[ CAS No. 1220220-21-2 ] {[proInfo.proName]}

Name: 1220220-21-2|N-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide|98%
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SKU: A189941
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Quality Control of [ 1220220-21-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1220220-21-2 ]

SDS Specification

Alternatived Products of [ 1220220-21-2 ]

Product Details of [ 1220220-21-2 ]

CAS No. :	1220220-21-2	MDL No. :	MFCD11878181
Formula :	C₁₃H₁₉BN₂O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LXSZMGQQXZXQKX-UHFFFAOYSA-N
M.W :	262.11	Pubchem ID :	49760417
Synonyms :

Calculated chemistry of [ 1220220-21-2 ]

Physicochemical Properties

Num. heavy atoms :	19
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.54
Num. rotatable bonds :	3
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	75.03
TPSA :	60.45 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.94 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.35
Log Po/w (WLOGP) :	1.15
Log Po/w (MLOGP) :	0.45
Log Po/w (SILICOS-IT) :	0.91
Consensus Log Po/w :	0.77

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.35
Solubility :	1.17 mg/ml ; 0.00445 mol/l
Class :	Soluble
Log S (Ali) :	-2.22
Solubility :	1.57 mg/ml ; 0.006 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.01
Solubility :	0.0254 mg/ml ; 0.0000968 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.83

Safety of [ 1220220-21-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1220220-21-2 ]

* 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 [ 1220220-21-2 ]
Downstream synthetic route of [ 1220220-21-2 ]

[ 1220220-21-2 ] Synthesis Path-Upstream 1~2

1
[ 1026796-81-5 ]
[ 73183-34-3 ]
[ 1220220-21-2 ]

Yield	Reaction Conditions	Operation in experiment
91.1%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 100℃; Inert atmosphere; Industrial scale	A 1 L four-necked flask equipped with a magnetic stirrer, a thermometer, a reflux condenser and a bubbler was charged55.91 g (0.26 mol) of 2-acetylamino-4-bromopyridine, 66.02 g (0.26 mol) of bis (pinacolato) diboron and 76.44 g(0.78mol), 450mL of dioxane was added and stirred. Under nitrogen atmosphere, 3.81g (0.0051mol) of ferrocenepalladium chloride was added,Temperature to 100 reaction 18 to 24 hours,TLC control to the end of the reaction, the temperature was precipitated solids, beating filtration, methanol was added 500mL dissolved, filtered and evaporated to dryness, add heptane beating, to give the product 62.08g, yield 91.1percent.
29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 80℃; for 3.5 h; Inert atmosphere	Step 2: N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol, 1.0 equiv.), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)Cl₂ (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80° C. for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 min and then filtered. The organic solution was concentrated and the residue was re-crystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29percent) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J=6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).
29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 80℃; for 3.5 h; Inert atmosphere	1001161 To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol), 4,4,4,4,5,5,5,5- octamethyl-2,2-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)C12 (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80 °C for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 mm and then filtered. The organic solution was concentrated and the residue was recrystallized from EtOAc to give N[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29percent) as a white solid. ‘H NMR (400 MHz, DMSO-d6): 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J= 6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).

29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 80℃; for 3.5 h; Inert atmosphere	[00180] To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol), 4,4,4,4,5,5,5,5’- octamethyl-2,2’-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)C12 (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80°C for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 mm and then filtered. The organic solution was concentrated and the residue was recrystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29percent) as a white solid. 1H NEVER (400 JVEFIz, DMSO-ds): 6 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J= 6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).
29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 80℃; for 3.5 h; Inert atmosphere	Step 2: N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)Cl₂ (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80° C. for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 min and then filtered. The organic solution was concentrated and the residue was recrystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29percent) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J=6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).
29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 80℃; for 3.5 h; Inert atmosphere	Step 2: N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)Cl₂ (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80° C. for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 min and then filtered. The organic solution was concentrated and the residue was recrystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29percent) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J=6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).

Reference： [1] Patent: CN103601745, 2017, B, . Location in patent: Paragraph 0025; 0026
[2] Angewandte Chemie - International Edition, 2016, vol. 55, # 36, p. 10890 - 10894[3] Angew. Chem., 2016, vol. 128, p. 11050 - 11054,5
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 13, p. 5613 - 5637
[5] Patent: US2013/165464, 2013, A1, . Location in patent: Paragraph 0835
[6] Patent: WO2015/108881, 2015, A1, . Location in patent: Paragraph 00116
[7] Patent: WO2015/108861, 2015, A1, . Location in patent: Paragraph 00180
[8] Patent: US2015/225422, 2015, A1, . Location in patent: Paragraph 0235; 0237
[9] Patent: US2016/333007, 2016, A1, . Location in patent: Paragraph 0227

2
[ 84249-14-9 ]
[ 1220220-21-2 ]

Reference： [1] Patent: US2013/165464, 2013, A1,
[2] Patent: WO2015/108881, 2015, A1,
[3] Patent: WO2015/108861, 2015, A1,
[4] Patent: US2015/225422, 2015, A1,
[5] Patent: US2016/333007, 2016, A1,
[6] Journal of Medicinal Chemistry, 2017, vol. 60, # 13, p. 5613 - 5637
[7] Patent: CN103601745, 2017, B,

[ 1220220-21-2 ] Synthesis Path-Downstream 1~88

1
[ 1220220-21-2 ]
[ 1429893-42-4 ]
[ 1429892-36-3 ]

Yield	Reaction Conditions	Operation in experiment
17%	With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 150℃; for 0.5h;Inert atmosphere; Sealed tube; Microwave irradiation;	Production of compounds of the formula [I-i] by route (V4)N-{4- [2-(4-Fluorophenyl)pyrazolo [1,5-a] pyrimidin-3-yl] pyridin-2-yl} acetamide [I-i-1 ]3-Bromo-2-(4-fluorophenyl)pyrazolo[l,5-a]pyrimidine (150 mg, 0.51 mmol) and N-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (148 mg, 0.56 mmol, 1.1 eq) are dissolved in 1.5mL 1,4-dioxan. To this mixture, bis(tricyclohexylphosphine)palladium(II)-dichloride (57 mg, 0.07 mmol, 0.15eq) and 0.83 mL sodium carbonate solution (2 molar) are added. The reaction mixture is flushed with argon for 5 mins and then sealed. Next the mixture is heated for 30min at 150C in the microwave (Biotage). The reaction mixture is then poured in water and extracted with dichloromethane (3 x 20 mL). The organic layer is dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The crude material is purified by column chromatography using silica gel in heptane and ethyl acetate (1 :0 to 1 :1) as eluent and 0.03 g (17%) of N- {4-[2-(4-fluorophenyl)pyrazolo[l,5-a]pyrimidin-3- yl]pyridin-2-yl} acetamide are obtained as a white solid.¾-NMR (300MHz, DMSO): delta = 10.48 (bs, 1H), 9.23 (dd, 1H), 8.69 (dd, 1H), 8.30 (s, 1H), 8.25 (d, 1H), 7.62 (m, 2H), 7.31 (m, 2H), 7.22 (dd, 1H), 7.11 (dd, 1H), 2.05 (s, 3H) ppmlogP (pH 2.7): 1.47MS (ESI): 348.1 ([M+H]+)

Reference： [1]Patent: WO2013/50437,2013,A1 .Location in patent: Page/Page column 105-106

2
[ 84249-14-9 ]
[ 1220220-21-2 ]

Reference： [1]Patent: US2013/165464,2013,A1
[2]Patent: WO2015/108881,2015,A1
[3]Patent: WO2015/108861,2015,A1
[4]Patent: US2015/225422,2015,A1
[5]Patent: US2016/333007,2016,A1
[6]Journal of Medicinal Chemistry,2017,vol. 60,p. 5613 - 5637
[7]Patent: CN103601745,2017,B

3
[ 1026796-81-5 ]
[ 73183-34-3 ]
[ 1220220-21-2 ]

Yield	Reaction Conditions	Operation in experiment
91.1%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃;Inert atmosphere; Industrial scale;	A 1 L four-necked flask equipped with a magnetic stirrer, a thermometer, a reflux condenser and a bubbler was charged55.91 g (0.26 mol) of 2-acetylamino-4-bromopyridine, 66.02 g (0.26 mol) of bis (pinacolato) diboron and 76.44 g(0.78mol), 450mL of dioxane was added and stirred. Under nitrogen atmosphere, 3.81g (0.0051mol) of ferrocenepalladium chloride was added,Temperature to 100 reaction 18 to 24 hours,TLC control to the end of the reaction, the temperature was precipitated solids, beating filtration, methanol was added 500mL dissolved, filtered and evaporated to dryness, add heptane beating, to give the product 62.08g, yield 91.1%.
29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 3.5h;Inert atmosphere;	Step 2: N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol, 1.0 equiv.), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)Cl2 (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80 C. for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 min and then filtered. The organic solution was concentrated and the residue was re-crystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29%) as a white solid. 1H NMR (400 MHz, DMSO-d6): delta 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J=6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).
29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 3.5h;Inert atmosphere;	1001161 To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol), 4,4,4,4,5,5,5,5- octamethyl-2,2-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)C12 (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80 C for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 mm and then filtered. The organic solution was concentrated and the residue was recrystallized from EtOAc to give N[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29%) as a white solid. ?H NMR (400 MHz, DMSO-d6): 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J= 6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).

29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 3.5h;Inert atmosphere;	[00180] To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol), 4,4,4,4,5,5,5,5?- octamethyl-2,2?-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)C12 (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80C for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 mm and then filtered. The organic solution was concentrated and the residue was recrystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29%) as a white solid. 1H NEVER (400 JVEFIz, DMSO-ds): 6 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J= 6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).
29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 3.5h;Inert atmosphere;	Step 2: N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)Cl2 (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80 C. for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 min and then filtered. The organic solution was concentrated and the residue was recrystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29%) as a white solid. 1H NMR (400 MHz, DMSO-d6): delta 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J=6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).
29%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 3.5h;Inert atmosphere;	Step 2: N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide To a mixture of N-(4-bromopyridin-2-yl)acetamide (17.2 g, 80 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (26.4 g, 104 mmol), Pd(dppf)Cl2 (11.7 g, 16 mmol) and KOAc (23.6 g, 240 mmol) under an atmosphere of nitrogen was added anhydrous DMF (1500 mL). The mixture was allowed to stir at 80 C. for 3.5 h. The solvent was removed and the residue was diluted with EtOAc (1000 mL). Activated carbon (100 g) was added. The slurry was heated at reflux for 5 min and then filtered. The organic solution was concentrated and the residue was recrystallized from EtOAc to give N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (6.1 g, 29%) as a white solid. 1H NMR (400 MHz, DMSO-d6): delta 1.29 (s, 12H), 2.09 (s, 3H), 7.24 (dd, J=6.0, 1.2 Hz, 1H), 8.30-8.33 (m, 2H), 10.47 (br s, 1H).

Reference： [1]Patent: CN103601745,2017,B .Location in patent: Paragraph 0025; 0026
[2]Angewandte Chemie - International Edition,2016,vol. 55,p. 10890 - 10894
Angew. Chem.,2016,vol. 128,p. 11050 - 11054,5
[3]Journal of Medicinal Chemistry,2017,vol. 60,p. 5613 - 5637
[4]Patent: US2013/165464,2013,A1 .Location in patent: Paragraph 0835
[5]Patent: WO2015/108881,2015,A1 .Location in patent: Paragraph 00116
[6]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00180
[7]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0235; 0237
[8]Patent: US2016/333007,2016,A1 .Location in patent: Paragraph 0227

4
[ 1220220-21-2 ]
[ 1610520-76-7 ]
[ 1610520-77-8 ]

Yield	Reaction Conditions	Operation in experiment
4.4%	With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; potassium carbonate; In water; isopropyl alcohol; at 130℃; for 0.5h;Microwave irradiation;	To a suspension of 7-bromo-5-methyl-2-((1-(methylsulphonyl)piperidin-4-ylidene)methyl)thieno[3,2- c]pyridin-4(5H)-one (for a preparation see Intermediate 61 , 200 mg, 0.479 mmol) followed by Lambda/-(4- (4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (251 mg, 0.958 mmol) and potassium carbonate (265 mg, 1.917 mmol) in isopropanol (4 mL) and water (3 mL) was added PEPPSI (32.6 mg, 0.048 mmol) catalyst. The reaction mixture was heated to 130 C for 30 minutes in the microwave. The reaction was hydrolyzed using a saturated aqueous solution of ammonium chloride (30 mL). The layers were separated and the aqueous phase was extracted with DCM (3 x 30 mL). The combined organic fractions were dried over magnesium sulphate, filtered and concentrated in vacuo to give a dark brown oil. The crude material was purified by chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane. The desired product co-eluted with various impurities. The appropriate fractions were concentrated, redissolved in 1 :1 DMSO/MeOH, and filtered through a bond elute cartridge to remove insoluble impurities. The material was then repurified by MDAP in three portions to give Lambda/- (4-(5-methyl-2-((1-(methylsulphonyl)piperidin-4-ylidene)methyl)-4-oxo-4,5-dihydrothieno[3,2- c]pyridin-7-yl)pyridin-2-yl)acetamide (10 mg, 4.4% yield) as a white solid. LCMS (2 min, Formic Acid): Rt = 0.74 min, MH+ = 473

Reference： [1]Patent: WO2014/78257,2014,A1 .Location in patent: Page/Page column 100

5
[ 1220220-21-2 ]
[ 1610520-41-6 ]
[ 1610519-37-3 ]

Yield	Reaction Conditions	Operation in experiment
39.9%	With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; potassium carbonate; In water; isopropyl alcohol; at 80℃;Inert atmosphere;	To a stirred solution of (R)-7-bromo-5-methyl-2-((2-methyl-4-(methylsulphonyl)piperazin-1 - yl)methyl)thieno[3,2-c]pyridin-4(5H)-one (for a preparation see Intermediate 21 , 100 mg, 0.230 mmol) in Isopropanol (2 mL) and water (2 mL) was added A/-(4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)pyridin-2-yl)acetamide (121 mg, 0.460 mmol) [PCT Int. Appl WO2012021615(A1 )] followed by potassium carbonate (127 mg, 0.921 mmol), and PEPPSI (15.64 mg, 0.023 mmol) catalyst. The reaction was heated to 80 C and stirred under an atmosphere of nitrogen for 16 hrs. Further A/-(4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (61 mg, 0.1 15 mmol) was added and the mixture heated at 80 C overnight. The mixture was diluted with chloroform (30 mL) and saturated ammonium chloride solution (30 mL) before being passed through a 2.5 g Celite cartridge. The filtrate phases were separated and the aqueous phase was back extracted with chloroform (30 mL). The organic phases were combined, dried over magnesium sulphate, and concentrated under reduced pressure. The crude material was triturated with diethyl ether to give a solid which was suspended in MeOH (2 mL) and refluxed at 70 C for 30 minutes. The suspension was allowed to cool to room temperature and left to stand overnight. The solid was filtered through a small glass filter funnel and washed with methanol. The product was again suspended in MeOH (1 mL) and refluxed for 30 minutes. The suspension was allowed to cool to room temperature and left to stand overnight. The product was filtered and washed with methanol (3 x 10 mL) to give (R)-/V-(4-(5-methyl-2-((2-methyl-4-(methylsulphonyl)piperazin-1 -yl)methyl)-4-oxo- 4,5-dihydrothieno[3,2-c]pyridin-7-yl)pyridin-2-yl)acetamide (45 mg, 0.092 mmol, 39.9% yield) as a pale yellow solid. LCMS (2 min, Formic Acid): Rt = 0.51 min, MH+ = 490

Reference： [1]Patent: WO2014/78257,2014,A1 .Location in patent: Page/Page column 203; 204

6
[ 1220220-21-2 ]
[ 1610520-62-1 ]
[ 1610521-06-6 ]

Yield	Reaction Conditions	Operation in experiment
	With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; potassium carbonate; In water; isopropyl alcohol; at 60 - 100℃;Inert atmosphere;	A suspension of 7-bromo-2-(hydroxymethyl)-5-methylthieno[3,2-c]pyridin-4(5H)-one (Intermediate 43) (1 g, 3.65 mmol) in isopropanol (25 ml.) and water (25 ml.) was treated with Lambda/-(4-(4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (1 .912 g, 7.30 mmol) followed by potassium carbonate (2.017 g, 14.59 mmol), and lastly the PEPPSI catalyst (0.248 g, 0.365 mmol). The reaction was warmed to 60 C and stirred under nitrogen overnight. The reaction mixture was treated with a fresh portion of the PEPPSI (0.248 g, 0.365 mmol) catalyst and heated to 100 C for 4.5 hours. The reaction was cooled to room temperature, diluted with EtOAc (50 ml_), and filtered through a 10g Celite frit to remove inorganic impurities. The filtrated was concentrated under reduced pressure to give a yellow solid. The material was triturated with diethyl ether to give a yellow solid which was suspended in MeOH and heated to 100 C. The mixture was refluxed for 20 minutes and allowed to cool to room temperature overnight. The solids were collected in a glass filter funnel and washed with cold MeOH (approx. 25 mL). The product was dried under vacuum for 20 minutes and transferred to a vacuum oven to dry for several hours to give the title compound (1.38 g, 4.19 mmol, 1 15 % yield), as a cream coloured solid. 1H NMR (400MHz, DMSO-d6) delta-ppm 10.6 (1 H, s), 8.58 (1 H, s), 8.50 (1 H, s), 8.40 (1 H, d), 7.94 (1 H, s), 7.40 (1 H, s), 7.33 (1 H, d), 4.71 (2H, s), 3.60 (3H, s), 2.12 (3H, s).

