 8.95 (s, 1H), 7.86 (d, 2H), 7.63 (d, 2H), 7.54 (d, 2H), 4.53 (d, 2H), 3.11 (s, 6H).LC-MS: 437.0 (M+l)

Reference： [1]Patent: WO2012/31197,2012,A1 .Location in patent: Page/Page column 416-417

17
[ 1362160-59-5 ]
[ 139022-25-6 ]
[ 1362150-36-4 ]

Yield	Reaction Conditions	Operation in experiment
45%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	d: N-f4-ff3-ftrifluoromethoxy)phenyl)sulfonyl)benzyl)imidazo[l,2- alpyrimidine-6-carboxamide:A mixture of imidazo[l,2-a]pyrimidine-6-carboxylic acid (0.739 g, 4.53 mmol), (4-(3-(trifluoromethoxy)phenylsulfonyl)phenyl)methanamine (1.5 g, 4.53 mmol), BOP (2.203 g, 4.98 mmol) and DIEA (0.949 mL, 5.43 mmol) in DMF (25 mL) was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to remove the DMF. The residue was diluted with EtOAc and then washed with IN NaOH. The separated aqueous layer was back-extracted with EtOAc. The combined organic extracts were washed with 5% AcOH, water, brine and dried (Na2S04), filtered and concentrated. Purification by Biotage SP1 of the crude afforded the title compound as off-white solids (980 mg, 45% yield).1H NMR (300 MHz, DMSO-d6): delta 9.47(d, 1H), 9.35(t, 1H), 9.23(d, 1H), 8.01- 7.98(m, 5H), 7.80-7.3 l(m, 3H), 7.60(d, 2H), 4.57 (d, 2H).LC-MS: 476.87 (M+l).

Reference： [1]Patent: WO2012/31197,2012,A1 .Location in patent: Page/Page column 415

18
(4-(1-isopropyl-1H-pyrazol-4-ylsulfonyl)phenyl)methanamine hydrochloride [ No CAS ]
[ 139022-25-6 ]
[ 1362142-40-2 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide;	c. N-f4-fl-isopropyl-7H-pyrazol-4-ylsulfonyl) benzyl) imidazo [1, 2-al Pyridine-6-carboxamide:In a 250 mL round-bottomed flask were added imidazo[l,2-a]pyridine-6- carboxylic acid (0.719 g, 4.43 mmol), (4-(l-isopropyl-lH-pyrazol-4- ylsulfonyl)phenyl)methanamine, HC1 (1.4g , 4.43 mmol) and HBTU (1.849 g, 4.88 mmol), HOBT (0.747 g, 4.88 mmol) and DIEA (3.87 mL, 22.16 mmol) in DMF (Volume: 50 mL). The reaction was stirred overnight and then concentrated under reduced pressure. The residue was diluted with methylene chloride and washed with 1M aq. NaOH. The organic layer was separated and concentrated and directly purified in the Biotage to give 1.24 g of N-(4-(l-isopropyl-lH-pyrazol-4- ylsulfonyl) benzyl) imidazo [1, 2-a] pyridine-6-carboxamide.1HNMR (DMSO-D6): delta 9.20 (t, 1H), 9.13(s, 2H), 8.51 (s, 1H), 8.05 (s, 1H), 7.88- 7.91 (m, 3H), 7.53-7.67 (m, 4H), 4.42-4.55 (m, 3H), 1.37 (d, 6H).LC-MS: 424.01 (M+l)

Reference： [1]Patent: WO2012/31197,2012,A1 .Location in patent: Page/Page column 407

19
[ 1374864-79-5 ]
[ 139022-25-6 ]
[ 1362156-73-7 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 6413 - 6433

20
[ 1448536-62-6 ]
[ 139022-25-6 ]
[ 1362150-86-4 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 6413 - 6433

21
[ 205259-71-8 ]
[ 139022-25-6 ]
[ 1362132-20-4 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 6413 - 6433

22
[ 1314777-15-5 ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium hydroxide; In water;	Step 2. Imidazo[ l ,2-a]pyridine-6-carboxylic acid hydrochloride salt ( 1 70 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 C using an ice-H2O bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product ( 107.2 g, 77%) as a light yellow powder. 1H NMR (400 MHz, DMSO-d6) 6 1 3.76-1 2.82 (br, 1 H), 9.28 (s, 1 H), 8. 10 (s, 1 H), 7.68 (s, 1 H), 7.64-7.56 (m, 2H). MS (ESI+) m z: 1 63 [M+H]
77%	With sodium hydroxide; In water;pH 5-6;	Step 2. Imidazo[ l ,2-a]pyridine-6-carboxylic acid hydrochloride salt ( 1 70 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 C using an ice-H>0 bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product ( 107.2 g, 77%) as a light yellow powder. NMR (400 MHz, DMSO-c/e) 6 1 3.76-1 2.82 (br, 1 H), 9.28 (s, 1 H), 8. 10 (s, 1 H), 7.68 (s, 1 H), 7.64-7.56 (m, 2H). MS (ES 1+) m z: 1 63 [M+H]~
77%	With sodium hydroxide; In water;pH 5-6;Heating;	Step 2. Imidazo[ l ,2-a]pyridine-6-carboxylic acid hydrochloride salt ( 1 70 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 C using an ice-H>0 bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product ( 107.2 g, 77%) as a light yellow powder. 1H NMR (400 MHz, DMSO-d6) 6 1 3.76-1 2.82 (br, 1 H), 9.28 (s, 1 H), 8. 10 (s, 1 H), 7.68 (s, 1 H), 7.64-7.56 (m, 2H). MS (ESI+) m z: 1 63 [M+H]

77%

With sodium hydroxide; In water; at 0℃;pH 5 - 6;

Step 2. Imidazo[l,2-a]pyridine-6-carboxylic acid hydrochloride salt (170 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 C using an ice-H20 bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product (107.2 g, 77%) as a light yellow powder. 1H NMR (400 MHz, DMSO-J6) delta 13.76-12.82 (br, 1H), 9.28 (s, 1H), 8.10 (s, 1H), 7.68 (s, 1H), 7.64-7.56 (m, 2H). MS (ESI+) m/z: 163 [M+H]+.

Reference： [1]Patent: WO2013/127266,2013,A1 .Location in patent: Page/Page column 130
[2]Patent: WO2013/127267,2013,A1 .Location in patent: Page/Page column 81; 82
[3]Patent: WO2013/127268,2013,A1 .Location in patent: Page/Page column 59; 60
[4]Patent: WO2013/130943,2013,A1 .Location in patent: Paragraph 0181

23
[ 139022-25-6 ]
[ 1453174-87-2 ]

Reference： [1]Patent: WO2013/127266,2013,A1

24
[ 139022-25-6 ]
[ 1453176-75-4 ]

Reference： [1]Patent: WO2013/127266,2013,A1
[2]Patent: WO2013/127268,2013,A1

25
[ 139022-25-6 ]
[ 1453174-57-6 ]

Reference： [1]Patent: WO2013/127266,2013,A1

26
[ 1453176-72-1 ]
[ 139022-25-6 ]
[ 1453173-85-7 ]

Yield	Reaction Conditions	Operation in experiment
21%		Step 5. A solution of imidazo[ l ,2-a]pyridine-6-carboxylic acid (58 mg, 0.36 mmol, 1 .50 equiv), EDC1 (55 mg, 0.29 mmol, 1 .20 equiv), HOBt (39 mg, 0.29 mmol, 1.20 equiv), and DIPEA (93 mg, 0.72 mmol, 3.00 equiv) in DMF ( 10 mL) was stirred at 25 C for 10 min. 4-[4-(2,2,2-Trifluoro-ethyl)-piperazine-1-sulfonyl]-benzylamine (82 mg, 0 24 mmol, 1 .00 equiv) was then added and the mixture was stirred for 1 2 h at 25 C. The reaction was then quenched by the addition of 50 mL of water and the resulting solution was extracted with 2x50 mL of dichloromethane. The combined organic layers were washed with 100 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified on a silica gel column eluted with dichloromethane/methanol (100/5) to give 24.1 mg (21 %) of the title compound as a white solid. NMR (400 MHz, CDCh) delta 8.93 (s, 1 H), 7.69- 7.28 (m, 9H), 4.75 (s, 2H), 3.03-2.88 (m, 6H), 2.84-2.68 (m, 4H). LC/MS (Method B, ESI): RT= 1.93 min, m/z = 482.2 [M+H] + .

Reference： [1]Patent: WO2013/127266,2013,A1 .Location in patent: Page/Page column 150; 151; 152

27
[ 100-46-9 ]
[ 139022-25-6 ]
[ 1453176-74-3 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; at 20℃; for 24h;	To a mixture of benzylamine (2.62 g, 23.9 mmol), benzotriazol- l -yl-oxytripyrrolidinophosphonium hexafluorophosphate (6.42 g, 1 1 .96 mmol), and imidazo[l ,2-a]pyridine-6-carboxylic acid (2.00 g, 1 1 .96 mmol) in methylene chloride (100 mL), was added triethylamine ( 1 0.5 mL, 59.8 mmol). The reaction mixture was stirred at rt for 24 h and then concentrated to dryness under vacuum. The crude material was washed with an aqueous solution of saturated sodium bicarbonate (2x), water (2x), and ether (2x) The crude white solid was collected by filtration to yield the title compound (2.67 g, 89%). This material was used in the next step without further purification. NMR (400 MHz, DMSO-i/ft) delta 9.15 (s, 1 H), 9.1 1 (t, J = 5.8 Hz, 1 H), 8.06 (s, 1 H), 7 73-7.54 3 (m, 3H), 7.34 (d, J = 4.7 Hz, 4H), 7.28-7.16 (m, 1 H), 4.51 (d, J = 5.9 Hz, 2H). LC/MS (Method L, ESI): RT = 0.54 min, ,z = 252.2 [M + H]+ .
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; at 20℃; for 24h;	To a mixture of benzylamine (2.616 g, 23.93mmol), benzotriazol-1-yl- oxytripyrrolidinophosphonium hexafluorophosphate (6.420 g, 11.96 mmol), <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (2.000 g, 1 1 96 mmol) in DCM (100 mL), was added triethylamine (10.50 mL, 59.82 mmol). The reaction mixture was stirred at rt for 24 h and then concentrated to dryness under vacuum. The crude material was washed with aqueous sodium bicarbonate solution twice, and washed with water twice to give a crude solid. The crude solid was washed with ether twice to yield a white solid (2.673 g, 88.90%) as the title compound. This material was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6) delta 9.1 5 (s, 1 H), 9.1 1 (t, J = 5.8 Hz, 1 H), 8.06 (s, 1 H), 7.73-7.54 (m, 3H), 7.34 (d, J = 4.7 Hz, 4H), 7.28-7.16 (m, 1 H), 4.51 (d, J = 5.9 Hz, 2H). LCMS (ESI): RT = 0.54 min, m/z = 252.2 [M + H]+.

