Name: 1020174-04-2|1-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole|97%
Brand: Ambeed
SKU: A117827
Rating: 94 (26 reviews)

1
(4-(7-bromo-5-chloro-8-methoxy-quinazolin-2-ylamino)phenyl)(morpholin-4-yl)methanone [ No CAS ]
[ 1020174-04-2 ]
(4-(5-chloro-8-methoxy-7-(1-methyl-1H-pyrazol-4-yl)-quinazolin-2-ylamino)phenyl)morpholin-4-yl-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; at 120℃; for 0.166667h;Microwave irradiation;	Step 4. Preparation pf N-(5-chloro-8-methoxy-7-(l-methyl-lH-pyrazol-4-yl)quinazolin-2- yl)morpholine-4-carboxatnideTo (4-(7-bromo-5-chloro-8-methoxyquinazolin-2-ylamino)phenyl) (morpholino)methanone (leq) in DME and 2M sodium carbonate solution was added l-methyl-3-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)-lH-pyrazole (3eq) and Pd^pPf)2Cl2-CH2Cl2 (0.05eq) and the mixture was micro waved for 10 min at 12O0C. The reaction mixture was then partitioned between ethyl acetate and water. The organic layer was concentrated and purifedon prep HPLC to yield N-(5- chloro-8-methoxy-7-( 1 -methyl- 1 H-pyrazol-4-yl) quinazolin-2-yl)mophiholine-4-carboxamide. ES/MS m/z 479(MH+).

Reference： [1]Patent: WO2007/117607,2007,A2 .Location in patent: Page/Page column 348

2
[ 1020174-04-2 ]
[ 953039-95-7 ]
7-(1-methyl-1H-pyrazol-4-yl)-N-(4-(morpholine-4-sulfonyl)-phenyl)-quinazolin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; at 120℃; for 0.166667h;Microwave irradiation;	Step 2. Preparation of 7-(l -methyl- lH-pyrazol-4-yl) -N- (4-(motaupholinosulfonyl) phenyl)quinazolin-2-amineTo a solution of 2-(4-(mophiholinosulfonyl)phenylamino) quinazolin-7-yltrifluoromethane sulfonate (leq) in DME was added 2M sodium carbonate solution and l-methyl-4-(4,4,5,5,- tetramethyl-ls3,2-dioxaborolan-2-yl)-lH-pyrazole (3eq) and Pd (dppf)2Cl2.CH2Cl2 (0.05eq) and the mixture was micro waved for 10 min at 1200C. The reaction mixture was then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried, concentrated and purified by semi-preparative HPLC to provide 7-(l -methyl- lH-pyrazol-4-yl) -N- (4- (morpholinosulfonyl) phenyl) quinazolin-2-amine in 60%yield. ES/MS m/z 551.1(MH+).

Reference： [1]Patent: WO2007/117607,2007,A2 .Location in patent: Page/Page column 352

3
[ 1020174-04-2 ]
[ 1041861-97-5 ]
[ 1020173-14-1 ]

Yield	Reaction Conditions	Operation in experiment
56%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 16h;Inert atmosphere;	A solution of Example A23 (3 g, 12.6 mmol), l-methyl-3- (4,4,5, 5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrazole (5.2 g, 25.2 mmol), and Na2C03 (2.7 g, 25.2 mmol) in DME (18 mL) and water (6 mL) was sparged with nitrogen for 20 min. Pd(PPh3)4 (729 mg, 0.63 mmol) was added and the resulting mixture was heated to 100 C for 16 h. The solvent was removed under reduced pressure and the crude product was suspended in water and extracted with EtOAc. The organic layer was washed with brine, dried (Na2SC>4), concentrated in vacuo and purified by silica gel chromatography to give 2-fiuoro-4-(2-(l -methyl- 1 H-pyrazol-4-yl)pyridin-4- yloxy)aniline (2 g, 56% yield). 1H NMR (300 MHz, DMSO-i/6) delta 8.31 (d ,J = 5.7 Hz, 1 H), 8.21 (s, 1 H), 7.92 (s, 1 H), 7.12 (s, J = 2.4 Hz, 1 H), 6.96 (m, 1 H), 6.85-6.72 (m, 2 H), 6.56 (m, 1 H), 5.15 (s, 2 H), 3.84 (s, 3H); MS (ESI) m z: 285.0 (M+H+)
56%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 16.33h;Inert atmosphere;	A solution of 4-(2-chloropyridin-4-yloxy)-2-fluorobenzenamine (3 g, 12.6 mmol), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole</strong> (5.2 g, 25.2 mmol), and Na2CO3 (2.7 g, 25.2 mmol) in DME (18 mL)/water (6 mL) was sparged with nitrogen for 20 min. Pd(PPh3)4 (729 mg, 0.63 mmol) was added and the resulting mixture was heated to 100 C. for 16 h. The solvent was removed under reduced pressure and the crude product was suspended in water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated in vacuo and purified via silica gel chromatography to give 2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (2 g, 56% yield). 1H NMR (300 MHz, DMSO-d6): delta 8.31 (d, J=5.7 Hz, 1H), 8.21 (s, 1H), 7.92 (s, 1H), 7.12 (d, J=2.4 Hz, 1H), 6.96 (m, 1H), 6.85-6.72 (m, 2H), 6.56 (m, 1H), 5.15 (s, 2H), 3.84 (s, 3H); MS (ESI) m/z: 285.0 (M+H+).