Reference： [1]Patent: WO2014/78257,2014,A1 .Location in patent: Page/Page column 114; 115

7
[ 1220220-21-2 ]
7-bromo-2-((3,3-difluoropiperidin-1-yl)methyl)-5-methylfuro[3,2-c]pyridin-4(5H)-one [ No CAS ]
N-(4-(2-((3,3-difluoropiperidin-1-yl)methyl)-5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridin-7-yl)pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In ethanol; toluene; at 120℃; for 0.333333h;Microwave irradiation;	Example 18: N-(4-(2-((3,3-difluoropiperidin-1-yl)methyl)-5-methyl-4-oxo-4,5-dihvdrofuror3,2- c1pyridin-7-yl)pyridin-2-yl)acetamide Bromo-2-((3,3-difluoropiperidin-1-yl)methyl)-5-methylfuro[3,2-c]pyridin-4( (for a preparation see Intermediate 13, 75 mg, 0.208 mmol), A/-(4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin- 2-yl)acetamide (Milestone Pharm tech USA) (82 mg, 0.31 1 mmol), potassium carbonate (143 mg, 1.038 mmol) and 5/s(triphenylphosphine)palladium(ll) chloride (7.29 mg, 10.38 muiotaetaomicronIota) were dissolved in EtOH (2 mL) and toluene (2 mL) and heated in a microwave for 20 min at 120C. Ethyl acetate (15 mL) was added and the mixture was dried over MgS04, filtered and evaporated. The residue was purified by chromatography on silica gel using a 0-5 % MeOH/DCM gradient. The appropriate fractions were combined and evaporated in vacuo to give A/-(4-(2-((3,3-difluoropiperidin-1-yl)methyl)- 5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridin-7-yl)pyridin-2-yl)acetamide (55 mg, 64 %) as a translucent oil. LCMS (2 min, High pH): Rt = 0.78 min, MH+ 417

Reference： [1]Patent: WO2014/140077,2014,A1 .Location in patent: Page/Page column 68-69

8
[ 1220220-21-2 ]
7-bromo-2-((3-fluoropiperidin-1-yl)methyl)-5-methylfuro[3,2-c]pyridin-4(5H)-one [ No CAS ]
N-(4-(2-((3-fluoropiperidin-1-yl)methyl)-5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridin-7-yl)pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In ethanol; toluene; at 120℃; for 0.333333h;Microwave irradiation;	see Intermediate 15, 82.5 mg, 0.240 mmol), A/-(4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)pyridin-2-yl)acetamide (Milestone Pharm tech USA) (95 mg, 0.361 mmol), potassium carbonate (166 mg, 1.202 mmol) and 5/s(triphenylphosphine)palladium(ll) chloride (8.44 mg, 0.012 mmol) were dissolved in EtOH (2 mL) and toluene (2 mL) and heated in a microwave for 20 min at 120C. Ethyl acetate (15 mL) was added and the mixture was dried over MgS04, filtered and evaporated. The residue was purified by chromatography on silica gel using a 0-10 % MeOH/DCM gradient. The appropriate fractions were combined and evaporated in vacuo to give A/-(4-(2-((3,3-difluoropiperidin- 1-yl)methyl)-5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridin-7-yl)pyridin-2-yl)acetamide (55 mg, 64 %) as a bright yellow solid LCMS (2 min, High pH): Rt = 0.73 min, MH+ 399

Reference： [1]Patent: WO2014/140077,2014,A1 .Location in patent: Page/Page column 68

9
[ 1220220-21-2 ]
7-bromo-5-methyl-2-((4-(methylsulfonyl)piperazin-1-yl)methyl)furo[3,2-c]pyridin-4(5H)-one [ No CAS ]
N-(4-(5-methyl-2-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4,5-dihydrofuro[3,2-c]pyridin-7-yl)pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39.6%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; at 120℃; for 2h;Microwave irradiation; Sealed tube;	To a stirred suspension of 7-bromo-5-methyl-2-((4-(methylsulfonyl)piperazin-1-yl)methyl)furo[3,2- c]pyridin-4(5H)-one (for a preparation see Intermediate 3, 100 mg, 0.247 mmol), Lambda/-(4-(4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (Milestone Pharma Tech) (104 mg, 0.396 mmol), potassium carbonate (103 mg, 0.742 mmol) in 1 ,2-DME (3 imL) in a microwave vial, was added fefra/ /s(triphenylphosphine)palladium(0) (14.29 mg, 0.012 mmol). The microwave vial was sealed and heated in a microwave at 120C for 2 h. The mixture was dissolved in methanol and concentrated in vacuo. The residue was re-dissolved in methanol and loaded onto an SCX cartridge (1 g) and eluted with 2M ammonia in methanol. Appropriate fractions were combined and concentrated in vacuo. The residue was purified by MDAP. Appropriate fractions were combined

Reference： [1]Patent: WO2014/140077,2014,A1 .Location in patent: Page/Page column 77

10
[ 1220220-21-2 ]
(R)-7-bromo-5-methyl-2-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)furo[3,2-c]pyridin-4(5H)-one [ No CAS ]
(R)-N-{4-(5-methyl-2-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4,5-dihydrofuro[3,2-c]pyridin-7-yl)pyridin-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With trans-bis(triphenylphosphine)palladium dichloride; potassium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 0.333333h;Microwave irradiation;	tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (Milestone Pharma tech USA) (432 mg, 1.650 mmol), potassium carbonate (456 mg, 3.30 mmol) and 5/s(triphenylphosphine)palladium(ll) chloride (57.9 mg, 0.082 mmol) in water (1.5 mL) and 1 ,2-DME (4.5 mL) was heated in a microwave at 120 C for 20 minutes. The cooled reaction mixture was diluted with ethyl acetate and the solution

Reference： [1]Patent: WO2014/140077,2014,A1 .Location in patent: Page/Page column 62

11
[ 1220220-21-2 ]
2-[4-bromo-1-(cyclopropylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]methyl}-1H-isoindole-1,3(2H)-dione [ No CAS ]
N-{4-[7-(aminomethyl)-1-(cyclopropylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-yl}acetamide formic acid [ No CAS ]

Reference： [1]Patent: WO2015/108881,2015,A1

12
[ 1220220-21-2 ]
2-[4-bromo-1-(cyclopropylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]methyl}-1H-isoindole-1,3(2H)-dione [ No CAS ]
N-(4-{1-(cyclopropylsulfonyl)-7-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1H-pyrrolo[2,3-c]pyridin-4-yl}pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 130℃; for 1.5h;Inert atmosphere; Microwave irradiation;	j00138j A microwave vial was charged with N- [4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2- yl)pyridin-2-yl]acetamide (202 mg, 0.77 mmol), [1,1 -bis(diphenylphosphino)ferrocene] dichloropalladium(II), complex with dichloromethane (1:1) (32 mg, 0.04 mmol) and purged with nitrogen. 4-bromo- 1 -(cyclopropylsulfonyl)- 1 H-pyrazolo [3 ,4-c]pyridine (188 mg, 0.62 mmol) in 1,4- dioxane (5.0 mL) was added followed by 2.00 M of potassium carbonate in water (0.62 mL, 1.24 mmol). The reaction mixture was heated in an oil bath at 90 C for 15 mm. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residue was purified by column chromatography. The resulting off white solid was triturated with MeOH, filtered, and dried under vacuum to yield N-{4-[1-(cyclopropylsulfonyl)-1H- pyrazolo[3,4-c]pyridin-4-yl]pyridin-2-yl}acetamide (191 mg, 86%) as a white solid; Followed the procedure described in Step 2 of Example 5 with the following modification:Heated at 130 C for 30 mm. under microwave irradiation to yield N-(4- { 1 -(cyclopropylsulfonyl)-7-[(1 ,3- dioxo- 1 ,3-dihydro-2H-isoindol-2-yl)methyl]- 1H-pyrrolo[2,3-c]pyridin-4-yl}pyridin-2-yl)acetamide (70 mg, 57%) LCMS (FA): m/z = 516.4 (M+H).

Reference： [1]Patent: WO2015/108881,2015,A1 .Location in patent: Paragraph 00138; 00153

13
[ 1220220-21-2 ]
4-bromo-7-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine [ No CAS ]
N-{4-[7-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53.0%	With potassium carbonate; In 1,4-dioxane; water; at 180℃; for 1h;Inert atmosphere; Microwave irradiation;	j00132j A microwave vial was charged with N- [4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2- yl)pyridin-2-yl]acetamide (140 mg, 0.550 mmol) and SiliaCat DPP-Pd (68 mg, 0.0 17 mmol). The reaction mixture was purged with nitrogen and a solution of 4-bromo-7-methyl- 1 -(phenylsulfonyl)- 1H- pyrrolo[2,3-c]pyridine (102 mg, 0.290 mmol) inl,4-dioxane (2 mL) was added follow by 1.00 M potassium carbonate in water (0.293 mL, 0.293 mmol). The reaction mixture was heated at 180 C in the microwavae for 60 mm. The mixture was filtered through a bed of celite and which was further washed with ethyl acetate. The filtrate was concentrated by rotary evaporation and purified by prep HPLC to yield N- {4-[7-methyl- 1 -(phenylsulfonyl)- 1H-pyffolo[2,3-c]pyridin-4-yl]pyridin-2-yl} acetamide (63 mg, 53.0%). LCMS (FA): m/z = 407.1 (M+H).
53.0%	With potassium carbonate; In 1,4-dioxane; water; at 180℃; for 1h;Microwave irradiation; Inert atmosphere;	Step 3: N-{4-[7-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-yl}acetamide A microwave vial was charged with <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (140 mg, 0.550 mmol) and SiliaCat DPP-Pd (68 mg, 0.017 mmol). The reaction mixture was purged with nitrogen and a solution of 4-bromo-7-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine (102 mg, 0.290 mmol) in 1,4-dioxane (2 mL) was added follow by 1.00 M potassium carbonate in water (0.293 mL, 0.293 mmol). The reaction mixture was heated at 180 C. in the microwave for 60 min. The mixture was filtered through a bed of celite and which was further washed with ethyl acetate. The filtrate was concentrated by rotary evaporation and purified by prep HPLC to yield N-{4-[7-methyl-1-phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-yl}acetamide (63 mg, 53.0%). LCMS (FA): m/z=407.1 (M+H).

Reference： [1]Patent: WO2015/108881,2015,A1 .Location in patent: Page/Page column 00132
[2]Patent: US2016/333007,2016,A1 .Location in patent: Paragraph 0250

14
[ 1220220-21-2 ]
C₈H₇BrN₂O₂S [ No CAS ]
N-{4-[1-(methylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); In 1,2-dimethoxyethane; at 180℃; for 1h;Inert atmosphere; Microwave irradiation;	j00132j A microwave vial was charged with N- [4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2- yl)pyridin-2-yl]acetamide (140 mg, 0.550 mmol) and SiliaCat DPP-Pd (68 mg, 0.0 17 mmol). The reaction mixture was purged with nitrogen and a solution of 4-bromo-7-methyl- 1 -(phenylsulfonyl)- 1H- pyrrolo[2,3-c]pyridine (102 mg, 0.290 mmol) inl,4-dioxane (2 mL) was added follow by 1.00 M potassium carbonate in water (0.293 mL, 0.293 mmol). The reaction mixture was heated at 180 C in the microwavae for 60 mm. The mixture was filtered through a bed of celite and which was further washed with ethyl acetate. The filtrate was concentrated by rotary evaporation and purified by prep HPLC to yield N- {4-[7-methyl- 1 -(phenylsulfonyl)- 1H-pyffolo[2,3-c]pyridin-4-yl]pyridin-2-yl} acetamide (63 mg, 53.0%).

Reference： [1]Patent: WO2015/108881,2015,A1 .Location in patent: Paragraph 00132; 00133

15
[ 1220220-21-2 ]
4-bromo-1-(cyclopropylsulfonyl)-1H-pyrrolo[2,3-c]pyridine [ No CAS ]
N-{4-[1-(cyclopropylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 180℃; for 1h;Inert atmosphere; Microwave irradiation;	j00132j A microwave vial was charged with N- [4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2- yl)pyridin-2-yl]acetamide (140 mg, 0.550 mmol) and SiliaCat DPP-Pd (68 mg, 0.0 17 mmol). The reaction mixture was purged with nitrogen and a solution of 4-bromo-7-methyl- 1 -(phenylsulfonyl)- 1H- pyrrolo[2,3-c]pyridine (102 mg, 0.290 mmol) inl,4-dioxane (2 mL) was added follow by 1.00 M potassium carbonate in water (0.293 mL, 0.293 mmol). The reaction mixture was heated at 180 C in the microwavae for 60 mm. The mixture was filtered through a bed of celite and which was further washed with ethyl acetate. The filtrate was concentrated by rotary evaporation and purified by prep HPLC to yield N- {4-[7-methyl- 1 -(phenylsulfonyl)- 1H-pyffolo[2,3-c]pyridin-4-yl]pyridin-2-yl} acetamide (63 mg, 53.0%).

Reference： [1]Patent: WO2015/108881,2015,A1 .Location in patent: Paragraph 00132; 00133

16
[ 1220220-21-2 ]
4-bromo-1-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridine [ No CAS ]
N-{4-[1-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-4-yl]pyridin-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 0.25h;Inert atmosphere;	j00138j A microwave vial was charged with N- [4-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2- yl)pyridin-2-yl]acetamide (202 mg, 0.77 mmol), [1,1 -bis(diphenylphosphino)ferrocene] dichloropalladium(II), complex with dichloromethane (1:1) (32 mg, 0.04 mmol) and purged with nitrogen. 4-bromo- 1 -(cyclopropylsulfonyl)- 1 H-pyrazolo [3 ,4-c]pyridine (188 mg, 0.62 mmol) in 1,4- dioxane (5.0 mL) was added followed by 2.00 M of potassium carbonate in water (0.62 mL, 1.24 mmol). The reaction mixture was heated in an oil bath at 90 C for 15 mm. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residue was purified by column chromatography. The resulting off white solid was triturated with MeOH, filtered, and dried under vacuum to yield N-{4-[1-(cyclopropylsulfonyl)-1H- pyrazolo[3,4-c]pyridin-4-yl]pyridin-2-yl}acetamide (191 mg, 86%) as a white solid. LCMS (AA): m/z = 358.4 (M+H).
86%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 0.25h;Inert atmosphere;	Step 2: N-{4-[1-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-4-yl]pyridin-2-yl}acetamide A microwave vial was charged with <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (202 mg, 0.77 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (32 mg, 0.04 mmol) and purged with nitrogen, 4-bromo-1-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridine (188 mg, 0.62 mmol) in 1,4-dioxane (5.0 mL) was added followed by 2.00 M of potassium carbonate in water (0.62 mL, 1.24 mmol). The reaction mixture was heated in an oil bath at 90 C. for 15 min. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residue was purified by column chromatography. The resulting off white solid was triturated with MeOH, filtered, and dried under vacuum to yield N-{4-[1-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-4-yl]pyridin-2-yl}acetamide (191 mg, 86%) as a white solid. LCMS (AA): m/z=358.4 (M+H).