Reference： [1]Patent: WO2013/127266,2013,A1 .Location in patent: Page/Page column 156; 157
[2]Patent: WO2013/127268,2013,A1 .Location in patent: Page/Page column 85

28
[ 1454252-65-3 ]
[ 139022-25-6 ]
[ 1454250-76-0 ]

Yield	Reaction Conditions	Operation in experiment
20%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;	A solution of [5-(benzenesulfonyI)pyrimidin-2- yl]methanamine ( 100 mg, 0.40 mmol, 1 .00 equiv), imidazo[ l ,2-a]pyridine-6- carboxylic acid (78 mg, 0.48 mmol, 1 .20 equiv), EDC1 (230 mg, 1 .48 mmol, 3 69 equiv), triethylamine ( 1 20 mg, 1 . 1 mmol, 2.96 equiv), and HOBt (80 mg, 0.59 mmol, 1 .48 equiv) in DMF (2 mL) was stirred overnight at rt. The reaction mixture was quenched by the addition of 30 mL of water/ice The resulting solution was extracted with 3x30 mL of ethyl acetate The organic layers were combined, washed with 3x30 mL of brine and then dried over anhydrous sodium sulfate. The crude product was purified by Preparative HPLC with the fol lowing conditions (2//-Waters 2767- 2(HPLC-08)) : Column, Xbndge Prep Phenyl, S um, 1 9* 1 50mm, mobi le phase, water with 50 mmol ammonium bicarbonate and acetonitri le ( 1 0.0% acetonitrile up to 33.0% in 2 min, up to 53.0% in 8 min,up to 1 00 0% in 1 min, down to 1 0.0% in 1 min); Detector, UV 220 nm to give 30.8 mg (20%) of the title compound as a white solid. 1HNMR (300 MHz, CD3OD) delta 9.24 (s, 2H), 9.05 (s, 1H), 8.08-8.06 (d, J= 7.5 Hz, 2 H), 7.96 (s, 1 H), 7.75-7.70 (t. J=8.1 Hz, 2H), 7 67-7 60 (m, 4H), 4.90-4.87 (m, 2H), LC/MS (Method J, ESI): RT = 1 .25 min, z = 393.9 [M+H]+

Reference： [1]Patent: WO2013/127267,2013,A1 .Location in patent: Page/Page column 98; 100

29
imidazo[1,2-a]pyridine-6-carboxylic acid hydrochloride [ No CAS ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium hydroxide; In water;pH 5 - 6;	Step 2. Imidazo[ 1 ,2-a]pyridine-6-carboxylic acid hydrochloride salt ( 1 70 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 C using an ice-H20 bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product (107.2 g, 77%) as a light yellow powder. NMR (400 MHz, DMSCW0) delta 1 3.76-1 2.82 (br, 1 H), 9.28 (s, 1 H), 8. 1 0 (s, 1 H), 7.68 (s, 1 H), 7.64-7 56 (m, 2H). MS (ESI+) m z: 163 [M+H]~.
77%	With sodium hydroxide; In water;pH 5 - 6;	Intermediate 2: Imidazo [1,2-al pyridine-6-carboxylic acid [0173] Step 2. Imidazo[1,2-a]pyridine-6-carboxylic acid hydrochloride salt (170 g) was diluted with water (600 mL) and heated until a clear solution resulted, then an aqueous solution of NaOH (2 M) was added slowly to adjust the pH = 5-6. The reaction mixture was cooled to 0 C using an ice-H20 bath. The resulting precipitate was collected by vacuum filtration, then washed with ethanol and dried under vacuum to give the title product (107.2 g, 77%) as a light yellow powder. ?H NMR (400 MHz, DMSO-d6) oe 13.76-12.82 (br, 1H), 9.28 (s, 1H), 8.10 (s, 1H), 7.68 (s, 1H), 7.64-7.56 (m, 2H). MS (ESI+) m/z: 163 [M+H]?.

Reference： [1]Patent: WO2013/127269,2013,A1 .Location in patent: Page/Page column 143
[2]Patent: WO2013/130935,2013,A1 .Location in patent: Paragraph 0173

30
[ 1454285-31-4 ]
[ 139022-25-6 ]
[ 1454284-73-1 ]

Yield	Reaction Conditions	Operation in experiment
10%		Step 6. A solution of <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (76 mg, 0.47 mmol, 1.33 equiv), EDCI (90 mg, 0.47 mmol, 1.33 equiv), HOBt (75 mg, 0.56 mmol, 1.57 equiv), and diisopropylethylamine (500 mg, 3.87 mmol, 10.98 equiv) in DMF (8 mL) was stirred for 10 min at rt. A solution of 3-(4-aminomethyl-benzenesulfonyl)-1-methyl-cyclobutanol (90 mg, 0.35 mmol, 1.00 equiv) in DMF was then added and the resulting solution was stirred overnight at rt. After the reaction completed, the solution was diluted with 100 mL of ethyl acetate and then washed with 100 mL of water. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by Preparative HPLC [Column, Sunfire C18, 19*15; mobile phase, CH3CN:NH4CO3 (10 mmol/L)/H2O = 1 5%-60%, 10 min; Detector, UV 254 nm] to give 14.5 mg (10%) of the title compound as a white solid. LC/MS (Method C, ESI): RT = 1 .33 min, m z = 399.9 [M+H]+ 1H NMR (300 MHz, DMSO-d6) delta 9.23 (t, J = 6.0 Hz, 1 H), 9.17 (s, 1H), 8.08 (s, 1H), 7.78 (m, 2H), 7.66 (m, 5H), 5.36 (s, 1H), 4.60 (d, J = 5.7 Hz, 2H), 3.66 (m, 1H), 2.35 (m, 2H), 2.04 (m, 2H), 1.22 (s, 3H).

Reference： [1]Patent: WO2013/127268,2013,A1 .Location in patent: Page/Page column 80; 82

31
[ 139022-25-6 ]
[ 1454284-94-6 ]

Reference： [1]Patent: WO2013/127268,2013,A1

32
[4-[(R)-(3,5-difluorobenzene)sulfinyl] phenyl]methanamine [ No CAS ]
[ 139022-25-6 ]
(R)-N-[[4-(3,5-difluorophenyl)sulfinylphenyl]methyl]imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%		[0227] Step 5A. (R)-N- [[4-(3 ,5-difluorophenyl)sulfinylphenyll methyll imidazo [1,2- alpyridine-6-carboxamide. A solution of <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (100 mg, 0.62 mmol, 1.50 equiv), EDCI (94.7 mg, 0.49 mmol, 1.20 equiv), HOBt (67 mg, 0.50 mmol,1.20 equiv), and diisopropylethylamine (160 mg, 1.24 mmol, 3.00 equiv) in DMF (10 mL) was stirred at 25 C for 30 mi [4-[(R)-(3,5-Difluorobenzene)sulfinyl]phenyl]methanamine (110 mg, 0.41 mmol, 1.00 equiv) was then added and the resulting solution was stirred for 12 h at 25 C. The reaction mixture was quenched with 50 mL of water. The resulting mixture was extracted with 2x50 mL of dichloromethane. The combined organic layers were washed with lxi 00 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified on a silica gel column eluted with dichloromethane/methanol (100/5) to give 35 mg (2 1%) of the title compound as a white solid. Chiral HPLC, Column: CHIRALPAK AD-H, Column size: 0.46*25 cm, 5 um, Mobile phase: Hexane/EtOH = 50/50 (0.1% TEA), Flow: 1.0 mL/min, Pressure: 5.0 MPa, Detector: UV-254 nm, Temperature: 25C, RT = 11.4 mi LC/MS (Method B, ESI): RT = 1.98 mi m/z = 412.1 [M+Hf?. ?H NMR (400 MHz, CD3OD) oe 9.04 (s, 1H), 7.96 (s, 1H),7.75 (d, J = 8.4 Hz, 2H), 7.71 (s, 1H), 7.66 (s, 1H), 7.59 (m, 3H), 7.35 (d, J = 4.8 Hz, 2H),7.10 (m, 1H), 4.66 (s, 2H). ?9F NMR (400 MHz, CD3OD) oe: -108.1.

Reference： [1]Patent: WO2013/130935,2013,A1 .Location in patent: Paragraph 0227

33
[4-[(S)-(3,5-difluorobenzene)sulfinyl] phenyl]methanamine [ No CAS ]
[ 139022-25-6 ]
(S)-N-[[4-(3,5-difluorophenyl)sulfinylphenyl]methyl]imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%		[0228] Step SB. (S)-N- [[4- (3 ,S-difluorophenyl)sulfinylphenyll methyll imidazo [1,2- alpyridine-6-carboxamide. A solution of imidazo[i,2-a]pyridine-6-carboxylic acid (91 mg, 0.56 mmol, 1.50 equiv), EDCI (86 mg, 0.45 mmol, 1.20 equiv), HOBt (60 mg, 0.44 mmol,1.20 equiv), and diisopropylethylamine (145 mg, 1.12 mmol, 3.00 equiv) in DMF (10 mL) was stirred at 25 C for 30 mi [4-[(S)-(3,S-Difluorobenzene)sulfinyl]phenyl]methanamine (100 mg, 0.37 mmol, 1.00 equiv) was then added and the resulting solution was stirred for 12at 25 C. The resulting solution was diluted with 50 mL of water and then extracted with 2x50 mL of dichloromethane. The combined organic layers were washed with ix 100 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with dichloromethane/methanol (100/5) to give 30.7 mg (20%) of the title compound as a white solid. Chiral HPLC, Column: CHIRALPAK AD-H, Column size: 0.46*25 cm, S um, Mobile phase: Hexane/EtOH = 50/50 (0.1% TEA), Flow:1.0 mL/min, Pressure: 5.0 MPa, Detector: UV-254 nm, Temperature: 25C, RT = 19.2 mm. LC/MS (Method B, ESI): RT = 1.99 mi m/z = 4i2.i[M+H]. ?H NMR (300 MHz, CD3OD)o 9.04 (s, 1H), 7.96 (s, 1H), 7.58 (m, 7H), 7.35 (m, 2H), 7.11 (m, 1H), 4.66 (s, 2H). ?9F NMR (300 MHz, CD3OD) 0: -108.2.

Reference： [1]Patent: WO2013/130935,2013,A1 .Location in patent: Paragraph 0228

34
[ 100-46-9 ]
[ 139022-25-6 ]
imidazo[1,2-a]pyridine-6-carboxylic acid benzylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; at 20℃; for 24h;	[0235] Step 1. Imidazor 2-a1pyridine-6-carboxyric acid benzylamide. To a mixture of benzylamine (2.62 g, 23.9 mmol), (benzotriazol-l-yloxy)tripyrrolidinophosphonium hexafluorophosphate (6.42 g, 11.96 mmol), and imidazo[l,2-a]pyridine-6-carboxylic acid (2.00 g, 11.96 mmol) in methylene chloride (100 mL), was added triethylamine (10.5 mL, 59.8 mmol). The reaction mixture was stirred at room temperature for 24 h and then concentrated to dryness under vacuum. The crude material was washed with an aqueous solution of saturated aqueous sodium bicarbonate twice, water twice and ether twice. The crude white solid was collected by filtration to yield imidazo[l,2-a]pyridine-6-carboxylic acid benzylamide (2.67 g, 89%). This material was used in the next step without further purification. 1H NMR (400 MHz, DMSO-J6) delta 9.15 (s, 1H), 9.11 (t, J = 5.8 Hz, 1H), 8.06 (s, 1H), 7.73-7.54 (m, 3H), 7.34 (d, J = 4.7 Hz, 4H), 7.28-7.16 (m, 1H), 4.51 (d, J = 5.9 Hz, 2H). LC/MS (Method J, ESI): RT = 0.54 min, m/z = 252.2 [M + H]+.