Reference： [1]Patent: WO2013/36232,2013,A2 .Location in patent: Paragraph 00259
[2]Patent: US2014/315917,2014,A1 .Location in patent: Paragraph 0514

4
[ 269410-08-4 ]
[ 74-88-4 ]
[ 1020174-04-2 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: l-Methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolcm-2-yl)-lH-pyrazole; N O Potassium tert-butoxide in THF (1.0 M, 0.309 mL, 0.309 mmol) was added to a solution of 3- (4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH-pyrazole (30.0 mg, 0.155 mmol, Alfa Aesar, Cat. No. H27619) in DMF (0.5 mL) and stirred at r.t. for 10 min, and then methyl iodide (28.9 uL, 0.464 mmol) was added and the stirred at r.t. for 1 h. LCMS showed the reaction was complete. The mixture was diluted with ethyl acetate, washed with water and brine, dried over Na2SCu, filtered, and concentrated to give the crude product which was directly used in the next reaction without further purification. LCMS (M+H-82)+: m/z = 127.2.

Reference： [1]Patent: WO2010/75270,2010,A1 .Location in patent: Page/Page column 137

5
[ 1020174-04-2 ]
4-(7-bromo-3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine [ No CAS ]
4-[3-methyl-7-(1-methyl-1H-pyrazol-3-yl)-3,4-dihydroisoquinolin-2(1H)-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); In 1,4-dioxane; water; at 90℃;Inert atmosphere;	Step 2: 4-[3-Methyl- 7 -(I -methyl- lH-pyrazo/-3-yl)-3, 4-dihydroisoquinolin-2(lH)-yl]-6-(4- methylpiperazin-l-yl)pyrimidin-2-amim; A mixture of l-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-. H-pyrazole ( l 1.5 mg, 0.0518 mmol), 4-(7-bromo-3-methyl-3,4-dihydroisoquinolin-2(l H)-yl)-6-{4-methylpiperazin-l- yl)pyrimidin-2-amine (0.018 g, 0.043 mmol) (Peak 1, Example 49, Step 7). dichloro(bis{di-tert-butyl[4- (dimethylamino)phenyl]phosphoranyl})palladium (0.916 mg, 0.00129 mmol), and sodium carbonate (9.14 mg, 0.0862 mmol) in 1,4-dioxane (0.50 mL) and water (0.10 mL) was vacuumed and refilled with N2 for 3 times and then stirred at 90 0C overnight. The mixture was purified by RP-HPLC (pH = 10) to afford the desired product. LCMS (M+H)+: m/z = 419.3 .

Reference： [1]Patent: WO2010/75270,2010,A1 .Location in patent: Page/Page column 137-138

6
[ 1020174-04-2 ]
[ 1263185-81-4 ]
9-tert-butyl-2-(1-methyl-pyrazol-3-yl)-3-methoxy-13-(2-thienyl)-5,6,9,10,11,12-hexahydro-8H-azepino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With water; potassium carbonate; In 1,2-dimethoxyethane; at 150℃; for 1h;Inert atmosphere; Microwave irradiation;	9-tert-butyl-2-((1-methyl-pyrazol)-3-yl)-3-yl)-3-methoxy-13-(2-thienyl)-5,6,9,10,11,12-hexahydro-8H-azepino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8-one (4h) A solution of 67 mg of 4e, 55 mg of K2CO3 and 56 mg of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl-1H-pyrazole in 3 ml of degassed 90% aq. dimethoxyethane was heated in a microwave oven under N2 atmosphere for 1 hr at 150 C. The reaction mixture was diluted with water and the product was extracted into ethyl acetate. The organic layer was washed, dried, concentrated and the product was purified by preparative HPLC, using a gradient of CH3CN-water. The product fractions were pooled and freeze-dried, to give 17 mg of 4h. MS-ESI: [M+1] 501.4. NMR (CDCl3) delta 1.53 (s, 9, tertC4H9), 1.90 (m, 2, CH2), 2.60, 3.16, 3.44 and 5.51 (4t, 8, 4CH2) 3.88 and 3.90 (2s, 6, N-CH3+OCH3), 6.77 and 7.63 (2s, 2, Ar-H), 7.28 and 7.34 (2s, 2, pyrazole-H), 6.98, 7.18 and 7.45 (3m, 3, thiophene-H).