Reference： [1]Patent: WO2015/108881,2015,A1 .Location in patent: Paragraph 00138
[2]Patent: US2016/333007,2016,A1 .Location in patent: Paragraph 0259

17
[ 1220220-21-2 ]
N-(5-[(2-chloro-4-fluorophenyl)sulfonyl]amino}-6-methyl-3,4'-bipyridin-2'-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2015/108861,2015,A1
[2]Patent: US2015/225422,2015,A1

18
[ 1220220-21-2 ]
4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-amine [ No CAS ]

Reference： [1]Patent: WO2015/108861,2015,A1
[2]Patent: US2015/225422,2015,A1

19
[ 1220220-21-2 ]
methyl [4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-yl]carbamate [ No CAS ]

Reference： [1]Patent: WO2015/108861,2015,A1
[2]Patent: US2015/225422,2015,A1

20
[ 1220220-21-2 ]
N-(5-(N-(tert-butyl)sulfamoyl)-4-methyl-[3,4’-bipyridin]-2'-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2015/108861,2015,A1
[2]Patent: US2015/225422,2015,A1

21
[ 1220220-21-2 ]
N-[5-(1,3-oxazol-2-ylamino)-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]

Reference： [1]Patent: WO2015/108861,2015,A1
[2]Patent: US2015/225422,2015,A1

22
[ 1220220-21-2 ]
N-[5-(1,3-benzoxazol-2-ylamino)-6-methyl-3,4’-bipyridin-2'-yl]acetamide [ No CAS ]

Reference： [1]Patent: WO2015/108861,2015,A1
[2]Patent: US2015/225422,2015,A1

23
[ 1083326-15-1 ]
[ 1220220-21-2 ]
N-[6-amino-5-(dimethylsulfamoyl)-3,4'-bipyridin-2'-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 18h;Inert atmosphere; Sealed tube;	[00211] <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.127 g, 0.483 mmol), 2-amino-5-bromo-N,N-dimethylpyridine-3-sulfonamide (0.176 g, 0.628 mmol), potassium carbonate (134 mg, 0.966 mmol), 1,4-dioxane:water (4.26 niL, 6:1 mixture) and Pd(dppf)C12 (19.9 mg, 0.024 mmol) were combined in a reaction vial, flushed with nitrogen and sealed. The reaction mixture was heated at 120 C in an oil bath for 18 h. The reaction mixture was cooled to ii, filtered through celite and washed with DCM. The crude material was purified by prep HPLC to yield N-[6-amino-5- (dimethylsulfamoyl)-3,4?-bipyridin-2?-yl]acetamide (0.047 g, 26%). LCMS (AA): m/z 336.0 (M+H).
26%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 18h;Inert atmosphere; Sealed tube;	Step 2: N-[6-amino-5-(dimethylsulfamoyl)-3,4'-bipyridin-2'-yl]acetamide <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.127 g, 0.483 mmol), 2-amino-5-bromo-N,N-dimethylpyridine-3-sulfonamide (0.176 g, 0.628 mmol), potassium carbonate (134 mg, 0.966 mmol), 1,4-dioxane:water (4.26 mL, 6:1 mixture) and Pd(dppf)Cl2 (19.9 mg, 0.024 mmol) were combined in a reaction vial, flushed with nitrogen and sealed. The reaction mixture was heated at 120 C. in an oil bath for 18 h. The reaction mixture was cooled to rt, filtered through celite and washed with DCM. The crude material was purified by prep HPLC to yield N-[6-amino-5-(dimethylsulfamoyl)-3,4'-bipyridin-2'-yl]acetamide (0.047 g, 26%). LCMS (AA): m/z=336.0 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00211
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0283; 0285

24
[ 1220220-21-2 ]
C₉H₁₁BrN₂O₂S [ No CAS ]
N-[5-(pyrrolidin-1-ylsulfonyl)-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 120℃; for 18h;Inert atmosphere; Sealed tube;	[00211] <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.127 g, 0.483 mmol), 2-amino-5-bromo-N,N-dimethylpyridine-3-sulfonamide (0.176 g, 0.628 mmol), potassium carbonate (134 mg, 0.966 mmol), 1,4-dioxane:water (4.26 niL, 6:1 mixture) and Pd(dppf)C12 (19.9 mg, 0.024 mmol) were combined in a reaction vial, flushed with nitrogen and sealed. The reaction mixture was heated at 120 C in an oil bath for 18 h. The reaction mixture was cooled to ii, filtered through celite and washed with DCM. The crude material was purified by prep HPLC to yield N-[6-amino-5- (dimethylsulfamoyl)-3,4?-bipyridin-2?-yl]acetamide (0.047 g, 26%).**In Step 2, tetrakis(triphenylphosphine)palladium(0) and cesium carbonate were used instead of Pd(dppf)C12 and potassium carbonate.

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00211; 00212
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0283; 0285-0286

25
[ 113118-81-3 ]
[ 1220220-21-2 ]
N-(5-formyl-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 0.583333h;Inert atmosphere; Sealed tube; Microwave irradiation;	[00211] <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.127 g, 0.483 mmol), 2-amino-5-bromo-N,N-dimethylpyridine-3-sulfonamide (0.176 g, 0.628 mmol), potassium carbonate (134 mg, 0.966 mmol), 1,4-dioxane:water (4.26 niL, 6:1 mixture) and Pd(dppf)C12 (19.9 mg, 0.024 mmol) were combined in a reaction vial, flushed with nitrogen and sealed. The reaction mixture was heated at 120 C in an oil bath for 18 h. The reaction mixture was cooled to ii, filtered through celite and washed with DCM. The crude material was purified by prep HPLC to yield N-[6-amino-5- (dimethylsulfamoyl)-3,4?-bipyridin-2?-yl]acetamide (0.047 g, 26%).***In Step 2, the reaction mixture was heated in the microwave (120 C, 35 mm).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00211; 00212
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0286

26
[ 1220220-21-2 ]
N-(5-bromo-2-methylpyridin-3-yl)-N-methylcyclopropanesulfonamide [ No CAS ]
N-{5-[(cyclopropylsulfonyl)(methyl)amino]-6-methyl-3,4'-bipyridin-2'-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; In 1,4-dioxane; water; at 150℃; for 0.666667h;Microwave irradiation; Inert atmosphere;	[00223] To a microwave vial were added N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin- 2-yl]acetamide (45 mg, 0.17 mmol) and potassium carbonate (125 mg, 0.924 mmol) SiliaCat DPP-Pd (81.5 mg, 0.020 mmol) and 1 ,4-dioxane:water (3.1 mL, 7:1 mixture) The vial was flushed with nitrogen and the reaction was heated in the microwave at 150 C for 40 mm. The reaction mixture was cooled to ii and then filtered through celite and washed with MeOH. The solvent was removed under reduced pressure and the residue was purified by column chromatography to yield N- {5- [(cyclopropylsulfonyl)(methyl)amino]-6-methyl-3,4?-bipyridin-2?-yl}acetamide (37 mg, 77%). LCMS (FA): m/z 361.2 (M+H).
77%	With potassium carbonate; In 1,4-dioxane; water; at 150℃; for 0.666667h;Microwave irradiation; Inert atmosphere;	Step 3: N-{5-[(cyclopropylsulfonyl)(methyl)amino]-6-methyl-3,4'-bipyridin-2'-yl}acetamide To a microwave vial were added <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (45 mg, 0.17 mmol) and potassium carbonate (125 mg, 0.924 mmol) SiliaCat DPP-Pd (81.5 mg, 0.020 mmol) and 1,4-dioxane:water (3.1 mL, 7:1 mixture) The vial was flushed with nitrogen and the reaction was heated in the microwave at 150 C. for 40 min. The reaction mixture was cooled to rt and then filtered through celite and washed with MeOH. The solvent was removed under reduced pressure and the residue was purified by column chromatography to yield N-{5-[(cyclopropylsulfonyl)(methyl)amino]-6-methyl-3,4'-bipyridin-2'-yl}acetamide (37 mg, 77%). LCMS (FA): m/z=361.2 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00223
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0298; 0301

27
[ 1220220-21-2 ]
C₈H₁₂BrN₃O₂S [ No CAS ]
N-{5-[(dimethylsulfamoyl)(methyl)amino]-3,4’-bipyridin-2’-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; XPhos; In 1,4-dioxane; water; at 110℃; for 2h;Microwave irradiation; Inert atmosphere;	[00223] To a microwave vial were added N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin- 2-yl]acetamide (45 mg, 0.17 mmol) and potassium carbonate (125 mg, 0.924 mmol) SiliaCat DPP-Pd (81.5 mg, 0.020 mmol) and 1 ,4-dioxane:water (3.1 mL, 7:1 mixture) The vial was flushed with nitrogen and the reaction was heated in the microwave at 150 C for 40 mm. The reaction mixture was cooled to ii and then filtered through celite and washed with MeOH. The solvent was removed under reduced pressure and the residue was purified by column chromatography to yield N- {5- [(cyclopropylsulfonyl)(methyl)amino]-6-methyl-3,4?-bipyridin-2?-yl}acetamide (37 mg, 77%).In Step 3, conditions used were Pd2(dba)3,,XPhos, KOAc, Dioxane, water (110C, 2h).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00223; 00224
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0302

28
[ 1083325-90-9 ]
[ 1220220-21-2 ]
N-{5-[(dimethylsulfamoyl)amino]-3,4’-bipyridin-2’-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; XPhos; In 1,4-dioxane; water; at 110℃; for 18h;Inert atmosphere; Microwave irradiation;	[00228] N-(5-bromopyridin-3-yl)-3-chloropropane-i-sulfonamide (0.29 g, 0.79 mmol), N-[4-(4,4,5,5- tetramethyl-i,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (0.27 g, 1.03 mmol), [1,1?- bis(diphenylphosphino)ferrocene]dichloropalladium (65 mg, 0.079 mmol) and cesium carbonate (0.77 g, 2.37 mmol) were taken up in 1,4-dioxane (2.16 mL) and water (0.37 mL) under an atmosphere of nitrogen. The reaction mixture was heated at 110C for 18 h. The reaction mixture was cooled toil and water was added and extracted with EtOAc. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated by rotary evaporation. The crude compound was purified by column chromatography to provide N-(5-[(2,4-difluorophenyl)sulfonyl]amino}-6-methyl-3,4?-bipyridin- 2?-yl)acetamide (142 mg, 43%).??Step 2 conditions use Pd2(dba)3 XPhos,KOAC, dioxane, water,1 10C

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00228; 00229
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0306; 0308-0309

29
[ 1220220-21-2 ]
C₁₂H₆BrF₂N₃O₂S [ No CAS ]
N-(6-cyano-5-[(2,4-difluorophenyl)sulfonyl]amino}-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120 - 150℃; for 18h;Inert atmosphere; Microwave irradiation;	[00228] N-(5-bromopyridin-3-yl)-3-chloropropane-i-sulfonamide (0.29 g, 0.79 mmol), N-[4-(4,4,5,5- tetramethyl-i,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (0.27 g, 1.03 mmol), [1,1?- bis(diphenylphosphino)ferrocene]dichloropalladium (65 mg, 0.079 mmol) and cesium carbonate (0.77 g, 2.37 mmol) were taken up in 1,4-dioxane (2.16 mL) and water (0.37 mL) under an atmosphere of nitrogen. The reaction mixture was heated at 110C for 18 h. The reaction mixture was cooled toil and water was added and extracted with EtOAc. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated by rotary evaporation. The crude compound was purified by column chromatography to provide N-(5-[(2,4-difluorophenyl)sulfonyl]amino}-6-methyl-3,4?-bipyridin- 2?-yl)acetamide (142 mg, 43%).Step 2 conditions use K2C03 instead of Cs2CO3 and microwave irradiation ranging from 120-150C

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00228; 00229
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0306; 0308-0309

30
[ 1220220-21-2 ]
C₁₀H₇BrCl₂N₂O₂S₂ [ No CAS ]
N-(5-[(2,5-dichloro-3-thienyl)sulfonyl]amino}-6-methyl-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With methanesulfonic acid(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); potassium carbonate; In 1,4-dioxane; water; at 130℃; for 18h;Microwave irradiation; Inert atmosphere;	[00228] N-(5-bromopyridin-3-yl)-3-chloropropane-i-sulfonamide (0.29 g, 0.79 mmol), N-[4-(4,4,5,5- tetramethyl-i,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (0.27 g, 1.03 mmol), [1,1?- bis(diphenylphosphino)ferrocene]dichloropalladium (65 mg, 0.079 mmol) and cesium carbonate (0.77 g, 2.37 mmol) were taken up in 1,4-dioxane (2.16 mL) and water (0.37 mL) under an atmosphere of nitrogen. The reaction mixture was heated at 110C for 18 h. The reaction mixture was cooled toil and water was added and extracted with EtOAc. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated by rotary evaporation. The crude compound was purified by column chromatography to provide N-(5-[(2,4-difluorophenyl)sulfonyl]amino}-6-methyl-3,4?-bipyridin- 2?-yl)acetamide (142 mg, 43%).Step 2 conditions use XPhosG3; 0.500 M of K3P04, dioxane, microwave irradiation at130 C

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00228; 00229
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0306; 0308-0309

31
[ 1220220-21-2 ]
C₉H₁₂BrN₃O₂S [ No CAS ]
N-[6-methyl-5-(5-methyl-1,1-dioxido-1,2,5-thiadiazolidin-2-yl)-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; ethanol; water; toluene; at 120℃; for 18h;Inert atmosphere; Sealed tube;	[00211] <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.127 g, 0.483 mmol), 2-amino-5-bromo-N,N-dimethylpyridine-3-sulfonamide (0.176 g, 0.628 mmol), potassium carbonate (134 mg, 0.966 mmol), 1,4-dioxane:water (4.26 niL, 6:1 mixture) and Pd(dppf)C12 (19.9 mg, 0.024 mmol) were combined in a reaction vial, flushed with nitrogen and sealed. The reaction mixture was heated at 120 C in an oil bath for 18 h. The reaction mixture was cooled to ii, filtered through celite and washed with DCM. The crude material was purified by prep HPLC to yield N-[6-amino-5- (dimethylsulfamoyl)-3,4?-bipyridin-2?-yl]acetamide (0.047 g, 26%).Final coupling with reagent ad? used Pd(PPh3)4 Na2CO3, EIOH/Tohiene; 120C