Reference： [1]Patent: WO2013/130943,2013,A1 .Location in patent: Paragraph 0235

35
[ 944325-12-6 ]
[ 139022-25-6 ]
[ 1541193-76-3 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 770 - 792

36
[ 72084-11-8 ]
[ 139022-25-6 ]
[ 1608118-04-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 2118 - 2122

37
[ 1620292-66-1 ]
[ 139022-25-6 ]
[ 1620291-42-0 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of 2?-((3-(aminomethyl)-4,5 -dihydroisoxazol-5-yl)methoxy)- [1,1?- biphenyl]-4-carboxamide hydrochloride (±) (0.150 g, 0.415 mmol) and imidazo[1,2- a]pyridine-6-carboxylic acid (0.100 g, 0.650 mmol) in N,N-dimethylformamide (4.0 mL)added EDCI.HC1 (0.160 g, 0.830 mmol), HOBT (0.112 g, 0.830 mmol) and N,Ndiisopropylethylamine (0.29 mL, 1.660 mmol) at 0 C. The reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with ethyl acetate (100 mL). The organic phase was washed with aqueous sodium bicarbonate solution (50 mL), brine (3x50 mL), dried over sodium sulfate and concentrated under reduced pressure togive a residue. The residue was purified by column chromatography on silica gel (methanolldichloromethane = 0/100 to 4/96) to give the titled compound (0.04 g, 20%) as a solid.HPLC: 97.15%; LCMS:m/z 470.5 [M+H] 1H NMR (400 MHz, Chloroform-d) 8.85 (dd, J= 1.8, 0.9 Hz, 1H), 7.84 -7.74 (m, 2H), 7.73-7.66 (m, 2H), 7.66-7.48 (m, 4H), 7.41 -7.28 (m, 3H), 7.06 (td, J= 7.5, 1.0 Hz, 1H), 6.93 (d, J= 8.2 Hz, 1H), 6.50 (s, 1H), 5.67 (s, 1H), 5.00-4.76 (m, 1H), 4.31 (dd, J= 10.4, 2.5 Hz, 1H), 4.10 (dd, J = 17.0, 5.2 Hz, 1H), 3.96 (dd, J = 10.4, 2.3 Hz, 1H), 3.83 (dd, J = 16.9, 6.1 Hz, 1H), 3.01 (dd, J= 17.1, 11.3 Hz, 1H), 2.82 (dd, J= 17.2, 7.7 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 146; 147

38
[ 1620292-82-1 ]
[ 139022-25-6 ]
[ 1620291-87-3 ]

Yield	Reaction Conditions	Operation in experiment
35%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of (5 -((2-(5-methylpyridin-3-yl)phenoxy)methyl)-4,5 -dihydroisoxazol-3 - yl)methanamine hydrochloride (±) (0.150 g, 0.449 mmol) and imidazo [1 ,2-a]pidine-6 - carboxylic acid (0.110 g, 0.670 mmol) in N,N-dimethylformamide (3 mL) was added EDCI.HC1 (0.170 g, 0.898 mmol) HOBT (0.120 g, 0.898 mmol) and N,N5 diisopropylethylamine (0.31 mL, 1.790 mmol) at 0 C. The reaction mixture was stirredfor 16 h at room temperature. The reaction mixture was diluted with ethyl acetate (250 mL). The organic phase was washed with aqueous sodium bicarbonate solution (50 mL), brine (3 x 50 mL), dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel(methanolldichloromethane = 0/100 to 4/96) to give the titled compound (0.070 g, 35%) as a solid. HPLC: 97.26 %; LCMS: mlz 442.2 [M+H] ?H NMR (400 MHz, Chloroform-d) 9.58 (s, 1H), 9.09 -9.02 (m, 1H), 8.64 (s, 1H), 8.35 (d, J= 2.0 Hz, 1H), 7.87 (dd, J= 9.4, 1.7 Hz, 1H), 7.72-7.55 (m, 4H), 7.40-7.31 (m, 2H), 7.08 (t, J= 7.5 Hz, 1H), 6.92 (d, J= 8.6 Hz, 1H), 5.04-4.89 (m, 1H), 4.46 (dd, J= 16.1, 7.1 Hz, 1H),4.28-4.14 (m, 2H), 4.06 (d, J= 10.2 Hz, 1H), 3.19 (qd, J= 17.6, 9.4 Hz, 2H), 2.42 (s,3H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 190; 191

39
[ 1620292-86-5 ]
[ 139022-25-6 ]
[ 1620291-84-0 ]

Yield	Reaction Conditions	Operation in experiment
30%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 14h;Inert atmosphere;	To a suspension of imidazo [1, 2-a] pidine-6-carboxylic acid (0.079 g, 0.488 mmol)and (5-((2-(2-fluoropyridin-3 -yl) phenoxy) methyl)-4, 5-dihydroisoxazol-3-yl)methanamine dihydrochloride (±) (0.150 g, 0.444 mmol) in N,N-dimethylformamide (4mL) was added EDCI.HC1 (0.102 g, 0.532 mmol), HOBt (0.084 g, 0.621 mmol) andN,N-diisopropylethylamine (0.230 mL, 1.332 mmol) at 0C under nitrogen atmosphere.Reaction mixture was stirred at room temperature for 14 h. The reaction mixture was poured onto ice water, extracted with ethyl acetate (2 x 20 mL). The combined ethyl acetate layer was washed with water, brine solution (2 x 10 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (methanol/dichloromethane =5/95) to give the titled compound (0.060 g, 30%) as a solid. HPLC: 98.98 %; LCMS: m/z 446.1[M+ H] 1H NMR (400 MHz, Chloroform-d) 9.01 (t, J= 1.4 Hz, 1H), 8.24- 8.15 (m,2H), 7.82-7.75 (m, 2H), 7.68 -7.60 (m, 3H), 7.42-7.26 (m, 3H), 7.06 (tt, J= 7.6, 0.6Hz, 1H), 6.90 (d, J= 8.4 Hz, 1H), 4.90 (ddt, J= 11.7, 7.1, 2.2 Hz, 1H), 4.62 (dd, J=16.4, 7.7 Hz, 1H), 4.13 - 4.01 (m, 3H), 3.18 (qd, J = 17.5, 9.4 Hz, 2H). Further the

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 189; 190

40
[ 1620292-86-5 ]
[ 139022-25-6 ]
[ 1620291-85-1 ]
[ 1620291-86-2 ]

Reference： [1]Patent: WO2014/111871,2014,A1

41
(5-((2-(2-methoxypyridin-4-yl)phenoxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine dihydrochioride [ No CAS ]
[ 139022-25-6 ]
[ 1620291-88-4 ]

Yield	Reaction Conditions	Operation in experiment
30%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 14h;Inert atmosphere;	To a suspension of imidazo [1,2-a] pidine-6-carboxylic acid (0.076 g, 0.471 mmol) and (5-((2-(2-methox idin-3 -yl)phenoxy)methyl)-4,5 -dihydroisoxazol-3 -yl)methanamine hydrochloride (±) (0.150 g, 0.428 mmol) in N,N-dimethylfomiamide (4 mL) was added EDCI (0.099 g, 0.514 mmol), HOBt (0.081 g, 0.600 mmol) and N,Ndiisopropylethylamine (0.20 mL, 1.286 mmol) at 0C under nitrogen atmosphere. Thereaction mixture was stirred at room temperature for 14 h. The reaction mixture was poured onto ice water, extracted with ethyl acetate (2 x 20 mL). The combined ethyl acetate layer was washed with water, brine solution (2 x 10 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (methanol/dichloromethane =6/94) togive the titled compound (0.061 g, 30%) as a solid. HPLC: 95.69 %; LCMS: m/z 458.3 [M+ H] 1H NMR (400 MHz, Chloroform-d) 8.89 (dd, J= 1.8, 1.0 Hz, 1H), 8.12 (dd, J= 5.1, 1.9 Hz, 1H), 7.74-7.65 (m, 2H), 7.60 (dd, J= 9.4, 1.8 Hz, 2H), 7.56-7.51 (m,2H), 7.36 (ddd, J= 8.1, 7.4, 1.8 Hz, 1H), 7.07 (td, J= 7.5, 1.0 Hz, 1H), 6.97-6.92 (m,2H), 6.90 (s, 1H), 4.91 (ddt, J= 11.6, 6.1, 3.0 Hz, 1H), 4.31 (dd, J= 17.5, 6.1 Hz, 1H),4.19 (dd, J= 10.2, 3.2 Hz, 1H), 3.98 (dd, J= 10.2,2.8 Hz, 1H), 3.91 (d, J= 0.5 Hz, 3H),3.77 (dd, J= 17.5, 4.7 Hz, 1H), 3.01 (dd, J= 17.0, 11.3 Hz, 1H), 2.82 (dd, J= 17.0, 6.3 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 191; 192

42
(5-((2-(2-methoxypyridin-4-yl)phenoxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine dihydrochioride [ No CAS ]
[ 139022-25-6 ]
[ 1620291-89-5 ]
[ 1620291-90-8 ]

Reference： [1]Patent: WO2014/111871,2014,A1

43
[ 1620292-98-9 ]
[ 139022-25-6 ]
[ 1620291-91-9 ]

Yield	Reaction Conditions	Operation in experiment
49%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	(5-((2-(6-fluoropidin-3-yl)phenoxy)methyl)-4,5 -dihydroisoxazol-3 -yl)methanaminehydrochloride (±) (prepared in step-2 of example- 84) (0.300 g, 0.809 mmol) was reacted with imidazo[1,2-a]pidine-6-carboxylic acid (0.172 g, 1.067 mmol) in the presence ofBOP reagent (0.393 g, 0.889 mmol) and N,N-diisopropylethylamine (0.313 g, 2.427 mmol) in N,N-dimethylformamide (6 mL) at room temperature for 16 h. The reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (50 mL) and washed with water (4 x 50 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified bycolumn chromatography on silica gel (methanolldichloromethane = 3/97) to give titled compound (0.180 g, 49 %) as a solid. LCMS: mlz 446.3 [M+H] HPLC: 97.25 %; ?H NMR (400 MHz, Chloroform-d) 8.99 (dd, J = 2.0, 1.0 Hz, 1H), 8.44 (d, J = 2.4 Hz, 1H), 8.34- 8.28 (m, 1H), 7.91 (td, J= 8.1, 2.5 Hz, 1H), 7.76 -7.61 (m, 4H), 7.40-7.30 (m, 2H), 7.11 -7.03 (m, 2H), 6.96 (d, J= 8.3 Hz, 1H), 4.98 (ddt, J= 11.7, 7.0, 2.3 Hz,1H), 4.40 (dd, J = 16.7, 5.9 Hz, 1H), 4.28 - 4.19 (m, 2H), 4.08 (dd, J = 10.3, 2.1 Hz,1H), 3.22 (dd, J= 17.4, 11.7 Hz, 1H), 3.06 (dd, J= 17.4, 7.0 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 192; 193

