[ CAS No. 1220220-21-2 ]

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 1~68

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 ]