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00211; 00256

32
[ 1220220-21-2 ]
3-bromo-5-(methylsulfonyl)pyridine 1-oxide [ No CAS ]
N-{4-[5-(methylsulfonyl)-1-oxidopyridin-3-yl]pyridin-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With potassium carbonate; In 1,4-dioxane; water; at 150℃; for 0.666667h;Microwave irradiation;	[00266] 3-bromo-5-(methylsulfonyl)pyridine 1-oxide (240 mg, 0.19 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (75 mg, 0.29 mmol), K2C03 (132 mg, 0.95 mmol) and SiliaCat DPP-Pd (91 mg, 0.022 mmol) were suspended in dioxane (3.0 mL) and water (0.43 niL). The reaction mixture was heated at 150 C in the microwave for 40 mm. The solvent was removed by rotary evaporation, then the crude compound was purified by colum chromatography followed by prep HPLC to give N-{4-[5-(methylsulfonyl)-1-oxidopyridin-3-yl]pyridin-2-yl}acetamide (10 mg, 17%).LCMS (FA): m/z= 308.1 (M+H).
17%	With potassium carbonate; In 1,4-dioxane; water; at 150℃; for 0.666667h;Microwave irradiation;	Step 2: N-{4-[5-(methylsulfonyl)-1-oxidopyridin-3-yl]pyridin-2-yl}acetamide 3-bromo-5-(methylsulfonyl)pyridine 1-oxide (240 mg, 0.19 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (75 mg, 0.29 mmol), K2CO3 (132 mg, 0.95 mmol) and SiliaCat DPP-Pd (91 mg, 0.022 mmol) were suspended in dioxane (3.0 mL) and water (0.43 mL). The reaction mixture was heated at 150 C. in the microwave for 40 min. The solvent was removed by rotary evaporation, then the crude compound was purified by column chromatography followed by prep HPLC to give N-{4-[5-(methylsulfonyl)-1-oxidopyridin-3-yl]pyridin-2-yl}acetamide (10 mg, 17%). LCMS (FA): m/z=308.1 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00266
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0364; 0366

33
[ 1220220-21-2 ]
(2E)-3-(5-bromopyridin-3-yl)-1-(4-fluorophenyl)prop-2-en-1-one [ No CAS ]
N-{5-[(1E)-3-(4-fluorophenyl)-3-oxoprop-1-en-1-yl]-3,4’-bipyridin-2'-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15.2%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 0.5h;Inert atmosphere; Sealed tube; Microwave irradiation;	[00211] <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.127 g, 0.483 mmol), 2-amino-5-bromo-N,N-dimethylpyridine-3-sulfonamide (0.176 g, 0.628 mmol), potassium carbonate (134 mg, 0.966 mmol), 1,4-dioxane:water (4.26 niL, 6:1 mixture) and Pd(dppf)C12 (19.9 mg, 0.024 mmol) were combined in a reaction vial, flushed with nitrogen and sealed. The reaction mixture was heated at 120 C in an oil bath for 18 h. The reaction mixture was cooled to ii, filtered through celite and washed with DCM. The crude material was purified by prep HPLC to yield N-[6-amino-5- (dimethylsulfamoyl)-3,4?-bipyridin-2?-yl]acetamide (0.047 g, 26%).[00280] The procedure described in Step 2 of Example 5 was followed with the following modification: The reaction was heated in the microwave at 120C for 30 mm to yield N-{5-[(1E)-3-(4- fluorophenyl)-3-oxoprop-1-en-1-yl]-3,4?-bipyridin-2?-yl}acetamide (30 mg, 15.2%). LCMS (FA): m/z 362 (M+H).
15.2%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 0.5h;Inert atmosphere; Sealed tube; Microwave irradiation;	General procedure: Step 2: N-{5-[(1E)-3-(4-fluorophenyl)-3-oxoprop-1-en-1-yl]-3,4?-bipyridin-2?-yl}acetamide (0385) The procedure described in Step 2 of Example 5 was followed with the following modification: The reaction was heated in the microwave at 120 C. for 30 min to yield N-{5-[(1E)-3-(4-fluorophenyl)-3-oxoprop-1-en-1-yl]-3,4?-bipyridin-2?-yl}acetamide (30 mg, 15.2%). LCMS (FA): m/z=362 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00211; 00280
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0283; 0285; 0383; 0385

34
[ 1092580-97-6 ]
[ 1220220-21-2 ]
2'-acetamido-6-amino-N,N-dimethyl-3,4’-bipyridine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53.2%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 130℃; for 0.5h;Inert atmosphere; Microwave irradiation;	[00283] A microwave tube was charged with <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (153 mg, 0.582 mmol), 2-amino-5-bromo-N,N-dimethylnicotinamide (115 mg, 0.47 1 mmol) and Pd(dppf)C12 (24 mg, 0.030 mmol). 1,4-dioxane (3.7 niL, 47 mmol) and potassium carbonate (2 M in water; 0.471 mL, 0.942 mmol) were added. The tube was purged with nitrogen and heated at 130 C for 30 mm in the microwave. The mixture was partitioned between EtOAc and water. The aqueous layer was further extracted with EtOAc and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude material was purified by prep HPLC to yield 2?-acetamido-6-amino-N,N-dimethyl-3,4?-bipyridine-5-carboxamide (75 mg, 53.2%). LCMS (AA):m/z 300.1 (M+H).
53.2%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 130℃; for 0.5h;Inert atmosphere; Microwave irradiation;	Step 2: 2'-acetamido-6-amino-N,N-dimethyl-3,4'-bipyridine-5-carboxamide A microwave tube was charged with <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (153 mg, 0.582 mmol), 2-amino-5-bromo-N,N-dimethylnicotinamide (115 mg, 0.471 mmol) and Pd(dppf)Cl2 (24 mg, 0.030 mmol). 1,4-dioxane (3.7 mL, 47 mmol) and potassium carbonate (2 M in water; 0.471 mL, 0.942 mmol) were added. The tube was purged with nitrogen and heated at 130 C. for 30 min in the microwave. The mixture was partitioned between EtOAc and water. The aqueous layer was further extracted with EtOAc and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude material was purified by prep HPLC to yield 2'-acetamido-6-amino-N,N-dimethyl-3,4'-bipyridine-5-carboxamide (75 mg, 53.2%). LCMS (AA): m/z=300.1 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00283
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0387; 0389

35
[ 1220220-21-2 ]
5-bromo-N-(2,4-difluorophenyl)-N,2-dimethylnicotinamide [ No CAS ]
2’-acetamido-N-(2,4-difluorophenyl)-N,6-dimethyl-3,4’-bipyridine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; toluene;Microwave irradiation;	[00283] A microwave tube was charged with <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (153 mg, 0.582 mmol), 2-amino-5-bromo-N,N-dimethylnicotinamide (115 mg, 0.47 1 mmol) and Pd(dppf)C12 (24 mg, 0.030 mmol). 1,4-dioxane (3.7 niL, 47 mmol) and potassium carbonate (2 M in water; 0.471 mL, 0.942 mmol) were added. The tube was purged with nitrogen and heated at 130 C for 30 mm in the microwave. The mixture was partitioned between EtOAc and water. The aqueous layer was further extracted with EtOAc and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude material was purified by prep HPLC to yield 2?-acetamido-6-amino-N,N-dimethyl-3,4?-bipyridine-5-carboxamide (75 mg, 53.2%).Step 2 conditions use Pd(PPh3)4, 1.0 M Na2CO3toluene, and EtOH under microwave irradiation

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00283; 00284
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0390

36
[ 1220220-21-2 ]
[ 15862-47-2 ]
N-(2’-acetamido-3,4’-bipyridin-5-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33.3%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 18h;Inert atmosphere; Sealed tube;	[00288] To a reaction vial were added<strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.142 g, 0.544 mmol)), N-(5-bromopyridin-3-yl)benzamide (0.196 g, 0.707 mmol), potassium carbonate (150 mg, 1.09 mmol) and dioxane-water(6:1 mixture of 1,4-dioxane:water; 4.80 niL). The mixture was flushed with argon and Pd(dppf)C12 (22.4 mg, 0.027 mmol) was added. The reaction was sealed and heated at 120C in an oil bath for 18 h. The reaction was filtered through celite and the celite was washed with DCM. The filtrate was concentrated and the residue was purified by column chromatography to yield N-(2?-acetamido-3,4?-bipyridin-5-yl)benzamide (60 mg, 33.3%). LCMS (FA): m/z=333.1 (M+H).
33.3%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 18h;Inert atmosphere;	Step 2: N-(2'-acetamido-3,4'-bipyridin-5-yl)benzamide To a reaction vial were added <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.142 g, 0.544 mmol)), N-(5-bromopyridin-3-yl)benzamide (0.196 g, 0.707 mmol), potassium carbonate (150 mg, 1.09 mmol) and dioxane-water(6:1 mixture of 1,4-dioxane:water; 4.80 mL). The mixture was flushed with argon and Pd(dppf)Cl2 (22.4 mg, 0.027 mmol) was added. The reaction was sealed and heated at 120 C. in an oil bath for 18 h. The reaction was filtered through celite and the celite was washed with DCM. The filtrate was concentrated and the residue was purified by column chromatography to yield N-(2'-acetamido-3,4'-bipyridin-5-yl)benzamide (60 mg, 33.3%). LCMS (FA): m/z=333.1 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00288
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0395; 0397

37
[ 1220220-21-2 ]
5-bromo-N-(2,4-difluorophenyl)-2-(dimethylamino)-N-methylnicotinamide [ No CAS ]
2’-acetamido-N-(2,4-difluorophenyl)-6-(dimethylamino)-N-methyl-[3,4’-bipyridine]-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 140℃; for 0.5h;Microwave irradiation;	[00292] To a solution of N-[4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (164 mg, 0.628 mmol) in 1,4-dioxane (6.3 niL) and water (0.2 mL, 9 mmol) were added 5-bromo-N-(2,4- difluorophenyl)-2-(dimethylamino)-N-methylnicotinamide (155 mg, 0.418 mmol), tetrakis (triphenylphosphine) palladium (32.0 mg, 0.026 mmol) and cesium carbonate (409 mg, 1.26 mmol). The reaction mixture was heated at 140 C for 30 mm under microwave irradiation. Then, the reaction mixture was diluted with EtOAc. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude material was purified by prep HPLC to yield 2?-acetamido-N-(2,4- difluorophenyl)-6-(dimethylamino)-N-methyl-[3,4?-bipyridine]-S-carboxamide (91 mg, 51.0%). LCMS (FA): m/z 426.5 (M+H).
51.0%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 140℃; for 0.5h;Microwave irradiation;	Step 3: 2'-Acetamido-N-(2,4-difluorophenyl)-6-(dimethylamino)-N-methyl-[3,4'-bipyridine]-5-carboxamide To a solution of <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (164 mg, 0.628 mmol) in 1,4-dioxane (6.3 mL) and water (0.2 mL, 9 mmol) were added 5-bromo-N-(2,4-difluorophenyl)-2-(dimethylamino)-N-methylnicotinamide (155 mg, 0.418 mmol), tetrakis (triphenylphosphine) palladium (32.0 mg, 0.026 mmol) and cesium carbonate (409 mg, 1.26 mmol). The reaction mixture was heated at 140 C. for 30 min under microwave irradiation. Then, the reaction mixture was diluted with EtOAc. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude material was purified by prep HPLC to yield 2'-acetamido-N-(2,4-difluorophenyl)-6-(dimethylamino)-N-methyl-[3,4'-bipyridine]-5-carboxamide (91 mg, 51.0%). LCMS (FA): m/z=426.5 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00292
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0399; 0402

38
[ 90902-83-3 ]
[ 1220220-21-2 ]
bicyclo[1.1.1]pentan-1-amine hydrochloride [ No CAS ]
[ 544-97-8 ]
N-[5-(bicyclo[1.1.1]pent-1-ylsulfamoyl)-6-methyl-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]
N-(6-methyl-5-sulfamoyl-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%; 26%		[00391] To 2-bromo-3-amino-5-chloropyridine (5.00 g, 24.1 mmol) in a 100 ml flask cooled in ice bath was added portion wise 12.0 M of HC1 (24.2 niL). The mixture was allowed to stir at ii for 15 mm. This was cooled in ice/acetone bath (?- -8 C). A solution of sodium nitrite (2.00 g, 28.9 mmol) in water (7.82 mL, 434 mmol) was added over 45 mm. The resulting slurry was allowed to stir for 30 mm. A solution of 502 in water was prepared the night before by adding thionyl chloride (4.40 mL, 60.2 mmol) over 30 mm. to water (26.0 mL, 1440 mmol) cooled in ice/bath. The mixture was then allowed to stir and to warm at ii overnight. To that solution was added cuprous monochloride (47 mg, 0.47 mmol). The resulting yellow solution was cooled in ice/acetone at -8 C. The diazotized mixture described earlier maintained at -8 C(acetone/ice) was then added portionwise with pipette over 30mm. The mixture was then allowed to stir at 0 C for 75 mm. The mixture was extracted with ether twice. The combined ether extracts were washed with brine, dried over Na2SO4 and concentrated. The oily residue was dried under high vacuum overnight to give a 1:2 mixture (approximate based on lii NMR (400 MHz, CDC13)) of 2- bromo-5-chloropyridine-3-sulfonyl chloride and 2,5-dichloropyridine-3-sulfonyl chloride as a red oil (ig of crude material). The product was used in the next step without further purification.[00392] To a solution 2-bromo-5-chloropyridine-3-sulfonyl chloride and 2,5-dichloropyridine-3- sulfonyl chloride(i.0 g, 3.8 mmol) in 1,4-dioxane (8.6 mL) and pyridine (1.10 mL) at ii was added bicyclo[i.i.i]pentan-i-amine hydrochloride salt (0.527 g, 4.41 mmol) portion wise. The mixture was allowed to stir at ii for 2 h. Water (2 mL) was added and the mixture was allowed to stir for a few mm. The reaction mixture was diluted with water (40m1) and acidified to pH 4 with 0.5 citric acid and was extracted with EtOAc (2x40m1). The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by column chromatography using to give a 1:2 mixture of N-(bicyclo[i .1. i]pent-i-yl)-2-bromo-5-chloropyridine-3-sulfonamide and N(bicyclo[i.i.i]pent-i-yl)-2,5-dichloropyridine-3-sulfonamide as a light yellow solid (339 mg, 85% yield).[00393] To the mixture obtained in Step 2 of N-(bicyclo[i. 1. i]pent-i-yl)-2-bromo-5-chloropyridine- 3-sulfonamide, N-(bicyclo[i .1. i]pent-i-yl)-2,5-dichloropyridine-3-sulfonamide (327 mg, 1.07 mmol) and [i,i?-bis(diphenylphosphino)ferrocene]dichloropalladium(II),complex with DCM (1:1) (54 mg, 0.066 mmol) in 1 ,4-dioxane (7.5 mL) was added with caution dimethylzinc in toluene( 2.0 M, 0.88 mL, 1.8 mmol) under an atmosphere of nitrogen. After a few mm the mixture was heated to 75 C then allowed to stir for 90 mm. The reaction mixture was allowed to cool to ii and then added to water. The resulting solution was acidified with 0.5% citric acid and was extracted with EtOAc twice. The organic solutions were combined, washed with brine, dried over Na2504, filtered and concentrated. The residue was purified by column chromatographyto give N-(bicyclo[i. 1. i]pent-i-yl)-5-chloro-2-methylpyridine-3- sulfonamide (85 mg, 28%).[00394] A microwave tube was charged with N-(hicyclo[i. 1. i]pent-i-yl)-5-chloro-2-methylpyridine- 3-sulfonamide (83 mg, 0.30 mmol), N-[4-(4,4,5,5-tetramethyl-i,3,2-dioxaborolan-2-yl)pyridin-2- yl]acetamide (98.6 mg, 0.376 mmol), 2-dicyclohexylphosphino-2?,4?,6?-tri-i-propyl-i,i?-biphenyl (14 mg, 0.029 mmol), tris(dba)dipalladium(0) (8.3 mg, 0.0092 mmol) and potassium acetate (89 mg, 0.91 mmol). The tube was purged with nitrogen and 1 ,4-dioxane (2.4 niL) was added. The reaction mixture was allowed to stir for 2 mm and water (0.51 niL) was added. The tube was purged with nitrogen three times, sealed, and was heated at 110C in oil bath for 1.5 h. After the reaction mixture was allowed to cool to ii, the mixture was diluted with EtOAc (25m1) and water (15m1). The aqueous solution was separated and further extracted with EtOAc (1 5m1). The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The products were purified by column chromatography using 0- 3% MeOH/DCM over 25mm. to give N-[5-(bicyclo[i. i.i]pent-i-ylsulfamoyl)-6-methyl-3,4?-bipyridin-2?- yl]acetamide (1-418) (25 mg, 22%) as a white solid. LCMS (FA): m/z 373.4 (M+I-I). 1H NMR (400 MFIz, DMSO-d6) 6 10.68 (s, 1H), 9.12 (s, 1H), 9.05 (d, J= 2.2 Hz, 1H), 8.44-8.47 (m, 2H), 8.39 (d, J= 2.2 Hz, 1H), 7.5 1-7.55 (m, 1H), 2.83 (s, 3H), 2.31 (s, 1H), 2.14 (s, 3H), 1.77 (s, 6H). Further elution using6% MeOH/DCM gave by product N-(6-methyl-5-sulfamoyl-3,4?-bipyridin-2?-yl)acetamide (1-395) (24 mg, 26%) as a white solid. LCMS (FA): m/z 307.4 (M+H). ?H NMR (400 MFIz, DMSO-d6) 6 10.68 (s, 1H), 8.99 (d, J= 2.2 Hz, 1H), 8.44-8.47 (m, 1H), 8.43 -8.39 (m, 2H), 7.76 (s, 2H), 7.48-7.52 (m, 1H),2.85 (s, 3H), 2.14 (s, 3H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00391; 00392; 00393; 00394