44
[ 1620293-20-0 ]
[ 139022-25-6 ]
[ 1620291-60-2 ]

Yield	Reaction Conditions	Operation in experiment
11%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of 2-(4-(2-((3-(aminomethyl)-4,5-dihydroisoxazol-5-yl)methoxy)phenyl)- lH-pyrazol-l-yl)ethanol hydrochloride (±) (0.100 g, 0.284 mmol) and imidazo[l ,2- a]pyridine-6-carboxylic acid (0.070 g, 0.426 mmol) in N,N-dimethylformamide (4 mL) was added EDCI (0.110 g, 0.568 mmol), HOBT (0.077 g, 0.568 mmol) and N,N- diisopropylethylamine (0.2 mL, 1.136 mmol) at 0 C. The reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with ethyl acetate (100 mL). The organic phase was washed with aqueous sodium bicarbonate solution (50 mL), brine (3 x 50 mL), dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (methanol/dichloromethane = 0/100 to 4/96) to give the titled compound (0.015 g, 11 %) as a solid. HPLC: 95.5%: LCMS: m/z 461.1 [M+H] +; 1H NMR (400 MHz, Chloroform- d) delta 8.57 (d, / = 1.3 Hz, 1H), 7.98 (s, 1H), 7.88 (s, 1H), 7.68 (t, / = 5.9 Hz, 1H), 7.65 - 7.56 (m, 2H), 7.56 - 7.35 (m, 3H), 7.25 - 7.14 (m, 1H), 7.00 (t, / = 7.5 Hz, 1H), 6.92 (d, / = 8.4 Hz, 1H), 5.13 - 4.94 (m, 1H), 4.42 (dd, / = 16.1, 6.3 Hz, 1H), 4.37 - 4.26 (m, 4H), 4.26 - 4.14 (m, 2H), 4.09 (dt, / = 11.5, 4.5 Hz, 2H), 3.31 - 3.02 (m, 2H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 166; 167

45
[ 1620293-34-6 ]
[ 139022-25-6 ]
[ 1620291-74-8 ]

Yield	Reaction Conditions	Operation in experiment
35%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	(5-((2-(iH-pyrazol-l-yl)phenoxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (prepared in step-6 of example-98) (0.100 g, 0.323 mmol) was reacted with imidazo[l ,2-a]pyridine-6-carboxylic acid (0.062 g, 0.388 mmol) in the presence of BOP reagent (0.171g, O.388mmol) and N,N-diisopropylethylamine (0.168 mL, 0.969 mmol) in N,N-dimethylformamide (3 mL) at room temperature for 16h. The reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (30 mL) and washed with water (4 x 30 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by combifiash column chromatography (methanol/dichloromethane = 4/96) to give titled compound (0.048 g, 35%) as a solid. LCMS: m/z 417.1 [Mu+Eta] +; HPLC: 92.30 %; H NMR (600 MHz, DMSO-d6) delta 9.15 (t, / = 1.4 Hz, 1H), 8.99 (t, / = 5.7 Hz, 1H), 8.22 (d, / = 2.5 Hz, 1H), 8.12 - 8.07 (m, lH), 7.72 - 7.61 (m, 5H), 7.34 (ddd, / = 9.0, 7.4, 1.7 Hz, 1H), 7.26 (dd, / = 8.4, 1.3 Hz, 1H), 7.14 - 7.07 (m, 1H), 6.50 (t, / = 2.1 Hz, 1H), 4.94 (dp, / = 10.7, 3.5 Hz, 1H), 4.24 - 4.20 (m, 3H), 4.13 (dd, / = 10.5, 5.9 Hz, 1H), 3.23 - 3.14 (m, 1H), 2.90 (dd, / = 17.6, 7.4 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 182

46
[ 1620293-40-4 ]
[ 139022-25-6 ]
[ 1620291-73-7 ]

Yield	Reaction Conditions	Operation in experiment
8%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of (5-((2-(lH-pyrrol-l -yl) phenoxy) methyl)-4, 5-dihydroisoxazol-3-yl) methanamine hydrochloride (±) (0.240 g, 0.880 mmol) and imidazo[l ,2-a]pyridine-6- carboxylic acid (0.216 g, 1.320 mmol) in N,N-dimethylformamide (4 mL) was added EDCI (0.340 g, 1.760 mmol), HOBT (0.240 g, 1.760 mmol) and N,N- diisopropylethylamine (0.460 mL, 2.640 mmol) at 0 C. The reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with ethyl acetate (100 mL). The organic phase was washed with aqueous sodium bicarbonate solution (50 mL), brine (3x50 mL), dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (methanol/dichloromethane = 0/100 to 4/96) to give the titled compound (0.030 g, 8 %) as a solid. HPLC: 99.8 %; LCMS : m/z 416.4 [M+H] +; lU NMR (400 MHz, Chloroform-d) delta 8.65 (dd, / = 1.8, 1.0 Hz, 1H), 7.71 (d, / = 1.3 Hz, 1H), 7.67 - 7.56 (m, 2H), 7.35 (dd, / = 9.4, 1.8 Hz, 1H), 7.32 - 7.28 (m, 2H), 7.28 - 7.22 (m, 2H), 7.10 - 6.95 (m, 2H), 6.31 (t, / = 2.2 Hz, 2H), 6.23 (s, 1H). 4.99 (d, / = 8.8 Hz, 1H), 4.50 (dd, / = 16.5, 6.9 Hz, 1H), 4.39 - 4.23 (m, 1H), 4.17 (dd, / = 16.1, 4.2 Hz, 1H), 4.06 - 3.86 (m, 1H), 3.12 (dd, / = 17.3, 11.7 Hz, 1H), 3.02 - 2.80 (m, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 181; 182

47
[ 1620293-48-2 ]
[ 139022-25-6 ]
[ 1620292-09-2 ]

Yield	Reaction Conditions	Operation in experiment
15%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	(5-((3-morpholinophenoxy)methyl)-4,5 -dihydroisoxazol-3-yl)methanaminehydrochloride (±) (0.130 g, 0.396 mmol) was reacted with imidazo[1,2-a]pyridine-6- carboxylic acid (0.077 g, 0.475 mmol) in the presence of BOP reagent (0.192 g, 0.435mmol) and N,N-diisopropylethylamine (0.153g, 1.188 mmol) in N,N-dimethyl formamide (3 mL) at room temperature for 16h. The reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (30 mL) and washed with water (4 x 30 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC to give titledcompound (0.025 g, 15 %) as a solid. LCMS: m/z 436.2 [M+H] HPLC: 98.37 %; 1HNMR (400 MHz, DMSO-d6) 9.14 (t, J= 1.3 Hz, 1H), 9.01 (t, J= 5.7 Hz, 1H), 8.09-8.06 (m, 1H), 7.70 - 7.60 (m, 3H), 7.09 (t, J = 8.2 Hz, 1H), 6.52 (dd, J = 8.2, 2.3 Hz,1H), 6.45 (t, J= 2.3 Hz, 1H), 6.41 -6.35 (m, 1H), 4.86 (ddd, J= 11.0, 6.8, 4.1 Hz, 1H),4.25 (d, J= 5.7 Hz, 2H), 3.99 (qd, J= 10.5, 4.9 Hz, 2H), 3.69 (dd, J= 5.9, 3.8 Hz, 4H),3.18 (dd, J= 17.5, 10.9 Hz, 1H), 3.06 (t, J= 4.8 Hz, 4H), 2.90 (dd, J= 17.4,7.3 Hz, 1H). PREPARATIVE HPLC PURIFICATION METHOD:COLUMN: XDB-C18 (21.20 x 150mm, 5 micron); MOBILE PHASE: (A): 0.1% TFA in Water; (B): acetonitrile.FLOW RATE: 20.0 mllmin

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 217; 218

48
[ 1620293-78-8 ]
[ 139022-25-6 ]
[ 1620293-80-2 ]

Yield	Reaction Conditions	Operation in experiment
55%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 16h;	General procedure: To a solution of (5-(([ 1,1? -biphenyl] -2-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (prepared in step-4 of example-i) (0.200 g, 0.627 mmol)and i-tosyl-iH-pyrrolo[3,2-c]pyridine-2-carboxylic acid (0.298 g, 0.942 mmol) in N,N5 dimethylformamide (5 mL) was added of EDCI.HC1 (0.24i g, i .258 mmol), HOBt(0.i70 g, i.258 mmol) and N,N-diisopropylethylamine (0.440 mL,2.500 mmol) at room temperature. The reaction mixture was stirred for i 6 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate (2 x 50 mL) and washed with water (2 x 50 mL). The organic phase was dried over sodium sulfate andconcentrated under reduced pressure to give the titled compound (0.200 g, 72.9 %) as crude. The crude product was taken to the next step without further purification. (5-((2-bromophenoxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine (±) (0.600 g, 2.104 mmol) was reacted with imidazo[l,2-a]pyridine-6-carboxylic acid (0.375 g, 2.314 mmol) in the presence of EDCI.HC1 (0.605 g, 3.156 mmol), HOBt (0.014 mg, 0.105 mmol) and triethylamine (0.873 mL, 6.313 mmol) in dichloromethane (10 mL) as described in the synthesis of step-2 of example- 110 to give the titled compound (0.500 g, 55%) as a solid. LCMS: m/z 430.95 [M+2] +; H NMR (300 MHz, DMSO-d6) delta 9.15 (s, 1H), 9.01 (d, / = 6.3 Hz, 1H), 8.08 (s, lH), 7.72 - 7.59 (m, 3H), 7.55 (d, / = 7.9 Hz, 1H), 7.33 (t, / = 8.0 Hz, 1H), 7.11 (d, / = 8.3 Hz, 1H), 6.89 (t, / = 7.8 Hz, 1H), 4.92 (d, / = 10.1 Hz, 1H), 4.27 (d, / = 5.7 Hz, 2H), 4.21 - 4.03 (m, 2H), 3.21 (dd, / = 17.6, 11.0 Hz, 1H), 3.01 (dd, / = 17.6, 7.2 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 137; 157

49
[ 1620293-68-6 ]
[ 139022-25-6 ]
[ 1620293-70-0 ]