39
[ 1220220-21-2 ]
N-(bicyclo[1.1.1]pent-1-yl)-5-bromo-2-(dimethylamino)nicotinamide [ No CAS ]
2'-acetamido-N-(bicyclo[1.1.1]pent-1-yl)-6-(dimethylamino)-3,4'-bipyridine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 130℃; for 0.5h;Inert atmosphere; Microwave irradiation;	[00295] To a vial were added N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2- yl]acetamide (198 mg, 0.75 mmol) and N-(bicyclo[1 .1. 1]pent-1-yl)-5-bromo-2- (dimethylamino)nicotinamide (0.195 g, 0.629 mmol), Pd(dppf)C12, complex with DCM (1:1)(32 mg, 0.039 mmol), 2.0 M potassium carbonate in water (0.63 mL) and 1,4-dioxane (4.9 niL). The vial was thoroughly flushed with N2 and then subjected to microwave irradiation at 130 C for 30 mm. The reaction mixture was partitioned into EtOAc and water. The aqueous solutions were extracted twice. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give 2?-acetamido-N-(bicyclo[l .1. 1]pent-1-yl)-6- (dimethylamino)- 3,4?-bipyridine-S-carboxamide 1-283 (0.20 g, 80%) LCMS (FA): m/z 366.2 (M+1).
80%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 130℃; for 0.5h;Inert atmosphere; Microwave irradiation;	Step 2: 2'-Acetamido-N-(bicyclo[1.1.1]pent-1-yl)-6-(dimethylamino)-3,4'-bipyridine-5-carboxamide To a vial were added <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (198 mg, 0.75 mmol) and N-(bicyclo[1.1.1]pent-1-yl)-5-bromo-2-(dimethylamino)nicotinamide (0.195 g, 0.629 mmol), Pd(dppf)Cl2, complex with DCM (1:1) (32 mg, 0.039 mmol), 2.0 M potassium carbonate in water (0.63 mL) and 1,4-dioxane (4.9 mL). The vial was thoroughly flushed with N2 and then subjected to microwave irradiation at 130 C. for 30 min. The reaction mixture was partitioned into EtOAc and water. The aqueous solutions were extracted twice. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give 2'-acetamido-N-(bicyclo[1.1.1]pent-1-yl)-6-(dimethylamino)-3,4'-bipyridine-5-carboxamide I-283 (0.20 g, 80%) LCMS (FA): m/z=366.2 (M+1).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00295
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0405; 0407

40
[ 1220220-21-2 ]
N-(bicyclo[1.1.1]pent-1-yl)-5-bromo-2-(dimethylamino)-N-methylnicotinamide [ No CAS ]
2’-acetamido-N-(bicyclo[1.1.1]pent-1-yl)-N-methyl-6-(methylamino)-3,4’-bipyridine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 0.5h;Inert atmosphere; Microwave irradiation;	[00300] To a vial were added (5-(bicyclo[1.1.1]pent-1-yl(methyl)carbamoyl)-6- (dimethylamino)pyridin-3-yl)boronic acid (65 mg, 0.22 mmol), N-(4-chloropyridin-2-yl)-2- methylpyrimidin-4-amine (59 mg, 0.27 mmol), XPhos (3.3 mg, 0.007 mmol), XPhosG3 (6.4 mg, 0.007 mmol), 0.5 M potassium phosphate in water (0.91 niL, 0.45 mmol) and 1,4-dioxane (0.45 niL). The vial was thoroughly flushed with N2 and then was subjected to microwave irradiation at 120C for 30 mm. The reaction mixture was partitioned into EtOAc and water. The aqueous solution was extracted twice. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude compound was purified by column chromatography to give N(bicyclo[1.1. 1]pent-1-yl)-6-(dimethylammno)-N-methyl-2?-((2-methylpyrimidin-4-yl)ammno)- 3,4?- bipyridine-5-carboxamide 1-306 (0.042 g, 44%) with 90% purity.* Step 5 conditions use Pd(dppf)C12 and K2C03 instead of XPhosG3/XPhos and K3P04

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00300; 00301

41
[ 875781-17-2 ]
[ 1220220-21-2 ]
N-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.2%	With potassium phosphate; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); In water; 1,2-dichloro-ethane; at 150℃; for 1h;Microwave irradiation;	[00326] A mixture of 5-bromo-1H-pyrazolo[3,4-b]pyridine (0.100 g, 0.505 mmol) , N-(4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (0.199 g, 0.758 mmol), amphosdichloropalladium(II) (0.0718 g, 0.101 mmol) and potassium phosphate (0.323 g, 1.52 mmol) was allowed to stir in water (0.27 mL) and DME (4.6 mL) and heated in the microwave at 150C for 60 mm. The reaction mixture was partitioned between water and EtOAc and the organic layer was washed with brine. The aqueous layer was further extracted with a DCM/MeOH mixture. The combined all organic layers were dried over magnesium sulfate, filtered and concentrated by rotary evaporation. Added MeOH and filtered to remove solids and concentrated the supernatant by rotary evaporation. Purified by prep HPLC to yield N-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-yl]acetamide (1.5 mg, 1.2%). LCMS(FA): m/z 254.4 (M+H).
1.2%	With potassium phosphate; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); In 1,2-dimethoxyethane; water; at 150℃; for 1h;Microwave irradiation;	Example 33 N-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-yl]acetamide I-189 A mixture of 5-bromo-1H-pyrazolo[3,4-b]pyridine (0.100 g, 0.505 mmol), <strong>[1220220-21-2]N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide</strong> (0.199 g, 0.758 mmol), amphosdichloropalladium(II) (0.0718 g, 0.101 mmol) and potassium phosphate (0.323 g, 1.52 mmol) was allowed to stir in water (0.27 mL) and DME (4.6 mL) and heated in the microwave at 150 C. for 60 min. The reaction mixture was partitioned between water and EtOAc and the organic layer was washed with brine. The aqueous layer was further extracted with a DCM/MeOH mixture. The combined all organic layers were dried over magnesium sulfate, filtered and concentrated by rotary evaporation. Added MeOH and filtered to remove solids and concentrated the supernatant by rotary evaporation. Purified by prep HPLC to yield N-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-2-yl]acetamide (1.5 mg, 1.2%). LCMS(FA): m/z=254.4 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00326
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0448-0449

42
[ 1220220-21-2 ]
C₁₃H₁₀BrClF₂N₂O₂S [ No CAS ]
N-(6-chloro-5-[(2,4-difluorophenyl)sulfonyl]amino}-4-ethyl-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 140 - 150℃;Inert atmosphere; Microwave irradiation;	[00328] N-(5-Bromo-2-chloro-4-methylpyridin-3-yl)-2,4-difluorobenzenesulfonamide (6.40 g, 16.1 mmol), 2-methyl-N-[4-(4,4,5,5-tetramethyl-i,3,2-dioxaborolan-2-yl)pyridin-2-yl]pyrimidin-4-amine (6.0 g, 19 mmol) and Pd(dppf)C12 (431 mg, 0.524 mmol) were combined in a round bottomed flask equipped with a stirbar. Degassed i,4-dioxane (125 niL) and degassed potassium carbonate in water (1.0 M, 32.2 niL, 32.2 mmol) were added. The flask was evacuated and refilled with argon three times and then the reaction mixture was allowed to stir overnight at 105 C under an argon atmosphere. The reaction was allowed to cool to ii then filtered through a fritted funnel The filtrate was concentrated to ?-one-half volume and then was slowly poured into stirring saline solution (750 mL). The resulting mixture was stirred and the pH was adjusted to 6.5 via the slow addition of iN HC1. The precipitate which formed was collected by filtration and air-dried to leave a gray solid. The crude product was purified by column chromatography to provide N-{6-chloro-4-methyl-2?-[(2-methylpyrimidin-4-yl)amino]-3,4?-bipyridin-5- yl}-2,4-difluorobenzenesulfonamide 1-299 (4.3 g, 53%) as a white powder.**In step 2, microwave irradiation was used (140-150 C)

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00328; 00329
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0450; 0452-0453

43
[ 1220220-21-2 ]
N-(5-bromo-2,4-dimethylpyridin-3-yl)-2,4-difluorobenzenesulfonamide [ No CAS ]
N-(5-[(2,4-difluorophenyl)sulfonyl]amino}-4,6-dimethyl-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 105℃;Inert atmosphere;	[00328] N-(5-Bromo-2-chloro-4-methylpyridin-3-yl)-2,4-difluorobenzenesulfonamide (6.40 g, 16.1 mmol), 2-methyl-N-[4-(4,4,5,5-tetramethyl-i,3,2-dioxaborolan-2-yl)pyridin-2-yl]pyrimidin-4-amine (6.0 g, 19 mmol) and Pd(dppf)C12 (431 mg, 0.524 mmol) were combined in a round bottomed flask equipped with a stirbar. Degassed i,4-dioxane (125 niL) and degassed potassium carbonate in water (1.0 M, 32.2 niL, 32.2 mmol) were added. The flask was evacuated and refilled with argon three times and then the reaction mixture was allowed to stir overnight at 105 C under an argon atmosphere. The reaction was allowed to cool to ii then filtered through a fritted funnel The filtrate was concentrated to ?-one-half volume and then was slowly poured into stirring saline solution (750 mL). The resulting mixture was stirred and the pH was adjusted to 6.5 via the slow addition of iN HC1. The precipitate which formed was collected by filtration and air-dried to leave a gray solid. The crude product was purified by column chromatography to provide N-{6-chloro-4-methyl-2?-[(2-methylpyrimidin-4-yl)amino]-3,4?-bipyridin-5- yl}-2,4-difluorobenzenesulfonamide 1-299 (4.3 g, 53%) as a white powder.*In step 2, Cs2CO3 was used instead of K2C03

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00328; 00329
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0450; 0452-0453

44
[ 1220220-21-2 ]
C₁₀H₁₄BrClN₂O₂S [ No CAS ]
N-[5-(tert-butylsulfamoyl)-6-chloro-4-methyl-3,4’-bipyndin-2-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Inert atmosphere; Sealed tube; Microwave irradiation;	[00383] A partial suspension of 5-bromo-2-chloro-N-cyclobutylpyridine-3-sulfonamide (0.050 g, 0.15 mmol) and 2-methyl-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]pyrimidin-4-amine (0.052 g, 0.166 mmol) in 1,4-dioxane (2.0 niL) was treated with potassium carbonate (0.042 g, 0.30 mmol) in water (0.20 mL) and purged with nitrogen gas. Pd(dppf)C12 (40 mg, 0.05 mmol) was added and the mixture was allowed to stir in a sealed tube at 100 C for 0.5 h. The solvents were evaporated under reduced pressure and the residue was diluted with water and the precipitate collected. The crude product was purified by column chromatography to give 6-chloro-N-cyclobutyl-2?-((2-methylpyrimidin-4- yl)amino)-[3,4?-bipyridine]-S-sulfonamide 1-2 15 (30 mg, 46%).* Step 2: Cs2CO3 was used instead of K2C03, and microwave irradiation was used instead ofconventional heating

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00383; 00384
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0531

45
[ 1220220-21-2 ]
C₁₂H₉ClF₂N₂O₂S [ No CAS ]
N-(5-(N-(2,4-difluorophenyl)sulfamoyl)-6-methyl-[3,4’-bipyridin]-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; XPhos; In 1,4-dioxane; water; at 110℃;	[00383] A partial suspension of 5-bromo-2-chloro-N-cyclobutylpyridine-3-sulfonamide (0.050 g, 0.15 mmol) and 2-methyl-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]pyrimidin-4-amine (0.052 g, 0.166 mmol) in 1,4-dioxane (2.0 niL) was treated with potassium carbonate (0.042 g, 0.30 mmol) in water (0.20 mL) and purged with nitrogen gas. Pd(dppf)C12 (40 mg, 0.05 mmol) was added and the mixture was allowed to stir in a sealed tube at 100 C for 0.5 h. The solvents were evaporated under reduced pressure and the residue was diluted with water and the precipitate collected. The crude product was purified by column chromatography to give 6-chloro-N-cyclobutyl-2?-((2-methylpyrimidin-4- yl)amino)-[3,4?-bipyridine]-S-sulfonamide 1-2 15 (30 mg, 46%).?Step 2: Pd2(dba)3, Xphos, KOAc/water, dioxane, 110 C

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00383; 00384
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0531

46
[ 1220220-21-2 ]
C₁₁H₁₃BrN₂O₃S [ No CAS ]
N-[5-(bicyclo[1.1.1]pent-1-ylsulfamoyl)-6-methoxy-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Inert atmosphere; Sealed tube;	[00383] A partial suspension of 5-bromo-2-chloro-N-cyclobutylpyridine-3-sulfonamide (0.050 g, 0.15 mmol) and 2-methyl-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]pyrimidin-4-amine (0.052 g, 0.166 mmol) in 1,4-dioxane (2.0 niL) was treated with potassium carbonate (0.042 g, 0.30 mmol) in water (0.20 mL) and purged with nitrogen gas. Pd(dppf)C12 (40 mg, 0.05 mmol) was added and the mixture was allowed to stir in a sealed tube at 100 C for 0.5 h. The solvents were evaporated under reduced pressure and the residue was diluted with water and the precipitate collected. The crude product was purified by column chromatography to give 6-chloro-N-cyclobutyl-2?-((2-methylpyrimidin-4- yl)amino)-[3,4?-bipyridine]-S-sulfonamide 1-2 15 (30 mg, 46%).Step 2: Cs2CO3 was used instead of K2C03

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00383; 00384
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0531

47
[ 1220220-21-2 ]
C₁₃H₁₀BrF₃N₂O₃S [ No CAS ]
N-(6-methoxy-5-[3-(trifluoromethyl)phenyl]sulfamoyl}-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 0.5h;Inert atmosphere; Sealed tube; Microwave irradiation;	[00383] A partial suspension of 5-bromo-2-chloro-N-cyclobutylpyridine-3-sulfonamide (0.050 g, 0.15 mmol) and 2-methyl-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]pyrimidin-4-amine (0.052 g, 0.166 mmol) in 1,4-dioxane (2.0 niL) was treated with potassium carbonate (0.042 g, 0.30 mmol) in water (0.20 mL) and purged with nitrogen gas. Pd(dppf)C12 (40 mg, 0.05 mmol) was added and the mixture was allowed to stir in a sealed tube at 100 C for 0.5 h. The solvents were evaporated under reduced pressure and the residue was diluted with water and the precipitate collected. The crude product was purified by column chromatography to give 6-chloro-N-cyclobutyl-2?-((2-methylpyrimidin-4- yl)amino)-[3,4?-bipyridine]-S-sulfonamide 1-2 15 (30 mg, 46%).Step 2: microwave irradiation was used instead of conventional heating

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00383; 00384
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0531

48
[ 1220220-21-2 ]
N-(6-chloro[1,2,4]triazolo[1,5-a]pyridin-8-yl)-2,4-difluorobenzenesulfonamide [ No CAS ]
N-[4-(8-[(2,4-difluorophenyl)sulfonyl]amino}[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-2-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%	With potassium phosphate; methanesulfonic acid(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); XPhos; In 1,4-dioxane; water; at 120 - 130℃; for 0.833333h;Inert atmosphere; Microwave irradiation;	[00398] A mixture of N-(6-chloro[1,2,4]triazolo[1 ,5-a]pyridin-8-yl)-2,4-difluorobenzenesulfonamide (0.060 g, 0.17 mmol) , <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.046 g, 0.17 mmol) , (2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?- biphenyl)]palladium(II) methanesulfonate (8.19 mg, 0.0087 mmol) and 2-dicyclohexylphosphino-2?,4?,6?- tri-i-propyl-1,1?-biphenyl (8.30 mg, 0.0 17 mmol) were placed in a microwave vial. The vessel was evacuated and backfilled with argon 3 times. 1,4-Dioxane (1.36 mL) and potassium phosphate (0.050 M in water, 0.696 niL, 0.348 mmol) was added. The mixture was subjected to microwave irradiation at 130C for 30mm. Additional portions of N-[4-(4,4,5,5-tetramethyl-i,3,2-dioxaborolan-2-yl)pyridin-2- yl]acetamide (0.091 g, 0.35 mmol), (2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-i,i?-biphenyl)[2-(2?- ammno-i,i?-biphenyl)]palladium(II) methanesulfonate (8.0 mg, 0.0085 mmol), 2-dicyclohexylphosphino- 2?,4?,6?-tri-i-propyl-i,i?-biphenyl(8.0 mg, 0.017 mmol) and potassium phosphate (0.50 M in water, 1.00 niL) were added and the mixture was allowed to stir at 120 C for another 20 mm. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography to give N-[4-(8- [(2,4-difluorophenyl)sulfonyl]amino} [i,2,4]triazolo[i ,5-a]pyridin-6-yl)pyridin-2-yl]acetamide 1-340 (7 mg, 9%) as a white solid. LCMS (FA): m/z 444.8 (M+H). in NMR (400 MFIz, DMSO-d6) 6 i0.70(s, in), 9.25(s, in), 8.55(m, in), 8.40(d, J=5.6, in), 8.38 (m, in), 8.03 (dd, Ji=6.4, J2=8.4, 2n), 7.70(m, in), 7.50(d, J=5.6, in), 7.23(t, Ji=7.6, J2=iO, in), 2.15 (s, 31-I).
9%	With potassium phosphate; methanesulfonic acid(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); XPhos; In 1,4-dioxane; water; at 120 - 130℃; for 0.833333h;Microwave irradiation; Inert atmosphere;	Step 4: N-[4-(8-[(2,4-difluorophenyl)sulfonyl]amino}[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-2-yl]acetamide A mixture of N-(6-chloro[1,2,4]triazolo[1,5-a]pyridin-8-yl)-2,4-difluorobenzenesulfonamide (0.060 g, 0.17 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.046 g, 0.17 mmol), (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (8.19 mg, 0.0087 mmol) and 2-dicyclohexylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl (8.30 mg, 0.017 mmol) were placed in a microwave vial. The vessel was evacuated and backfilled with argon 3 times. 1,4-Dioxane (1.36 mL) and potassium phosphate (0.050 M in water, 0.696 mL, 0.348 mmol) was added. The mixture was subjected to microwave irradiation at 130 C. for 30 min Additional portions of <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.091 g, 0.35 mmol), (2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (8.0 mg, 0.0085 mmol), 2-dicyclohexylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl (8.0 mg, 0.017 mmol) and potassium phosphate (0.50 M in water, 1.00 mL) were added and the mixture was allowed to stir at 120 C. for another 20 min. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography to give N-[4-(8-[(2,4-difluorophenyl)sulfonyl]amino}[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-2-yl]acetamide I-340 (7 mg, 9%) as a white solid. LCMS (FA): m/z=444.8 (M+H). 1H NMR (400 MHz, DMSO-d6) delta 10.70 (s, 1H), 9.25 (s, 1H), 8.55 (m, 1H), 8.40(d, J=5.6, 1H), 8.38 (m, 1H), 8.03 (dd, J1=6.4, J2=8.4, 2H), 7.70 (m, 1H), 7.50(d, J=5.6, 1H), 7.23(t, J1=7.6, J2=10, 1H), 2.15 (s, 3H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00398
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0547; 0551

49
[ 625-92-3 ]
[ 1220220-21-2 ]
N-(5-bromo-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 140℃; for 0.5h;Microwave irradiation;	[00399] A mixture of 3,5-dibromopyridine (412 mg, 1.74 mmol), N-[4-(4,4,5,5-tetramethyl- i,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (520 mg, 2.00 mmol), Cs2CO3 (1.30 g, 4.00 mmol) and Pd(PPh3)4 (100 mg, 0.087 mmol) in i,4-dioxane (10.0 mL) and water (2.0 niL) was subjected to microwave irradiation for 30 mm at 140C. The reaction mixture was allowed to cool to ii and diluted with DCM. The mixture was extracted with DCM and washed with water, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography to provide N-(5-bromo-3,4?- bipyridin-2?-yl)acetamide (210 mg, 41%). LCMS (FA): m/z 292.i(M+n).
41%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 140℃; for 0.5h;Microwave irradiation;	Step 1: N-(5-bromo-3,4'-bipyridin-2'-yl)acetamide A mixture of 3,5-dibromopyridine (412 mg, 1.74 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (520 mg, 2.00 mmol), Cs2CO3 (1.30 g, 4.00 mmol) and Pd(PPh3)4 (100 mg, 0.087 mmol) in 1,4-dioxane (10.0 mL) and water (2.0 mL) was subjected to microwave irradiation for 30 min at 140 C. The reaction mixture was allowed to cool to rt and diluted with DCM. The mixture was extracted with DCM and washed with water, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography to provide N-(5-bromo-3,4'-bipyridin-2'-yl)acetamide (210 mg, 41%). LCMS (FA): m/z=292.1 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00399
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0552-0553

50
[ 1220220-21-2 ]
2-(5-bromopyridin-3-yl)-6-methyl-1,2,6-thiadiazinane 1,1-dioxide [ No CAS ]
N-[5-(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 0.333333h;Microwave irradiation;	[00403] To 2-(5-bromopyridin-3-yl)-6-methyl-1,2,6-thiadiazinane 1,1-dioxide (0.108 g, 0.353 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.104 g, 0.395 mmol), and tetrakis(triphenylphosphine)palladium(0) (34.2 mg, 0.0296 mmol) in a mixture of ethanol (1.30 mL) and toluene (1.30 niL) was added sodium carbonate (1.00 M in water, 0.44 niL, 0.44 mmol). The reaction mixture was subjected to microwave irradiation at 120 C for 20 mm. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography to give N-[5-(6-methyl-i,i- dioxido-i,2,6-thiadiazinan-2-yl)-3,4?-bipyridin-2?-yl]acetamide 1-452 as a white solid (58mg, 50%). %). LCMS (FA): m/z 362.2 (M+H). in NEVER (400 JVEFIz, DMSO-d6) 6 i0.68(s, lI-I), 8.82(s, lI-I), 8.67(s, in), 8.43(d, J=5.2, in), 8.39 (s, in), 8.01 (s, in), 7.49 (d, J=5.2, in), 3.84 (dd, Ji=5.2, J2=5.2, 2n), 3.63 (dd, Ji=5.2, J2=5.2, 2n), 2.92 (s, 3n), 2.13 (s, 3n), i.96(m, 2n).
50%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 0.333333h;Microwave irradiation;	Step 3: N-[5-(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)-3,4'-bipyridin-2'-yl]acetamide To 2-(5-bromopyridin-3-yl)-6-methyl-1,2,6-thiadiazinane 1,1-dioxide (0.108 g, 0.353 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.104 g, 0.395 mmol), and tetrakis(triphenylphosphine)palladium(0) (34.2 mg, 0.0296 mmol) in a mixture of ethanol (1.30 mL) and toluene (1.30 mL) was added sodium carbonate (1.00 M in water, 0.44 mL, 0.44 mmol). The reaction mixture was subjected to microwave irradiation at 120 C. for 20 min. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography to give N-[5-(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)-3,4'-bipyridin-2'-yl]acetamide I-452 as a white solid (58 mg, 50%). %). LCMS (FA): m/z=362.2 (M+H). 1H NMR (400 MHz, DMSO-d6) delta 10.68 (s, 1H), 8.82 (s, 1H), 8.67 (s, 1H), 8.43(d, J=5.2, 1H), 8.39 (s, 1H), 8.01 (s, 1H), 7.49 (d, J=5.2, 1H), 3.84 (dd, J1=5.2, J2=5.2, 2H), 3.63 (dd, J1=5.2, J2=5.2, 2H), 2.92 (s, 3H), 2.13 (s, 3H), 1.96 (m, 2H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00403
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0555; 0558

51
[ 1220220-21-2 ]
1-(5-bromo-2-methylpyridin-3-yl)tetrahydropyrimidin-2(1H)-one [ No CAS ]
N-[6-methyl-5-(2-oxotetrahydropyrimidin-1(2H)-yl)-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 0.333333h;Microwave irradiation; Inert atmosphere;	[00407] To a mixture of 1-(5-bromo-2-methylpyridin-3-yl)tetrahydropyrimidin-2(1I1)-one (0.178 g, 0.658 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.207 g, 0.789 mmol) and tetrakis(triphenylphosphine)palladium(0) (22.79 mg, 0.01972 mmol) in EtOH (5.0 niL) and toluene (5.0 mL) under argon was added sodium carbonate (1.0 M in Water, 0.85 mL, 0.85 mmol). The mixture was subjected to microwave irradiation at 120C for 20 mm. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography and then by HPLC to give N-[6- methyl-5-(2-oxotetrahydropyrimidin-1(211)-yl)-3,4?-bipyridin-2?-yl]acetamide 1-460 as a white solid (115mg, 54%). LCMS (FA): mz 326.4 (M+H). in NMR (400 MFIz, DMSO-d6) 6 10.63(s, in), 867(s, in), 8.37(m, 2n), 7.93(s, in), 7.45 (s, in), 6.71 (s, in), 3.66 (bs, in), 3.27 (m, 2n2.46 (m, 4n), 2.05(m, 2F1).
54%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	Step 3: N-[6-methyl-5-(2-oxotetrahydropyrimidin-1 (2H)-yl)-3,4'-bipyridin-2'-yl]acetamide To a mixture of 1-(5-bromo-2-methylpyridin-3-yl)tetrahydropyrimidin-2(1H)-one (0.178 g, 0.658 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.207 g, 0.789 mmol) and tetrakis(triphenylphosphine)palladium(0) (22.79 mg, 0.01972 mmol) in EtOH (5.0 mL) and toluene (5.0 mL) under argon was added sodium carbonate (1.0 M in Water, 0.85 mL, 0.85 mmol). The mixture was subjected to microwave irradiation at 120 C. for 20 min. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography and then by HPLC to give N-[6-methyl-5-(2-oxotetrahydropyrimidin-1 (2H)-yl)-3,4'-bipyridin-2'-yl]acetamide I-460 as a white solid (115 mg, 54%). LCMS (FA): m/z=326.4 (M+H). 1H NMR (400 MHz, DMSO-d6) delta 10.63 (s, 1H), 867(s, 1H), 8.37 (m, 2H), 7.93 (s, 1H), 7.45 (s, 1H), 6.71 (s, 1H), 3.66 (bs, 1H), 3.27 (m, 2H2.46 (m, 4H), 2.05 (m, 2H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00407
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0560; 0563

52
[ 1220220-21-2 ]
1-(2-amino-5-bromopyridin-3-yl)pyrrolidin-2-one [ No CAS ]
N-[6-amino-5-(2-oxopyrrolidin-1-yl)-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39.4%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 0.25h;Microwave irradiation; Inert atmosphere; Sealed tube;	[00409] A mixture of 1-(2-ammno-5-bromopyridin-3-yl)pyrrolidin-2-one (0.0380 g, 0.148 mmol), N[4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (0.05 06 g, 0.193 mmol) and tetrakis(triphenylphosphine)palladium(0) (5.14 mg, 0.00445 mmol) in toluene (1.3 mL) and EtOH (0.7 niL) was placed in a microwave vial. The vial was sealed, flushed with argon, and sodium carbonate (1.00 M in water, 0.178 mL, 0.178 mmol) was added. The mixture was subjected to microwave irradiation at 120 C for 15 mm. The mixture was concentrated and the crude product was purified by HPLC to give N-[6-amino-5-(2-oxopyrrolidin-1-yl)-3,4?-bipyridin-2?-yl]acetamide I-337as a white powder (18.2mg, 39.4%). LCMS (FA): m/z= 312.2 (M+H). ?H NMR (400 MHz, DMSO-d6) 6 10.58(s,in), 8.60(br, in), 8.42(m, 2H), 8.37(d, J=5.2, in), 8.15 (d, 1FI), 7.49 (d, J=5.2, 1FI), 4.66 (br, 1FI), 3.30 (m, 21-I), 2.90 (m, 21-I), i.95 (m, 2H)
39.4%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 0.25h;Microwave irradiation; Inert atmosphere;	Step 3: N-[6-amino-5-(2-oxopyrrolidin-1-yl)-3,4'-bipyridin-2'-yl]acetamide A mixture of 1-(2-amino-5-bromopyridin-3-yl)pyrrolidin-2-one (0.0380 g, 0.148 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.0506 g, 0.193 mmol) and tetrakis(triphenylphosphine)palladium(0) (5.14 mg, 0.00445 mmol) in toluene (1.3 mL) and EtOH (0.7 mL) was placed in a microwave vial. The vial was sealed, flushed with argon, and sodium carbonate (1.00 M in water, 0.178 mL, 0.178 mmol) was added. The mixture was subjected to microwave irradiation at 120 C. for 15 min. The mixture was concentrated and the crude product was purified by HPLC to give N-[6-amino-5-(2-oxopyrrolidin-1-yl)-3,4'-bipyridin-2'-yl]acetamide I-337 as a white powder (18.2 mg, 39.4%). LCMS (FA): m/z=312.2 (M+H). 1H NMR (400 MHz, DMSO-d6) delta 10.58 (s, 1H), 8.60 (br, 1H), 8.42 (m, 2H), 8.37(d, J=5.2, 1H), 8.15 (d, 1H), 7.49 (d, J=5.2, 1H), 4.66 (br, 1H), 3.30 (m, 2H), 2.90 (m, 2H), 1.95 (m, 2H)

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00409
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0564; 0566

53
[ 1220220-21-2 ]
N-(5-bromopyridin-3-yl)-2,4-difluorobenzamide [ No CAS ]
N-(2’-acetamido-3,4’-bipyridin-5-yl)-2,4-difluorobenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; toluene;Microwave irradiation;	[00288] To a reaction vial were added<strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.142 g, 0.544 mmol)), N-(5-bromopyridin-3-yl)benzamide (0.196 g, 0.707 mmol), potassium carbonate (150 mg, 1.09 mmol) and dioxane-water(6:1 mixture of 1,4-dioxane:water; 4.80 niL). The mixture was flushed with argon and Pd(dppf)C12 (22.4 mg, 0.027 mmol) was added. The reaction was sealed and heated at 120C in an oil bath for 18 h. The reaction was filtered through celite and the celite was washed with DCM. The filtrate was concentrated and the residue was purified by column chromatography to yield N-(2?-acetamido-3,4?-bipyridin-5-yl)benzamide (60 mg, 33.3%).Step 2 conditions use Pd(PPh3)4, 1.0 M Na2CO3 toluene, and EtOH under microwave irradiation