Yield	Reaction Conditions	Operation in experiment
35%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 16h;	General procedure: To a solution of (5-(([ 1,1? -biphenyl] -2-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (prepared in step-4 of example-i) (0.200 g, 0.627 mmol)and i-tosyl-iH-pyrrolo[3,2-c]pyridine-2-carboxylic acid (0.298 g, 0.942 mmol) in N,N5 dimethylformamide (5 mL) was added of EDCI.HC1 (0.24i g, i .258 mmol), HOBt(0.i70 g, i.258 mmol) and N,N-diisopropylethylamine (0.440 mL,2.500 mmol) at room temperature. The reaction mixture was stirred for i 6 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate (2 x 50 mL) and washed with water (2 x 50 mL). The organic phase was dried over sodium sulfate andconcentrated under reduced pressure to give the titled compound (0.200 g, 72.9 %) as crude. The crude product was taken to the next step without further purification. 4-((3-(aminomethyl)-4,5-dihydroisoxazol-5 -yl)methoxy)-3 -bromobenzonitrilehydrochloride (±) (0.400 g, 1.290 mmol) was reacted with imidazo[i ,2-a]pidine-6- carboxylic acid (0.250 g, 1.550 mmol) in the presence of HATU (0.736g, 1.93Ommol)and N,N-diisopropylethylamine (0.600 mL, 3.23Ommol) in N,N-dimethylformamide (10 mL) as described in the synthesis of step-2 of example-i 10 to give the titled compound (0.200 g, 35%) as a solid. LCMS: mlz 454.0 [M+H] ?H NMR (300 MHz, Chloroformd) 8.82 (d, J= 1.5 Hz, 1H), 8.18 (t, J= 5.7 Hz, 1H), 7.75 (d, J= 2.0 Hz, 1H), 7.65 (d, J = 1.4 Hz, 1H), 7.61 -7.49 (m, 4H), 6.91 (d, J= 8.6 Hz, 1H), 4.98 (ddt, J= 10.8, 7.3, 3.8Hz, 1H), 4.18 (dd, J= 10.3, 3.8 Hz, 2H), 4.12 -4.00 (m, 2H), 3.27-3.09 (m, 2H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 137; 151; 152; 153

50
[ 1620293-96-0 ]
[ 139022-25-6 ]
[ 1620291-59-9 ]

Yield	Reaction Conditions	Operation in experiment
8%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	(5-(((l-methyl-iH-indazol-4-yl)oxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (0.080 g, 0.269 mmol) was reacted with imidazo[l ,2-a]pyridine-6- carboxylic acid (0.052 g, 0.323 mmol) in the presence of BOP reagent (0.130 g, 0.295 mmol) and Nu,Nu-diisopropylethylamine (0.14 mL, 0.807 mmol) in Nu,Nu- dimethylformamide (3 mL) at room temperature for 16 h. The reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (30 mL) and washed with water (4 x 30 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (methanol/dichloromethane = 3/97) to give titled compound (0.012 g, 8.0 %) as a solid. LCMS: m/z 405.3 [Mu+Eta] +; HPLC: 88.52 %; 1H NMR (400 MHz, DMSO-d6) 5 9.15 (t, / = 1.4 Hz, 1H), 9.04 (t, / = 5.8 Hz, 1H), 8.10 - 8.06 (m, 1H), 7.99 (d, / = 0.9 Hz, 1H), 7.69 - 7.60 (m, 3H), 7.30 - 7.25 (m, 1H), 7.17 (d, / = 8.4 Hz, 1H), 6.57 (d, / = 7.6 Hz, 1H), 5.02 - 4.92 (m, 1H), 4.30 - 4.14 (m, 4H), 3.99 (s, 3H), 3.25 - 3.19 (m, 1H), 3.00 (dd, / = 17.5, 7.2 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 165; 166

51
[ 1620294-01-0 ]
[ 139022-25-6 ]
[ 1620294-03-2 ]

Yield	Reaction Conditions	Operation in experiment
62%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	(5-((3-bromophenoxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (0.300 g, 0.932 mmol) was reacted with imidazo[l,2-a]pyridine-6-carboxylic acid (0.181 g, 1.119 mmol) in the presence of BOP reagent (0.452 g, 1.025 mmol) and Nu,Nu- diisopropylethylamine (0.359 g, 2.790 mmol) in Nu,Nu-dimethylformamide (10 mL) at room temperature for 16 h. The reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (50 mL) and washed with water (4 x 50 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (methanol/dichloromethane = 2/98) to give titled compound (0.250 g, 62 %) as a solid. LCMS: m/z 429.3 [M+H] +; lU NMR (300 MHz, Chloroform-d) delta 8.83 (m, 1H), 7.73 - 7.62 (m, 3H), 7.44 (dd, / = 9.4, 1.8 Hz, 1H), 7.15 - 7.04 (m, 2H), 6.90 - 6.79 (m, 2H), 5.07 - 4.98 (m, 1H), 4.43 (d, / = 5.3 Hz, 2H), 4.06 (d, / = 4.7 Hz, 2H), 3.25 (dd, / = 17.3, 10.7 Hz, 1H), 3.09 (dd, / = 17.3, 7.2 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 168; 169; 170

52
[ 1620294-09-8 ]
[ 139022-25-6 ]
[ 1620291-68-0 ]

Yield	Reaction Conditions	Operation in experiment
0.025 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 14h;Inert atmosphere;	To a stirred solution of imidazo [1, 2-a] pyridine-6-carboxylic acid (0.048 g, 0.296 mmol) and (5-(l-(2-(l-methyl-lH-pyrazol-4-yl) phenoxy) ethyl)-4, 5-dihydroisoxazol-3- yl) methanamine hydrochloride (±) (0.100 g, 0.296 mmol) in N,N-dimethylformamide (5.0 mL) was added EDCI.HC1 (0.063 g, 0.326 mmol), HOBt (0.052 g, 0.385 mmol) and triethylamine (0.123 mL, 0.890 mmol) at 0C under nitrogen atmosphere. Reaction mixture was stirred at room temperature for 14 h. The reaction mixture was poured onto ice water, extracted with ethyl acetate (2 x 20 mL) and washed with water (2 x 10 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (methanol/dichloromethane = 6/94) to give the titled compound (0.025g, 19%) as a solid. HPLC: 96.53 %; LCMS: m/z 445.0 [M+H] +; H NMR (400 MHz, Chloroform-d) delta 8.91 (s, 1H), 8.69 (s, 1H), 7.89 - 7.59 (m, 5H), 7.42 - 7.38 (m, 2H), 7.23 - 7.19 (m, 1H), 7.10 - 6.94 (m, 2H), 4.85 - 4.45 (m, 2H), 4.19 - 4.16 (m, 2H), 3.95 - 3.92 (m, 3H), 3.18 - 3.07(m, lH), 2.89 - 2.80 (m, 1H), 1.56 - 1.35 (m, 3H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 174; 175; 176

53
[ 1620294-13-4 ]
[ 139022-25-6 ]
[ 1620291-69-1 ]

Yield	Reaction Conditions	Operation in experiment
15%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	(5-((2-(lH-pyrazol-5-yl) phenoxy) methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (0.120 g, 0.389 mmol) was reacted with imidazo[l ,2-a]pyridine-6- carboxylic acid (0.075 g, 0.467 mmol) in the presence of BOP reagent (0.189 g, 0.427 mmol) and Nu,Nu-diisopropylethylamine (0.337 mL, 1.945 mmol) in Nu,Nu- dimethylformamide (5 mL) at room temperature for 16 h. The reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (50 mL) and washed with water (4 x 50 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (methanol/dichloromethane = 2.5/97.5) to give the titled compound (0.025 g, 15 %) as a sticky solid. LCMS: m z 417.3 [M+H] +; HPLC: 95.95 %; H NMR (400 MHz, DMSO-d6) delta 12.82 (d, / = 13.5 Hz, 1H), 9.08 (s, 1H), 8.94 (d, / = 5.5 Hz, 1H), 8.05 - 8.00 (m, 1H), 7.88(s, 1H), 7.72 - 7.56 (m, 4H), 7.22 (s, lH), 7.04 (dd, / = 42.6, 16.8 Hz, 2H), 6.70 (d, / = 21.8 Hz, 1H), 4.95 (s, 1H), 4.22 - 4.02 (m, 4H), 3.15 (dd, / = 13.4, 4.3 Hz, lH), 2.90 (dd, / = 17.5, 7.2 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 176; 177

54
[ 139022-25-6 ]
[ 1620291-62-4 ]

Reference： [1]Patent: WO2014/111871,2014,A1

55
(5-((2-(2-methoxypyridin-4-yl)phenoxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine dihydrochloride [ No CAS ]
[ 139022-25-6 ]
[ 1620291-82-8 ]

Yield	Reaction Conditions	Operation in experiment
42%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 1.5h;Inert atmosphere;	To a suspension of imidazo[i,2-a] pidine-6-carboxylic acid (0.076 g, 0.471 mmol) and (5-((2-(2-methox idin-4-yl) phenoxy) methyl)-4, 5-dihydroisoxazol-3-yl) methanamine dihydrochloride (±) (0.150 g, 0.428 mmol) in N,N-dimethylformamide (4 mL) was added EDCI.HC1 (0.099 g, 0.5 14 mmol), HOBt (0.081 g, 0.600 mmol) andN,N-diisopropylethylamine (0.200 mL, 1.286 mmol) at 0C under nitrogen atmosphere. Reaction mixture was stirred at room temperature for 1.5 h. The reaction mixture was poured onto ice water, extracted with ethyl acetate (2 x 20 mL). The combined ethyl acetate layer was washed with water, brine solution (2 x 10 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. Theresidue was purified by column chromatography (methanolldichloromethane = 6/94) to give the titled compound (0.080 g, 42%) as a solid. HPLC: 96.59 %; LCMS: m/z 458.2 [M+ H] 1H NMR (400 MHz, Chloroform-d) 8.80 (dt, J= 1.6, 0.8 Hz, 1H), 8.20- 8.17 (m, 1H), 7.74 - 7.63 (m, 3H), 7.44 - 7.31 (m, 3H), 7.12 - 7.06 (m, 2H), 6.99 - 6.90 (m, 2H), 6.62 - 6.54 (m, 1H),4.97 (ddd, J = 10.7, 7.0, 3.4 Hz, 1H), 4.36 - 4.15 (m, 3H),4.09-4.02 (m, 1H),3.94(s,3H), 3.12 (dd, J= 17.2, 11.3 Hz, 1H), 2.97 (dd, J= 17.2, 7.2 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 188; 189

56
[ 1620294-33-8 ]
[ 139022-25-6 ]
[ 1620291-95-3 ]
[ 1620291-96-4 ]

Yield	Reaction Conditions	Operation in experiment
0.020 g; 0.10 g		To a solution of tert-butyl((5 -((2-(6-(benzyloxy)pidin-3 -yl)phenoxy)methyl)-4,5 -dihydroisoxazol-3-yl)methyl) carbamate (±) (0.500 g, i.02i mmol) in diethyl ether (20mL) was added ethereal HC1 (20 mL) at 0C under inert atmosphere, and then stirred fori2 h at room temperature. Then reaction mixture concentrated under reduced pressure togive solid. This solid was triturated with dry diethyl ether (2 x iO mL) to give the mixture of titled compound 2a & 2b as crude compound (0.300 g, 69%) as solid.2a: LCMS: m/z 390.i [M+ H] ÷ (Free base). To a solution of (5-(([ 1,1? -biphenyl] -2-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (prepared in step-4 of example-i) (0.200 g, 0.627 mmol)and i-tosyl-iH-pyrrolo[3,2-c]pyridine-2-carboxylic acid (0.298 g, 0.942 mmol) in N,N5 dimethylformamide (5 mL) was added of EDCI.HC1 (0.24i g, i .258 mmol), HOBt(0.i70 g, i.258 mmol) and N,N-diisopropylethylamine (0.440 mL,2.500 mmol) at room temperature. The reaction mixture was stirred for i 6 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate (2 x 50 mL) and washed with water (2 x 50 mL). The organic phase was dried over sodium sulfate andconcentrated under reduced pressure to give the titled compound (0.200 g, 72.9 %) as crude. The crude product was taken to the next step without further purification.The crude mixture of 2a & 2b (0.350 g, 0.822 mmol) was reacted with imidazo[1,2- a]pyridine-6-carboxylic acid (0.199 g, 1.232 mmol) in the presence of EDCI.HC1(0.316g, 1.643mmo1), HOBt (0.222 g, 1.643 mmol) and N,N-diisopropylethylamine (0.59 mL,3.287 mmol) in N,N-dimethylformamide (5 mL) as described in the synthesis of step-2 of example-i 10. The crude was separated by column chromatography to give the titled compound 3a (0.020g) and 3b (0.100 g) as a solid. 3a(Example-164): LCMS: mlz 534.2 [M+H] HPLC: 95.26%; ?H NMR (400 MHz,DMSO-d6) E9.13 (s,1H), 8.94 (t, J= 5.6 Hz, 1H), 8.31 (t, J= 1.8 Hz, 1H), 8.06 (d, J=1.3 Hz, 1H), 7.90 (dt, J = 8.6, 1.9 Hz, 1H), 7.68 - 7.57 (m, 3H), 7.49 - 7.42 (m, 2H),7.41 -7.27 (m, 5H), 7.13 (d, J= 8.2 Hz, 1H), 7.05 (t, J= 7.5 Hz, 1H), 6.92 (dd, J= 8.6,1.3 Hz, 1H), 5.38 (d, J = 1.4 Hz, 2H), 4.86 (dt, J = 10.4, 4.9 Hz, 1H), 4.24 - 3.96 (m,4H), 3.22-3.08 (m, 1H), 2.86 (dd, J= 17.2, 7.1 Hz, 1H).3b(Example-165): LCMS: mlz 444.2 [M+H] HPLC: 97.97%; ?H NMR (400 MHz,DMSO-d6) 11.73 (s, 1H),9.14 (d, J= 1.4 Hz, 1H), 8.97 (t, J= 5.8 Hz, 1H), 8.08 (s,1H), 7.65 (ddd, J= 11.5, 6.0, 2.4 Hz, 4H), 7.50 (d, J= 2.7 Hz, 1H), 7.40 -7.20 (m, 2H),7.11 -6.92 (m, 2H), 6.36 (d, J= 9.5 Hz, 1H), 4.87 (dq, J= 14.5, 5.5 Hz, 1H), 4.19 (d, J= 5.5 Hz, 2H), 4.07 (qd, J = 10.4, 4.6 Hz, 2H), 3.22 - 3.09 (m, 2H), 2.87 (dd, J = 17.5,7.6 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 196; 197

57
[ 1620294-54-3 ]
[ 139022-25-6 ]
[ 1620292-00-3 ]

Yield	Reaction Conditions	Operation in experiment
0.034 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 14h;Inert atmosphere;	To a suspension of (5-((2-(pidin-2-yl) phenoxy) methyl)-4, 5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (0.075 g, 0.234 mmol) in N,N-dimethylformamide (2mL) was added imidazo[1,2-a]pidine-6-carboxylic acid (0.038 g, 0.234 mmol), EDCI(0.049 g, 0.258 mmol), HOBt (0.041 g, 0.304 mmol) and triethylamine (0.098 mL, 0.703mmol) at 0C under nitrogen atmosphere. Reaction mixture was stirred at roomtemperature for 14 h. The reaction mixture was poured onto ice water, extracted with ethyl acetate (2 x 20 mL). The combined ethyl acetate was washed with water, brine solution (2 x 10 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by combi flashcolumn chromatography (methanolldichloromethane = 6/94) to give the titled compound(0.034 g, 34%) as a solid. HPLC: 95.12%; LCMS: m/z 428.1 [M+H] 1H NMR (600MHz, Chloroform-d) 8.71 -8.64 (m, 2H), 7.78-7.67 (m, 3H), 7.64 (dd, J= 7.6, 1.8Hz, 1H), 7.61 -7.55 (m, 2H), 7.42 (dd, J= 9.5, 1.8 Hz, 1H), 7.36 (ddd, J= 8.9, 7.5, 1.8Hz, 1H), 7.24 (td, J= 4.9, 2.5 Hz, 1H), 7.13 (bs, 1H), 7.07 (td, J= 7.5, 1.0 Hz, 1H), 6.99(d, J= 8.2 Hz, 1H), 4.96 (ddt, J= 11.6, 6.0, 3.0 Hz, 1H), 4.42 (dd, J= 16.3, 6.7 Hz, 1H),4.22-4.06 (m, 3H), 3.09 (dd, J= 17.2, 11.2 Hz, 1H), 2.93 (dd, J= 17.2, 5.9 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 203; 204

58
[ 1620294-60-1 ]
[ 139022-25-6 ]
[ 1620292-01-4 ]

Yield	Reaction Conditions	Operation in experiment
17%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere;	(5-((2-(5 -fluoropidin-2-yl)phenoxy)methyl)-4,5 -dihydroisoxazol-3 -yl)methanaminehydrochloride (±) (0.060 g, 0.177 mmol) was reacted with imidazo[1,2-a]pidine-6- carboxylic acid (0.037 g, 0.230 mmol) in the presence of BOP reagent (0.093 g, 0.212 mmol) and N,N-diisopropylethylamine (0.068 g, 0.53 1 mmol) in N,Ndimethylformamide (3 mL) at room temperature for 16 h. The reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (30 mL) and washed with water(4 x 30 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by combiflash column chromatography (methanolldichloromethane = 4/96) to give titled compound (0.014 g, 17%) as a solid. LCMS: mlz 446.1 [M+H] HPLC: 97.65 %; ?H NMR (400 MHz, DMSO-d6) 9.13 (t, J= 1.4 Hz, 1H), 8.97 (t, J= 5.8 Hz, 1H), 8.63 (d, J= 3.0 Hz, 1H),8.13 - 8.07 (m, 1H), 7.96 (dd, J= 8.9, 4.6 Hz, 1H), 7.81 -7.71 (m, 2H), 7.70-7.60 (m,3H), 7.40 (ddd, J= 8.9, 7.5, 1.8 Hz, 1H), 7.16 (d, J= 8.2 Hz, 1H), 7.08 (t, J= 7.5 Hz,1H), 4.91 (dq, J = 11.0, 5.0 Hz, 1H), 4.21 - 4.16 (m, 3H), 4.12 (dd, J = 10.6, 5.6 Hz,1H), 3.22-3.11 (m, 1H), 2.90 (dd, J= 17.5, 7.7 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 204; 206

59
[ 1620294-64-5 ]
[ 139022-25-6 ]
[ 1620292-04-7 ]

Yield	Reaction Conditions	Operation in experiment
10%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	5 -(2-((3 -(aminomethyl)-4,5 -dihydroisoxazol-5 -yl)methoxy)phenyl)- i -methylpyridin2(111)-one hydrochloride (±) (0.060 g, 0.i7i mmol) was reacted with imidazo[i,2- a]pyridine-6-carboxylic acid (0.036 g, 0.222 mmol) in the presence of BOP reagent (0.093 g, 0.205 mmol) and N,N-diisopropylethylamine (0.066 g, 0.5i3 mmol) in DMF (3mL) at room temperature for i6 h. The reaction mixture was diluted with water (iO mL) extracted with ethyl acetate (30 mL) and washed with water (4 x 30 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by combiflash column chromatography (methanolldichloromethane = 4/96) to give the titled compound (0.008 g, iO%) as asolid. LCMS: mlz 458.i [M+H] HPLC: 97.80 %; ?H NMR (400 MHz, DMSO-d6)9.i3 (t, J= i.4 Hz, iH), 8.96 (t, J= 5.7 Hz, iH), 8.08 (d, J= i.3 Hz, iH), 7.89 (d, J=2.6 Hz, iH), 7.7i -7.58 (m, 4H), 7.37 - 7.24 (m, 2H), 7.09 (d, J = 8.2 Hz, iH), 7.02 (t, J= 7.5 Hz, iH), 6.4i (d, J = 9.4 Hz, iH), 4.95 - 4.8i (m, iH), 4.i8 (d, J = 5.7 Hz, 2H),4.08 (qd, J= iO.5, 4.8 Hz, 2H), 3.48 (s, 3H), 3.i6 (dd, J= i7.5, iO.8 Hz, iH), 2.88 (dd, J= i7.5, 7.6 Hz, iH).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 208; 209

60
[ 1620294-70-3 ]
[ 139022-25-6 ]
[ 1620292-05-8 ]

Yield	Reaction Conditions	Operation in experiment
40%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of (5-((2-(4-methylpiperazin-1-yl) phenoxy) methyl)-4, 5-dihydroisoxazol-3-yl) methanamine hydrochloride (±) (0.150 g, 0.440 mmol) and <strong>[139022-25-6]imidazo[1,2-a]pyridine-6-carboxylic acid</strong> (0.107 g, 0.660 mmol) in N,N-dimethylformamide (4 mL) was addedEDCI.HC1 (0.170 g, 0.880 mmol), HOBT (0.120 g, 0.880 mmol) and N,Ndiisopropylethylamine (0.300 mL, 1.760 mmol) at 0 C. The reaction mixture was stirredfor 16 h at room temperature. The reaction mixture was diluted with ethyl acetate (250 mL). The organic phase was washed with aqueous sodium bicarbonate solution (50 mL), brine (3 x 50 mL), dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (methanolldichloromethane = 0/100 to 4/96) to give the titled compound (0.080 g, 40 %) as a solid. HPLC: 91.6 %; LCMS: m/z 449.2 [M+H] ?H NMR (400 MHz, Chloroformd) 8.83 (dd, J= 1.8, 1.0 Hz, 1H), 7.70 (d, J= 1.3 Hz, 1H), 7.66 (dd, J= 1.3, 0.7 Hz,1H), 7.60 (dt, J= 9.5, 0.8 Hz, 1H), 7.49 (dd, J= 9.5, 1.8 Hz, 1H), 7.09 (td, J= 7.7, 1.7Hz, 1H), 7.05 - 6.96 (m, 2H), 6.92 (dt, J = 8.0, 1.6 Hz, 2H), 5.04 (tt, J = 9.6, 3.0 Hz,1H), 4.65 (dd, J= 17.3, 6.2 Hz, 1H), 4.36 (dd, J= 17.3, 5.0 Hz, 1H), 4.26 (dd, J= 10.4,3.0 Hz, 1H), 4.22-4.01 (m, 3H), 3.95 (d, J= 13.7 Hz, 1H), 3.65 -3.52 (m, 2H), 3.31(dd, J= 10.9, 2.5 Hz, 2H), 3.28 -3.22 (m, 2H), 3.18 (s, 3H), 2.99-2.86 (m, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 209; 211