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00288; 00289

54
[ 1220220-21-2 ]
N-(5-bromopyridin-3-yl)-2,4-difluoro-N-methylbenzamide [ No CAS ]
N-(2’-acetamido-3,4’-bipyridin-5-yl)-2,4-difluoro-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 120℃; for 0.333333h;Microwave irradiation; Inert atmosphere;	[00419] A vial containing N-(5-bromopyridin-3-yl)-2,4-difluoro-N-methylbenzamide (0.200 g, 0.611 mmol), EtOH (4 mL), toluene (4 mL), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.208 g, 0.795 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.02 12 g, 0.0183 mmol) was evacuated and backfilled with argon. Sodium carbonate (1.0 M in Water, 0.734 mL, 0.734 mmol) was added. The mixture was subjected to microwave irradiation at 120 C for 20mm. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2504, filtered and concentrated. The crude compound was purified by column chromatography as a brown oil 1-397 (0.238 g, 100%). LCMS (FA): m/z 383.3(M+H). ?H NMR (400MHz, CDC13) 6 8.72 (s, in), 8.46- 8.31 (m, 3H), 7.74 (br s, in), 7.50(q, J=7.7 Hz, in), 7.29 (s, in), 7.20-7.09 (m, in), 6.92 (br t, J=7.5 Hz, in), 6.64 (br s, in), 3.56 (s, 3H), 3.51 (d, J=4.3 Hz, in), 2.27 (s, 3H)
100%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; at 120℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	Step 3: N-(2?-acetamido-3,4?-bipyridin-5-yl)-2,4-difluoro-N-methylbenzamide (0579) A vial containing N-(5-bromopyridin-3-yl)-2,4-difluoro-N-methylbenzamide (0.200 g, 0.611 mmol), EtOH (4 mL), toluene (4 mL), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.208 g, 0.795 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.0212 g, 0.0183 mmol) was evacuated and backfilled with argon. Sodium carbonate (1.0 M in Water, 0.734 mL, 0.734 mmol) was added. The mixture was subjected to microwave irradiation at 120 C. for 20 min. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The crude compound was purified by column chromatography as a brown oil I-397 (0.238 g, 100%). LCMS (FA): m/z=383.3(M+H). 1H NMR (400 MHz, CDCl3) 6=8.72 (s, 1H), 8.46-8.31 (m, 3H), 7.74 (br s, 1H), 7.50 (q, J=7.7 Hz, 1H), 7.29 (s, 1H), 7.20-7.09 (m, 1H), 6.92 (br t, J=7.5 Hz, 1H), 6.64 (br s, 1H), 3.56 (s, 3H), 3.51 (d, J=4.3 Hz, 1H), 2.27 (s, 3H)

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00419
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0576; 0579

55
[ 1220220-21-2 ]
C₁₄H₁₁BrF₂N₂O [ No CAS ]
N-(2’-acetamido-6-methyl-3,4’-bipyridin-5-yl)-2,4-difluoro-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; caesium carbonate; In N,N-dimethyl-formamide; at 110℃;Microwave irradiation;	[00419] A vial containing N-(5-bromopyridin-3-yl)-2,4-difluoro-N-methylbenzamide (0.200 g, 0.611 mmol), EtOH (4 mL), toluene (4 mL), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.208 g, 0.795 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.02 12 g, 0.0183 mmol) was evacuated and backfilled with argon. Sodium carbonate (1.0 M in Water, 0.734 mL, 0.734 mmol) was added. The mixture was subjected to microwave irradiation at 120 C for 20mm. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2504, filtered and concentrated. The crude compound was purified by column chromatography as a brown oil 1-397 (0.238 g, 100%).Step 2: Cs2CO3 DMF, 110C, microwave irradiation

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00419; 00420
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0576; 0579

56
[ 914358-73-9 ]
[ 1220220-21-2 ]
N-(5-amino-6-methyl-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; for 2.5h;Reflux;	[00248] A mixture of N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin- 2-yl]acetamide (4.20 g, 16.0 mmol), 5-bromo-2-methylpyridin-3-amine (2.00 g, 10.7 mmol), cesium carbonate (10.4 g, 32.1 mmol), Pd(dppf)C12 (0.88 g, 1.1 mmol) in 1,4-dioxane (36.0 mL) and water (6.0 niL) was heated to reflux for 2.5 h. After cooling toil, water was added and the mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated by rotary evaporation. The crude compound was purified by column chromatography to provide N-(5-amino-6-methyl-3,4?-bipyridin-2?-yl)acetamide (0.94 g, 36%). LCMS (FA): m/z 243.1 (M+H).
36%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; for 2.5h;Reflux;	Step 1: N-(5-amino-6-methyl-3,4'-bipyridin-2'-yl)acetamide A mixture of <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (4.20 g, 16.0 mmol), 5-bromo-2-methylpyridin-3-amine (2.00 g, 10.7 mmol), cesium carbonate (10.4 g, 32.1 mmol), Pd(dppf)Cl2 (0.88 g, 1.1 mmol) in 1,4-dioxane (36.0 mL) and water (6.0 mL) was heated to reflux for 2.5 h. After cooling to rt, water was added and the mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated by rotary evaporation. The crude compound was purified by column chromatography to provide N-(5-amino-6-methyl-3,4'-bipyridin-2'-yl)acetamide (0.94 g, 36%). LCMS (FA): m/z=243.1 (M+H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00248
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0341-0342

57
[ 1083326-22-0 ]
[ 1220220-21-2 ]
N-(5-[(2,4-difluorophenyl)sulfonyl]amino}-6-methyl-3,4'-bipyridin-2'-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 18h;Inert atmosphere;	[00228] N-(5-bromopyridin-3-yl)-3-chloropropane-i-sulfonamide (0.29 g, 0.79 mmol), N-[4-(4,4,5,5- tetramethyl-i,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (0.27 g, 1.03 mmol), [1,1?- bis(diphenylphosphino)ferrocene]dichloropalladium (65 mg, 0.079 mmol) and cesium carbonate (0.77 g, 2.37 mmol) were taken up in 1,4-dioxane (2.16 mL) and water (0.37 mL) under an atmosphere of nitrogen. The reaction mixture was heated at 110C for 18 h. The reaction mixture was cooled toil and water was added and extracted with EtOAc. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated by rotary evaporation. The crude compound was purified by column chromatography to provide N-(5-[(2,4-difluorophenyl)sulfonyl]amino}-6-methyl-3,4?-bipyridin- 2?-yl)acetamide (142 mg, 43%). LCMS (FA): m/z 419.3 (M+H). ?H NMR (500 MFIz, DMSO-d6) 610.65 (s, 1H), 10.60 (s, 1H), 8.67 (d, J= 2.11 Hz, 1H), 8.39 (d, J= 5.17 Hz, 1H), 8.28 (s, 1H), 7.83 (m, 1H), 7.73 (d, J= 2.14 Hz, 1H), 7.59 (ddd,J= 2.50, 9.06, 11.20 Hz, 1H), 7.38 (dd, J= 1.67, 5.28 Hz, 1H),7.24 (m, 1H), 2.36 (s, 3H), 2.14 (s, 3H).
43%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 18h;Inert atmosphere;	Step 2: N-(5-[(2,4-difluorophenyl)sulfonyl]amino}-6-methyl-3,4'-bipyridin-2'-yl)acetamide N-(5-bromopyridin-3-yl)-3-chloropropane-1-sulfonamide (0.29 g, 0.79 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (0.27 g, 1.03 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (65 mg, 0.079 mmol) and cesium carbonate (0.77 g, 2.37 mmol) were taken up in 1,4-dioxane (2.16 mL) and water (0.37 mL) under an atmosphere of nitrogen. The reaction mixture was heated at 110 C. for 18 h. The reaction mixture was cooled to rt and water was added and extracted with EtOAc. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated by rotary evaporation. The crude compound was purified by column chromatography to provide N-(5-[(2,4-difluorophenyl)sulfonyl]amino}-6-methyl-3,4'-bipyridin-2'-yl)acetamide (142 mg, 43%). LCMS (FA): m/z=419.3 (M+H). 1H NMR (500 MHz, DMSO-d6) delta 10.65 (s, 1H), 10.60 (s, 1H), 8.67 (d, J=2.11 Hz, 1H), 8.39 (d, J=5.17 Hz, 1H), 8.28 (s, 1H), 7.83 (m, 1H), 7.73 (d, J=2.14 Hz, 1H), 7.59 (ddd, J=2.50, 9.06, 11.20 Hz, 1H), 7.38 (dd, J=1.67, 5.28 Hz, 1H), 7.24 (m, 1H), 2.36 (s, 3H), 2.14 (s, 3H).

Reference： [1]Patent: WO2015/108861,2015,A1 .Location in patent: Paragraph 00228
[2]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0306; 0308

58
[ 1220220-21-2 ]
5-bromo-3-(2,4-difluorophenylsulfonamido)-2-methylpyridine 1-oxide [ No CAS ]
N-[4-(5-[(2,4-difluorophenyl)sulfonyl]amino}-6-methyl-1-oxidopyridin-3-yl)pyridin-2-yl]acetamide [ No CAS ]

Reference： [1]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0306; 0308-0309

59
[ 1220220-21-2 ]
5-bromo-N,N-dimethyl-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide [ No CAS ]
N-{4-[3-(dimethylsulfamoyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridin-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere;	Step 3: N-{4-[13-(dimethylsulfamoyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridin-2-yl}acetamide Followed the procedure in Step 2 of Example 23 with the following modification: Heated at 100 C. for 2 h. LCMS (AA): m/z=360.1 (M+H).

Reference： [1]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0418; 0421

60
[ 1220220-21-2 ]
7-bromo-2-methyl-3,4-dihydro-2H-pyrido[2,3-e][1,2,4]thiadiazine 1,1-dioxide [ No CAS ]
N-[4-(2-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-e][1,2,4]thiadiazin-7-yl)pyridin-2-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	Step 2: N-[4-(2-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-e][1,2,4]thiadiazin-7-yl)pyridin-2-yl]acetamide Followed the procedure in Step 2 of Example 23 to yield N-[4-(2-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-e][1,2,4]thiadiazin-7-yl)pyridin-2-yl]acetamide (20 mg, 54%). LCMS (AA): m/z=334.4 (M+H).

Reference： [1]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0423; 0425

61
[ 1220220-21-2 ]
6-bromo-1-(cyclopropylmethyl)-1H-imidazo[4,5-b]pyridine [ No CAS ]
N-{4-[1-(cyclopropylmethyl)-1H-imidazo[4,5-b]pyridin-6-yl]pyridin-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 5h;Inert atmosphere;	Step 2: N-{4-[1-(cyclopropylmethyl)-1H-imidazo[4,5-b]pyridin-6-yl]pyridin-2-yl}acetamide Followed the procedure in Step 2 of Example 23 with the following modification: Heated at 120 C. for 5 h to yield N-{4-[1-(cyclopropylmethyl)-1H-imidazo[4,5-b]pyridin-6-yl]pyridin-2-yl}acetamide (62 mg, 83%). LCMS (AA): m/z=308.4 (M+H).

Reference： [1]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0426; 0428

62
[ 1220220-21-2 ]
6-bromo-2-methyl-3H-imidazo[4,5-b]pyridine [ No CAS ]
N-[4-(2-methyl-3H-imidazo[4,5-b]pyridin-6-yl)pyridin-2-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 15h;Inert atmosphere;	Step 2: N-[4-(2-methyl-3H-imidazo[4,5-b]pyridin-6-yl)pyridin-2-yl]acetamide Followed the procedure in Step 2 of Example 23 with the following modification: Heated at 120 C. for 15 h to yield N-[4-(2-methyl-3H-imidazo[4,5-b]pyridin-6-yl)pyridin-2-yl]acetamide (13 mg, 14%). LCMS (AA): m/z=268.1 (M+H).

Reference： [1]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0429; 0431

63
[ 1220220-21-2 ]
N-(bicyclo[1.1.1]pent-1-yl)-5-chloro-2-methylpyridine-3-sulfonamide [ No CAS ]
N-[5-(bicyclo[1.1.1]pent-1-ylsulfamoyl)-6-methyl-3,4’-bipyridin-2’-yl]acetamide [ No CAS ]
N-(6-methyl-5-sulfamoyl-3,4’-bipyridin-2’-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%; 26%	With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; XPhos; In 1,4-dioxane; water; at 110℃; for 1.5h;Sealed tube; Inert atmosphere;	Step 4: N-[5-(bicyclo[1.1.1]pent-1-ylsulfamoyl)-6-methyl-3,4'-bipyridin-2'-yl]acetamide (I-418) and N-(6-methyl-5-sulfamoyl-3,4'-bipyridin-2'-yl)acetamide (I-395) A microwave tube was charged with N-(bicyclo[1.1.1]pent-1-yl)-5-chloro-2-methylpyridine-3-sulfonamide (83 mg, 0.30 mmol), <strong>[1220220-21-2]N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide</strong> (98.6 mg, 0.376 mmol), 2-dicyclohexylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl (14 mg, 0.029 mmol), tris(dba)dipalladium(0) (8.3 mg, 0.0092 mmol) and potassium acetate (89 mg, 0.91 mmol). The tube was purged with nitrogen and 1,4-dioxane (2.4 mL) was added. The reaction mixture was allowed to stir for 2 min and water (0.51 mL) was added. The tube was purged with nitrogen three times, sealed, and was heated at 110 C. in oil bath for 1.5 h. After the reaction mixture was allowed to cool to rt, the mixture was diluted with EtOAc (25 ml) and water (15 ml). The aqueous solution was separated and further extracted with EtOAc (15 ml). The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The products were purified by column chromatography using 0-3% MeOH/DCM over 25 min. to give N-[5-(bicyclo[1.1.1]pent-1-ylsulfamoyl)-6-methyl-3,4'-bipyridin-2'-yl]acetamide (I-418) (25 mg, 22%) as a white solid. LCMS (FA): m/z=373.4 (M+H). 1H NMR (400 MHz, DMSO-d6) delta 10.68 (s, 1H), 9.12 (s, 1H), 9.05 (d, J=2.2 Hz, 1H), 8.44-8.47 (m, 2H), 8.39 (d, J=2.2 Hz, 1H), 7.51-7.55 (m, 1H), 2.83 (s, 3H), 2.31 (s, 1H), 2.14 (s, 3H), 1.77 (s, 6H). Further elution using 6% MeOH/DCM gave by product N-(6-methyl-5-sulfamoyl-3,4?-bipyridin-2?-yl)acetamide (I-395) (24 mg, 26%) as a white solid. LCMS (FA): m/z=307.4 (M+H). 1H NMR (400 MHz, DMSO-d6) delta 10.68 (s, 1H), 8.99 (d, J=2.2 Hz, 1H), 8.44-8.47 (m, 1H), 8.43-8.39 (m, 2H), 7.76 (s, 2H), 7.48-7.52 (m, 1H), 2.85 (s, 3H), 2.14 (s, 3H).

Reference： [1]Patent: US2015/225422,2015,A1 .Location in patent: Paragraph 0542; 0546

64
[ 1220220-21-2 ]
N-{5-[(butylsulfonyl)amino]-6-methyl-3,4’-bipyridin-2’-yl}acetamide [ No CAS ]

Reference： [1]Patent: US2015/225422,2015,A1

65
[ 1220220-21-2 ]
(S)-tert-butyl (1-(4-bromo-2-methylphenoxy)-4-methylpentan-2-yl)carbamate [ No CAS ]
(S)-tert-butyl (1-(4-(2-acetamidopyridin-4-yl)-2-methylphenoxy)-4-methylpentan-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 80℃;Inert atmosphere;	A mixture of sodium carbonate (0.061 mL, 0.121 mmol), <strong>[1220220-21-2]N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide</strong> (0.028 g, 0.105 mmol), (S)-tert-butyl (1-(4-bromo-2-methylphenoxy)-4-methylpentan-2-yl)carbamate (0.0312 g, 0.081 mmol) in dioxane (1 mL) was purged with nitrogen 5 times. PdCl2(dppf) (5.91 mg, 8.08 muiotaetaomicron) was added to the reaction mixture and the reaction was heated at 80 C overnight. The reaction was cooled to room temperature and diluted with ethyl acetate. The organic layer was separated and washed with brine (IX). The ethyl acetate layer was separated, dried (Na2SO4), filtered and concentrated under reduced pressure . The crude was used as it is at the next reaction. LCMS (ESI) m/e 442.3 [(M+H)+, calcd C25H36N3O4, 442.3]; LC/MS retention time (method B): = 2.13 min.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 80℃;Inert atmosphere;	A mixture of sodium carbonate (0.061 mL, 0.121 mmol), N-(4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (0.028 g, 0.105 mmol), (S)-tert-bu y (l-(4-bromo-2-methylphenoxy)-4-methylpentan-2-yl)carbamate (0.0312 g, 0.081 mmol) in dioxane (1 mL) was purged with nitrogen 5 times. PdCl2(dppf) (5.91 mg, 8.08 muiotatauiotaomicron) was added to the reaction mixture and the reaction was heated at 80 C overnight. The reaction was cooled to room temperature and diluted with ethyl acetate. The organic layer was separated and washed with brine (IX). The ethyl acetate layer was separated, dried Na2S04), filtered and concentrated under reduced pressure . The crude was used as it is at the next reaction. LCMS (ESI) m/e 442.3 [(M+H)+, calcd C25H36N3O4, 442.3]; LC/MS retention time (method B): /R = 2.13 min.

Reference： [1]Patent: WO2015/153720,2015,A1 .Location in patent: Page/Page column 33
[2]Patent: WO2017/59085,2017,A1 .Location in patent: Page/Page column 32; 33

66
[ 1220220-21-2 ]
(S)-tert-butyl (1-(4-bromo-2-chlorophenoxy)-4-methylpentan-2-yl)carbamate [ No CAS ]
(S)-tert-butyl (1-(4-(2-acetamidopyridin-4-yl)-2-chlorophenoxy)-4-methylpentan-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 80℃;Inert atmosphere;	The mixture of sodium carbonate (0.113 mL, 0.226 mmol), N-(4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (0.051 g, 0.196 mmol), (S)-tert-buty (l-(4-bromo-2-chlorophenoxy)-4-methylpentan-2-yl)carbamate (0.0612 g, 0.150 mmol) in dioxane (1 mL) was evacuated and back-filled with Nu2 (5X). PdCl2(dppf) (0.011 g, 0.015 mmol) was added to the reaction mixture and the reaction was heated at 80 C overnight. The reaction was diluted with ethyl acetate and washed with brine (IX). The ethyl acetate layer was separated, dried Na2S04), filtered and concentrated under reduced pressure . The crude was purified by silica gel chromatography (50% ethyl acetate in hexanes) to afford. (S)-tert-buty (l-(4-(2- acetamidopy ridin-4-y l)-2-chlorophenoxy )-4-methy lpentan-2-y l)carbamate (51.7mg, 0.112 mmol, 74% yield). LCMS (ESI) m/e 462.2 [(M+H)+, calcd C24H33CIN3O4, 462.2]; LC/MS retention time (method B): fa = 2.21 min.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 80℃;Inert atmosphere;	The mixture of sodium carbonate (0.113 mL, 0.226 mmol), <strong>[1220220-21-2]N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide</strong> (0.051 g, 0.196 mmol), (iS)-tert-butyl (1-(4-bromo-2-chlorophenoxy)-4-methylpentan-2-yl)carbamate (0.0612 g, 0.150 mmol) in dioxane (1 mL) was evacuated and back-filled with N2 (5X). PdCl2(dppf) (0.011 g, 0.015 mmol) was added to the reaction mixture and the reaction was heated at 80 C overnight. The reaction was diluted with ethyl acetate and washed with brine (IX). The ethyl acetate layer was separated, dried (Na2SO4), filtered and concentrated under reduced pressure . The crude was purified by silica gel chromatography (50% ethyl acetate in hexanes) to afford. (S)-tert-butyl (1-(4-(2-acetamidopyridin-4-yl)-2-chlorophenoxy)-4-methylpentan-2-yl)carbamate (51.7mg, 0.112 mmol, 74% yield). LCMS (ESI) m/e 462.2 [(M+H)+, calcd C24H33ClN3O4, 462.2]; LC/MS retention time (method B): tR = 2.21 min.

Reference： [1]Patent: WO2017/59085,2017,A1 .Location in patent: Page/Page column 34; 35
[2]Patent: WO2015/153720,2015,A1 .Location in patent: Page/Page column 34; 35

67
[ 1220220-21-2 ]
(S)-tert-butyl (1-(4-bromo-2-chlorophenoxy)-4-methylpentan-2-yl)carbamate [ No CAS ]
(S)-N-(4-(4-((2-amino-4-methylpentyl)oxy)-3-chlorophenyl)pyridin-2-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2015/153720,2015,A1
[2]Patent: WO2017/59085,2017,A1

68
[ 1220220-21-2 ]
(S)-1-(4-bromo-2-(trifluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine [ No CAS ]
(S)-N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3-(trifluoromethyl)phenyl)pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; toluene; at 130℃; for 2h;Inert atmosphere; Microwave irradiation;	To a 2 mL vial was added (5)-1-(4-bromo-2-(trifluoromethyl)phenoxy)-2,4- dimethylpentan-2-amine (43.5 mg, 0.123 mmol), N-(4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridin-2-yl)acetamide (26.5 mg, 0.147 mmol) (prepared as described in Example 1 , Part A), and Na2CO3 (0.184 mL, 0.368 mmol) in dioxane (0.5 mL) under nitrogen to give a colorless suspension. 1,1'- bis(diphenylphosphino)ferrocene palladium(II) dichloride, toluene (5.05 mg, 6.14 mumomicronl) was added under nitrogen. The vial was sealed and heated at 130 C (microwave) for 2 h (100 C oil heating for 2 h was fine and was used for all other examples). The mixture was cooled to rt and diluted with EtOAc then passed through a plug of Na2SO4. The organic solution was concentrated under reduced pressure . The residue was purified by reverse phase HPLC (acetonitrile: water with 10 mM ammonium) to give (5)-N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3- (trifluoromethyl)phenyl)pyridin-2-yl)acetamide (24 mg, 0.057 mmol, 47% yield) as an off-white solid. 1H NMR (500 MHz, DMSO-d6) delta 10.58 (s, 1H), 8.36 (d, J = 5.2 Hz, 2H), 7.97 (t, J = 8.1 Hz, 1H), 7.89 (s, 1H), 7.44 (d, J = 5.4 Hz, 1H), 7.38 (d, J = 8.7 Hz, 1H), 3.86 (q, J = 8.8 Hz, 2H), 2.13 (s, 3H), 1.79 (dq, J = 10.2, 5.2, 4.0 Hz, 1H), 1.39 (d, J = 5.5 Hz, 2H), 1.12 (s, 3H), 0.91 (d, J = 6.6 Hz, 6H); LCMS (ESI) m/e 410.2 [(M-H)", calcd C20H23F3N3O2, 410.2]; LC/MS retention time (method B): tR = 1.87 min.
24 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; toluene; at 100 - 130℃; for 4h;Inert atmosphere; Sealed tube; Microwave irradiation;	To a 2 mL vial was added (5)-l-(4-bromo-2-(trifluoromethyl)phenoxy)-2,4- dimethylpentan-2-amine (43.5 mg, 0.123 mmol), N-(4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)pyridin-2-yl)acetamide (26.5 mg, 0.147 mmol) (prepared as described in Example 1, Part A), and Na2C03 (0.184 mL, 0.368 mmol) in dioxane (0.5 mL) under nitrogen to give a colorless suspension. 1,1'- bis(diphenylphosphino)ferrocene palladium(II) dichloride, toluene (5.05 mg, 6.14 muiotaetaomicron) was added under nitrogen. The vial was sealed and heated at 130 C (microwave) for 2 h (100 C oil heating for 2 h was fine and was used for all other Examples). The mixture was cooled to rt and diluted with EtOAc then passed through a plug of Na2S04. The organic solution was concentrated under reduced pressure. The residue was purified by reverse phase HPLC (acetonitrile: water with 10 mM ammonium) to give (5 -N-(4-(4-((2-amino-2,4-dimethylpentyl)oxy)-3- (trifluoromethyl)phenyl)pyridin-2-yl)acetamide (24 mg, 0.057 mmol, 47% yield) as an off-white solid. NMR (500 MHz, DMSO-de) delta 10.58 (s, 1H), 8.36 (d, J = 5.2 Hz, 2H), 7.97 (t, J = 8.1 Hz, 1H), 7.89 (s, 1H), 7.44 (d, J = 5.4 Hz, 1H), 7.38 (d, J = 8.7 Hz, 1H), 3.86 (q, J = 8.8 Hz, 2H), 2.13 (s, 3H), 1.79 (dq, J = 10.2, 5.2, 4.0 Hz, 1H), 1.39 (d, J = 5.5 Hz, 2H), 1.12 (s, 3H), 0.91 (d, J = 6.6 Hz, 6H); LCMS (ESI) m/e 410.2 [(M-H) calcd C20H23F3N3O2, 410.2]; LC/MS retention time (method B): /R = 1.87 min.

Reference： [1]Patent: WO2015/153720,2015,A1 .Location in patent: Page/Page column 52
[2]Patent: WO2017/59085,2017,A1 .Location in patent: Page/Page column 51; 52

69
[ 1220220-21-2 ]
(S)-tert-butyl (1-(4-bromo-2-fluorophenoxy)-4-methylpentan-2-yl)carbamate [ No CAS ]
(S)-tert-butyl (1-(4-(2-acetamidopyridin-4-yl)-2-fluorophenoxy)-4-methylpentan-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; toluene; at 130℃; for 2h;Inert atmosphere; Microwave irradiation;	To a 15 mL vial was added <strong>[1220220-21-2]N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide</strong> (208 mg, 0.792 mmol), {S)-tert-tert (1-(4-bromo-2- fluorophenoxy)-4-methylpentan-2-yl)carbamate (258 mg, 0.66 mmol), and Na2CO3 (0.990 mL, 1.980 mmol) in dioxane (2 mL) under nitrogen to give a colorless suspension. 1,1'-Bis(diphenylphosphino)ferrocenepalladium(II) dichloride, toluene (27.1 mg, 0.033 mmol) was added under nitrogen. The vial was sealed and heated at 130 C (microwave) for 2 h. The mixture was diluted with water and EtOAc. The layers were separated. The organic layer was washed with brine, dried (Na2S04) and concentrated. The residue was purified by silica gel column chromatography (up to 70% EtOAc/hexane) to afford the desired product (200 mg, 0.449 mmol, 68% yield for two steps) as a colorless oil: 1H NMR (400 MHz, Chloroform-d) delta 8.79 (s, 1H), 8.46 (s, 1H), 8.29 (d, J = 5.4 Hz, 1H), 7.50 - 7.38 (m, 2H), 7.21 (dd, J = 5.2, 1.7 Hz, 1H), 7.06 (t, J = 8.7 Hz, 1H), 4.81 (d, J = 9.2 Hz, 1H), 4.12 - 3.96 (m, 3H), 2.25 (s, 3H), 1.74 (dq, J = 13.5, 6.5, 6.1 Hz, 1H), 1.63 - 1.52 (m, 2H), 1.47 (s, 9H), 0.98 (dd, J = 6.6, 3.3 Hz, 6H); LCMS (ESI) m/e 446.2 [(M+H)+, calcd C24H33F1N3O4, 446.2]; LC/MS retention time (method B): tR = 2.11 min.
68%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; toluene; at 130℃; for 2h;Inert atmosphere; Sealed tube; Microwave irradiation;	To a 15 mL vial was added N-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)pyridin-2-yl)acetamide (208 mg, 0.792 mmol), (S)-ter /-butyl (l-(4-bromo-2- fluorophenoxy)-4-methylpentan-2-yl)carbamate (258 mg, 0.66 mmol), and Na2C03 (0.990 mL, 1.980 mmol) in dioxane (2 mL) under nitrogen to give a colorless suspension. l,l'-Bis(diphenylphosphino)ferrocenepalladium(II) di chloride, toluene (27.1 mg, 0.033 mmol) was added under nitrogen. The vial was sealed and heated at 130 C (microwave) for 2 h. The mixture was diluted with water and EtO Ac. The layers were separated. The organic layer was washed with brine, dried (Na2S04) and concentrated. The residue was purified by silica gel column chromatography (up to 70% EtOAc/hexane) to afford the desired product (200 mg, 0.449 mmol, 68% yield for two steps) as a colorless oil: NMR (400 MHz, Chloroform-d) delta 8.79 (s, 1H), 8.46 (s, 1H), 8.29 (d, J = 5.4 Hz, 1H), 7.50 - 7.38 (m, 2H), 7.21 (dd, J = 5.2, 1.7 Hz, 1H), 7.06 (t, J = 8.7 Hz, 1H), 4.81 (d, J = 9.2 Hz, 1H), 4.12 - 3.96 (m, 3H), 2.25 (s, 3H), 1.74 (dq, J = 13.5, 6.5, 6.1 Hz, 1H), 1.63 - 1.52 (m, 2H), 1.47 (s, 9H), 0.98 (dd, J = 6.6, 3.3 Hz, 6H); LCMS (ESI) m/e 446.2 [(M+H)+, calcd C24H33F1N3O4, 446.2]; LC/MS retention time (method B): /R = 2.11 min.

Reference： [1]Patent: WO2015/153720,2015,A1 .Location in patent: Page/Page column 24
[2]Patent: WO2017/59085,2017,A1 .Location in patent: Page/Page column 23; 24

70
[ 1220220-21-2 ]
[ 460081-18-9 ]
ethyl 2-(2-acetamidopyridin-4-yl)oxazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 4h;Inert atmosphere;	Step 1: Preparation of ethyl 2-(2-acetamidopyridin-4-yl)oxazole-4-carboxylate To a solution of N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (2.78g, 10.04mmol) in 1,2-dimethoxyethane (30ml) under nitrogen was added ethyl 2-chlorooxazole-4-carboxylate (1g, 7.09mmol), sodium carbonate (106mg, 21.2mmol) in water (5ml) and Pd(DPPF)Cl2 (259mg, 0.354mmol) and heated to 90C for 4h to get the crude compound which was purifiedby 60-120 silica gel column chromatography using 50% ethyl acetate in hexane as eluent to obtain the title compound (680mg, 36%). LCMS: 276.3 (M+1)+.

Reference： [1]Patent: WO2015/193846,A1 .Location in patent: Page/Page column 41
Patent: ,2015, .Location in patent: Page/Page column 41

71
[ 1220220-21-2 ]
2-(2-aminopyridin-4-yl)oxazole-4-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2015/193846,A1
Patent: ,2015,

72
[ 1220220-21-2 ]
2-(2-acetamidopyridin-4-yl)oxazole-4-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2015/193846,A1
Patent: ,2015,

73
[ 1220220-21-2 ]
5-bromo-4-(4-fluorophenyl)-2-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole [ No CAS ]
N-(4-(4-(4-fluorophenyl)-2-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyridin-2-yl)acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5613 - 5637
[2]Angewandte Chemie - International Edition,2016,vol. 55,p. 10890 - 10894
Angew. Chem.,2016,vol. 128,p. 11050 - 11054,5

74
[ 1220220-21-2 ]
4-(4-(4-fluorophenyl)-2-(methylthio)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyridine-2-amine [ No CAS ]