61
[ 1620294-76-9 ]
[ 139022-25-6 ]
[ 1620292-07-0 ]

Yield	Reaction Conditions	Operation in experiment
40%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of (5-((2-(piperidin-1-yl) phenoxy) methyl)-4, 5-dihydroisoxazol-3-yl) methanamine hydrochloride (±) (0.150 g, 0.476 mmol) and imidazo[1,2-a]pidine-6-carboxylic acid (0.116 g, 0.710 mmol) in N,N-dimethylformamide (4 mL) added EDCI (0.180 g, 0.950 mmol), HOBT (0.130 g, 0.950 mmol) and N,N-diisopropylethylamine (0.330 mL, 1.900 mmol) at 0 C. The reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with ethyl acetate (250 mL). The organic phase was washed with aqueous sodium bicarbonate solution (50 mL), brine (3 x 50 mL),dried over sodium sulfate and concentrated under reduced pressure to give a residue. Theresidue was purified by column chromatography on silica gel (methanolldichloromethane= 0/100 to 4/96) to give the titled compound (0.08 g, 40 %) as a solid. HPLC: 95.2 %;LCMS: m/z 434.5 [M+H] ?H NMR (400 MHz, Chloroform-d) 8.45 (s, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.63 (a, J= 1.3 Hz, 1H), 7.46 (a, J= 9.4 Hz, 1H), 7.36 (dd, J= 9.4, 1.8Hz, 1H), 7.15-7.10 (m, 1H), 7.10-6.88 (m, 4H), 5.09 (ddt, J= 10.4, 5.0, 2.8 Hz, 1H),4.81 (dd, J= 15.5, 8.0 Hz, 1H), 4.32 (dd, J= 15.3, 2.5 Hz, 1H), 4.15 (d, J= 2.8 Hz, 2H),3.26 (dd, J = 16.8, 10.6 Hz, 1H), 3.19 - 3.06 (m, 3H), 2.56 (dd, J = 10.2, 6.6 Hz, 2H),1.83- 1.66 (m, 3H), 1.53 (q, J= 5.6 Hz, 3H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 212; 214; 215

62
[ 1620294-81-6 ]
[ 139022-25-6 ]
[ 1620292-08-1 ]

Yield	Reaction Conditions	Operation in experiment
0.025 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 14h;Inert atmosphere;	To a suspension of imidazo[1,2-a]pidine-6-carboxylic acid (0.089 g, 0.549 mmol), (5-((2-morpholinophenoxy) methyl)-4,5-dihydroisoxazol-3-yl) methanamine hydrochloride(±) (0.200 g, 0.549 mmol) in N,N-dimethylformamide (5.0 mL) was added EDCI.HC1 (0.127 g, 0.658 mmol), HOBt (0.111 g, 0.823 mmol) and N,N-diisopropylethylamine (0.212 mL, 1.647 mmol) at 0 C under nitrogen atmosphere. Reaction mixture was stirred at room temperature for 14 h. The reaction mixture was poured onto ice water,extracted with ethyl acetate (2 x 20 mL). The combined ethyl acetate layer was washed with water, brine solution (2 x 10 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC method to give the titled compound (0.025 g, 21.1 %) as solid. HPLC:99.33%; LCMS: mlz 436.4 [M+H] 1H NMR (400 MHz, Chloroform-d) 8.59 (s, 1H),7.68-7.64 (m, 1H), 7.47 (d, J= 9.4 Hz, 1H), 7.40 (s, 1H), 7.32 (d, J= 10.1 Hz, 2H),7.06 (dt, J= 20.3, 7.5 Hz, 2H), 6.93 (dd, J= 16.3, 8.0 Hz, 2H), 5.12-5.07 (m, 1H), 4.69(dd, J= 15.8, 7.2 Hz, 1H), 4.41 -4.31 (m, 1H), 4.15 (s, 2H), 3.88 - 3.72 (m, 4H), 3.25(dt, J= 20.1, 10.3 Hz, 3H), 3.11 (dd, J= 17.0, 5.4 Hz, 1H), 2.75 (d, J= 10.3 Hz, 2H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 215; 217

63
[ 1620294-96-3 ]
[ 139022-25-6 ]
[ 1620292-12-7 ]

Yield	Reaction Conditions	Operation in experiment
0.025 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 14h;Inert atmosphere;	To a suspension of imidazo [1, 2-a] pidine-6-carboxylic acid (0.058 g, 0.360 mmol)and (5-((4-chlorophenoxy) methyl)-4,5-dihydroisoxazol-3-yl)methanaminehydrochloride (±) (0.iOOg, 0.360 mmol) in N,N-dimethylformamide (2.0 mL) was addedEDCI (0.083 g, 0.432 mmol), HOBt (0.073 g, 0.541 mmol) and N,Ndiisopropylethylamine (0.123 mL, 1.082 mmol) at 0C under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 14 h. The resulting mixture was poured onto ice water, extracted with ethyl acetate (2 x 20 mL). The combined ethyl acetate layer was washed with water, brine solution (2 x 10 mL). The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (methanolldichloromethane = 7/93) togive the titled compound (0.025 g, 17.1%) as a solid. HPLC: 96.6%; LCMS: m/z 385.25 [M+H] 1H NMR (400 MHz, Chloroform-d) 8.83 - 8.81 (m, 1H), 7.74 - 7.61 (m, 2H), 7.42 (dd, J = 9.4, 1.8 Hz, 1H), 7.23 - 7.18 (m, 2H), 6.85 - 6.79 (m, 2H), 6.77 (s, 2H), 5.05 -4.98 (m, 1H), 4.43 (d, J= 5.3 Hz, 2H), 4.08-4.00 (m, 2H), 3.27 (dd, J= 17.3,10.7 Hz, 1H), 3.12 (dd, J= 17.4, 7.1 Hz, 1H).

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 222; 223; 224

64
[ 95-76-1 ]
[ 139022-25-6 ]
C₁₄H₉Cl₂N₃O [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6679 - 6703

65
[ 158001-04-8 ]
[ 139022-25-6 ]

Yield	Reaction Conditions	Operation in experiment
78%	With lithium hydroxide monohydrate; In tetrahydrofuran; water; at 25℃; for 2h;	To a solution of ethyl imidazo[l ,2-a]pyridine-6-carboxylate (6.0 g, 36 mmol) in tetrahydrofuran (30 mL) and water (30 mL) was added lithium hydroxide hydrate (2.7 g, 63 mmol). The reaction mixture was stirred at 25 C for 2 hours. On completion, the mixture was acidified with 36% hydrochloric acid. The solid was collected, washed with water and dried in vacuo to give compound B-266 (4.0 g, 78% yield) as a yellow solid.
	With water; lithium hydroxide; In tetrahydrofuran; at 0 - 23℃; for 18h;	To a stirred solution of compound C (3.7g, 19.5 mmol, 1 eq) in THF (45 mL) was added a solution of LiOH (2.5 g, 58.4 mmol, 3 eq) in water (5 mL) drop wise at 0 C and the resulting mixture was stirred for 18 h at 23 C. The reaction mixture was concentrated in vacuo and the residue was diluted with water. The aqueous part was washed with ethyl acetate (20 mL), acidified with saturated aq. citric acid solution to pH 5. The organic components were extracted from the aq. part with 10% MeOHZ CH2CI2 (100 mL) and the organic layer was concentrated in vacuo to obtain the compound D (3 g) as off white solid which was used in the next step without further purification. (0299) [0289] LCMS: m/z = 163.1 [M+H], RT = 0.40 minutes; (Program Rl, Column W).

Reference： [1]Patent: WO2015/66371,2015,A1 .Location in patent: Paragraph 00528-00529
[2]Patent: WO2018/64135,2018,A1 .Location in patent: Paragraph 0287-0289

66
[ 139022-25-6 ]
[ 132213-07-1 ]

Yield	Reaction Conditions	Operation in experiment
26%	With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 80℃; for 3.5h;	To a solution of compound B-266 (4.3 g, 27 mmol) in anhydrous tetrahydrofuran (25 mL) was added borane dimethyl sulfide complex (5.8 mL, 10 N in dimethyl sulfide, 58 mmol) dropwise at 0 C. The resulting solution was stirred at 0 C for 0.5 hour, then heated to 80 C and stirred at this temperature for 3 hours. On completion, the mixture was quenched with methanol (10 mL) at 0 C, concentrated in vacuo and purified by silica gel chromatography [dichloromethane: methanol = 10: 1] to give compound B-267 (1.0 g, 26% yield) as a white solid. LCMS: (ES+) m/z (M+H)+ = 149.1 , tR = 0.279.

Reference： [1]Patent: WO2015/66371,2015,A1 .Location in patent: Paragraph 00530-00531

67
[ 139022-25-6 ]
[ 116355-16-9 ]

Reference： [1]Patent: WO2015/66371,2015,A1

68
[ 139022-25-6 ]
imidazo[1,2-a]pyridine-6-carbaldehyde oxime [ No CAS ]

Reference： [1]Patent: WO2015/66371,2015,A1

69
[ 139022-25-6 ]
(+/-)-4-(2,4-dimethoxybenzyl)-3-(imidazo[1,2-a]pyridin-6-yl)-4H-1'-azaspiro[[1,2,4]oxadiazole-5,3'-bicyclo[2.2.2]octane] [ No CAS ]

Reference： [1]Patent: WO2015/66371,2015,A1

70
[ 139022-25-6 ]
(+/-)-3-(imidazo[1,2-a]pyridin-6-yl)-4H-1'-azaspiro[[1,2,4]oxadiazole-5,3'-bicyclo[2.2.2]octane] [ No CAS ]

Reference： [1]Patent: WO2015/66371,2015,A1

71
(±)-(5-(((3-bromopyridin-2-yl)oxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine [ No CAS ]
[ 139022-25-6 ]
(±)-N-((5-(((3-bromopyridin-2-yl)oxy)methyl)-4,5-dihydroisoxazol-3-yl)methyl)imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.07 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of (5-(((3-bromopyridin-2-yl)oxy)methyl)-4,5-dihydroisoxazol-3- yl)methanamine (±) (product of step-6, 0.07 g, 0.245 mmol) and imidazo[l,2-a]pyridine-6- carboxylic acid (0.06 g, 0.367 mmol) in DMF (2 mL), added EDCI (0.094 g, 0.49 mmol), HOBT (0.066 g, 0.49 mmol) and DIPEA (0.17 mL, 0.98 mmol) at 0 C. The reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with ethyl acetate (250 mL). The organic phase was washed with aqueous sodium bicarbonate solution (50 mL), brine (3 x 50 mL), dried over sodium sulphate and concentrated in vacuum to afford a residue. The residue was purified by column chromatography on silica gel (dichloromethane/methanol = 96/4) to afford the title compound (0.07 g, 66 %) as a sticky solid. LCMS: m/z 431.40 [M+2] +.

Reference： [1]Patent: WO2016/12958,2016,A1 .Location in patent: Page/Page column 28

72
(±)-(5-(((3-bromopyridin-2-yl)oxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine [ No CAS ]
[ 139022-25-6 ]
(±)-N-((5-(((3-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)oxy)methyl)-4,5-dihydroisoxazol-3-yl)methyl)imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Reference： [1]Patent: WO2016/12958,2016,A1

73
(±)-(5-(((6'-fluoro-[3,3'-bipyridin]-4-yl)oxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride [ No CAS ]
[ 139022-25-6 ]
(±)-N-((5-(((6'-fluoro-[3,3'-bipyridin]-4-yl)oxy)methyl)-4,5-dihydroisoxazol-3-yl)methyl)imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.005 g	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	5-(((6'-Fluoro-[3,3'-bipyridin]-4-yl)oxy)methyl)-4,5-dihydroisoxazol-3- yl)methanamine hydrochloride (±) (product of step-5, 0.060 g, 0.198 mmol) was reacted with imidazo[l,2-a]pyridine-6-carboxylic acid (0.048 g, 0.297 mmol) in presence of HATU (0.113g, 0.297 mmol) and N,N-diisopropylethylamine (0.100 mL, 0.495 mmol) in DMF (10 mL) as described in the synthesis of step-7 of example- 1 to get the title compound (0.005g, 6%) as a solid. LCMS: m/z 447.1 [M+H]+; HPLC: 87.92%; JHNMR (400 MHz, Methanol- d4) delta 9.24 (s, 1H), 8.37 - 8.23 (m, 2H), 8.23 - 8.02 (m, 4H), 7.96 - 7.81 (m, 2H), 7.11 - 7.00 (dd, / = 8.7, 2.7 Hz, 1H), 6.57 - 6.47 (d, / = 7.4 Hz, 1H), 5.14 (s, 1H), 4.43 - 4.25 (m, 2H), 4.20 - 4.04 (dd, / = 14.5, 6.1 Hz, 1H), 3.47 - 3.10 (m, 2H), 3.07 - 2.91 (m, 1H).

Reference： [1]Patent: WO2016/12958,2016,A1 .Location in patent: Page/Page column 32; 33

74
(±)-(5-(([2,3'-bipyridin]-3-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride [ No CAS ]
[ 139022-25-6 ]
(±)-N-((5-(([2,3'-bipyridin]-3-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methyl)imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	(5-(([2 '-Bipyridin]-3-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride (±) (product of step-2, 0.320 g, 0.997 mmol) was reacted with imidazo[l,2- a]pyridine-6-carboxylic acid (0.193 g,1.197 mmol) in presence of BOP reagent (0.485 g, 1.096 mmol) and DIPEA (0.525 mL, 2.991 mmol ) in DMF (10 mL) at room temperature for 16 h. The reaction mixture was diluted with water (10 mL) extracted with ethyl acetate (50 mL) and washed with water (4 x 50 mL). The organic phase was dried over sodium sulphate and concentrated under reduced pressure to get a residue. The residue was purified by combiflash column chromatography (dichloromethane/methanol/triethylamine = 91/8/1) to afford the title compound (0.150 g, 35%) as a solid. LCMS: nt/z 428.7 [M+H] +; HPLC: 97.93 % ; NMR (400 MHz, DMSO-de): delta 9.16 - 9.12 (d, / = 1.8 Hz, 1H), 9.11 (s, 1H), 9.05 - 8.99 (t, / = 5.5, 5.5 Hz, 1H), 8.61 - 8.54 (dt, / = 3.3, 1.5, 1.5 Hz, 1H), 8.37 - 8.31 (d, / = 4.5 Hz, 1H), 8.30 - 8.25 (m, 1H), 8.11 (s, 1H), 7.68 - 7.60 (m, 4H), 7.51 - 7.45 (dd, / = 7.9, 4.8 Hz, 1H), 7.45 - 7.39 (dd, / = 8.4, 4.6 Hz, 1H), 5.01 - 4.91 (dq, / = 10.4, 5.6, 5.6, 5.4 Hz, 1H), 4.28 - 4.12 (m, 4H), 3.27 - 3.15 (dd, / = 17.6, 11.2 Hz, 1H), 3.00 - 2.86 (dd, / = 17.7, 7.1 Hz, 1H).

Reference： [1]Patent: WO2016/12958,2016,A1 .Location in patent: Page/Page column 38

75
(±)-(5-(([2,3'-bipyridin]-3-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methanamine hydrochloride [ No CAS ]
[ 139022-25-6 ]
(R)-N-((5-(([2,3'-bipyridin]-3-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methyl)imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]
(S)-N-((5-(([2,3'-bipyridin]-3-yloxy)methyl)-4,5-dihydroisoxazol-3-yl)methyl)imidazo[1,2-a]pyridine-6-carboxamide [ No CAS ]

Reference： [1]Patent: WO2016/12958,2016,A1

76
[ 1163729-53-0 ]
[ 139022-25-6 ]
[ 1453268-13-7 ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 8345 - 8368

77
[ 139022-25-6 ]
N-(4-((2-aminophenyl)carbamoyl)benzyl)imidazo[1,2-a]pyridine-7-carboxamide [ No CAS ]

Reference： [1]Patent: CN106916101,2017,A

78
[ 139022-25-6 ]
4-((imidazo[1,2-a]pyridine-7-carboxamido)methyl)benzoic acid [ No CAS ]

Reference： [1]Patent: CN106916101,2017,A

79
[ 18469-52-8 ]
[ 139022-25-6 ]
C₁₇H₁₅N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%		Imidazo [1,2-a] pyridine-6-carboxylic acid (200 mg, 1.00 mmol)EDC (230 mg, 1.20 mmol) and DMAP (146 mg, 1.20 mmol)Was dissolved in dry DMF (5 mL)Stirred at room temperature for 0.5 hour.A solution of methyl 4-aminomethylbenzoate (165 mg, 1.00 mmol)Stir for 2 hours.After completion of the reaction, the reaction solution was poured into ten times the amount of water,Solid precipitation.The solid was filtered,Filter cake after drying column chromatography to obtain intermediates 120mg,The yield was 37%

Reference： [1]Patent: CN106916101,2017,A .Location in patent: Paragraph 0158; 0159; 0160

80
2-fluoro-4-phenyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride [ No CAS ]
[ 139022-25-6 ]
(2-fluoro-4-phenyl-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)(imidazo[1,2-a]pyridin-6-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2017/218874,2017,A1 .Location in patent: Paragraph 00283

81
2-chloro-4-(3-fluorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride [ No CAS ]
[ 139022-25-6 ]
(2-chloro-4-(3-fluorophenyl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)(imidazo[1,2-a]pyridin-6-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2017/218874,2017,A1 .Location in patent: Paragraph 00290

82
2-fluoro-4-(2-fluorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine [ No CAS ]
[ 139022-25-6 ]
(2-fluoro-4-(2-fluorophenyl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)(imidazo[1,2-a]pyridin-6-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2017/218874,2017,A1 .Location in patent: Paragraph 00297

83
(S)-2-chloro-4-(4-fluorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine [ No CAS ]
[ 139022-25-6 ]
(S)-(2-chloro-4-(4-fluorophenyl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)(imidazo[1,2-a]pyridin-6-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2017/218874,2017,A1 .Location in patent: Paragraph 00304

84
(R)-2-chloro-4-(4-fluorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine [ No CAS ]
[ 139022-25-6 ]
(R)-(2-chloro-4-(4-fluorophenyl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)(imidazo[1,2-a]pyridin-6-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2017/218874,2017,A1 .Location in patent: Paragraph 00305

85
[ 139022-25-6 ]
[ 1117-97-1 ]
[ 1313726-20-3 ]

Yield	Reaction Conditions	Operation in experiment
600 mg	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In ethyl acetate; N,N-dimethyl-formamide; at 23 - 120℃; for 18h;	To a stirred solution of compound D (2.5 g,15.4 mmol, 1 eq) in DMF (50 mL) were added compound E (2.3g, 23.1 mmol, 1.5 eq), triethylamine (15.6 g, 154.3 mmol, 10 eq) and T3P (-50% in ethyl acetate, 14.8 g, 23.1 mmol, 1.5 eq) at 23 C and the resulting mixture was heated at 120 C for 18 h. The reaction mixture was cooled to RT, quenched with water and the organic components were extracted with 10% methanol/ CH2CI2. The organic layer was concentrated in vacuo and the crude material was purified by flash chromatography (Combiflash) using 100-200 mesh silica gel eluting with 10% MeOH/ CH2CI2 to obtain the compound F (600 mg, 20%) as off white solid. (0302) [0292] lH NMR (400 MHz, OMSO-d6) delta 9.03 (s, 1 H), 8.06 (s, 1 H), 7.64 (m, 1 H), 7.59 (d, / = 8 Hz, 1 H), 7.47-7.44 (m, 1 H), 3.61 (s, 3 H), 3.32 (s, 3 H); (0303) [0293] LCMS : m/z = 206.2 [M+H], RT = 0.54 minutes; (Program Rl , Column W).

Reference： [1]Patent: WO2018/64135,2018,A1 .Location in patent: Paragraph 0290-0293

86
[ 39658-41-8 ]
[ 139022-25-6 ]

Reference： [1]Patent: WO2018/64135,2018,A1

87
[ 139022-25-6 ]
cyclopropyl(imidazo[1,2-a]pyridin-6-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2018/64135,2018,A1

88
[ 139022-25-6 ]
C-cyclopropyl-C-(imidazo[1,2-a]pyridin-6-yl)methylamine [ No CAS ]

Reference： [1]Patent: WO2018/64135,2018,A1

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[ 139022-25-6 ]

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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

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. 139022-25-6 ] {[proInfo.proName]}

Quality Control of [ 139022-25-6 ]

Related Doc. of [ 139022-25-6 ]

Product Details of [ 139022-25-6 ]

Calculated chemistry of [ 139022-25-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 139022-25-6 ]

Application In Synthesis of [ 139022-25-6 ]

[ 139022-25-6 ] Synthesis Path-Upstream 1~9

[ 139022-25-6 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 139022-25-6 ]

Carboxylic Acids

Related Parent Nucleus of [ 139022-25-6 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 139022-25-6 ]

Related Parent Nucleus of
[ 139022-25-6 ]