Reference： [1]Patent: US2011/28450,2011,A1 .Location in patent: Page/Page column 18

7
[ 1020174-04-2 ]
(1r,4r)-2-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate [ No CAS ]
(1r,4r)-2-methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(2-methoxyethoxy)cyclohexanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate monohydrate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 150℃; for 16h;Inert atmosphere;	( 1 r,4r)-2~methoxyethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3 -(6- chloropyridin-3 -yl)pyrazolo [ 1 ,5-a]pyrimidin-5-yl)- 1 -(2- methoxyethoxy)cycIo exanecarboxylate (627 mg, 0.82 mmol) in dioxane (8 mL) and water (1 mL) was treated with boronate (256.4 g, 1.23 mmol), Pd(dppf)Ci2.CH2Cl2 (68.14 mg, 0.082 mmol) and Kappa3RhoOmicron? (567.2 mg, 2.46 mmol) under argon and heated at 150C for 16 h. Upon cooling, the mixture was filtered through Celite and the filtrate was evaporated off under reduced pressure to give crude residue which was purified by column chromatography (Si02, 0· 40% hexane-EtOAc) to provide desired product (lr,4r)~2-methoxyethyl 4-(7-(bis((2- (trimethylsilyl)ethoxy)methyl)amino)-3 -(6-( 1 -methyl- 1 H-pyrazol-3-yl)pyridin-3- yl)pyrazolo[l ,5-a]pyrimidin-5-yl)-l~(2-methoxyethoxy)cyclohexanecarboxylate (696 mg). HPLC-MS tR-3.49 min (UV 25 nw). Mass calculated for formula C40H63N7O7Si2 809.43;observed MH+ (LCMS) 810.3 (m/z).

Reference： [1]Patent: WO2012/27234,2012,A1 .Location in patent: Page/Page column 70; 71

8
[ 844501-71-9 ]
[ 74-88-4 ]
[ 1020174-04-2 ]
[ 847818-74-0 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In acetonitrile; at 20℃; for 70h;	EXAMPLE 7Synthesis of Obtained [2-(1-methyl-1H-pyrazol-3-yl)-[1,8]naphthyridin-4-yl]-pyridin-4-yl-amine (no. 35) and [2-(2-Methyl-2H-pyrazol-3-yl)-[1,8]naphthyridin-4-yl]-pyridin-4-yl-amine (no. 36) To a solution of 10.6 g (54.7 mmol) <strong>[844501-71-9]3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole</strong> in 100 ml acetonitrile, 17.8 g (54.7 mmol) caesium carbonate were added and the mixture stirred at ambient temperature for 70 hrs. The reaction mixture was filtered and the residue washed with acetonitrile. The combined filtrates were evaporated and taken into tert.butylmethylether. Undissolved material was filtered off; the filtrate was dried over sodium sulfate and evaporated. One got a mixture of 1-methyl-<strong>[844501-71-9]3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole</strong> und 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole as colorless, slowly crystallizing oil.

Reference： [1]Patent: US2012/316166,2012,A1 .Location in patent: Page/Page column 71

9
[ 1020174-04-2 ]
[ 1426135-85-4 ]
[ 1426133-19-8 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 12h;Inert atmosphere;	Methyl 3-(3-(3-(7-bromoimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (42) (40 mg, 0.078 mmol), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (19.6 mg, 0.094 mmol) and Pd(PPh3)4 (9 mg, 0.0078 mmol) were added to a flask equipped with a stir bar. The flask was evacuated and backfilled with nitrogen several times. DMF (1 mL) and 1.8 M K2CO3 (0.094 mmol) were added by syringe. The flask was sealed and heated at 80 C. for 12 hours. The reaction was filtered and directly purified by preparative reverse phase HPLC to afford methyl 3-(3-(4-methyl-3-(7-(1-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F56). MS m/z 513.2 (M+1)+.

Reference： [1]Patent: US2013/59832,2013,A1 .Location in patent: Paragraph 0564-0565

10
[ 1020174-04-2 ]
[ 1432514-99-2 ]
[ 1432513-62-6 ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 24h;Sealed tube;	General procedure: Preparation of (i?)-5-Fluoro-3-(l-(3-(l-methyl-lH-pyrazol-3-yl phenyl)ethyl)-2-oxo-N-(1.2,4- thiadiazol-5-yl)-2,3-dihydrobenzof d1oxazole-6-sulfonamide (28-3)[0234] In a sealed vial, compound of Formula 28-2 (45 mg, 0.090 mmol), l-methyl-3-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (21 mg, 0.10 mmol), PdC12(dppf)-CH2C12 adduct (7.3 mg, 0.009 mmol), and cesium carbonate (88 mg, 0.270 mmol) were combined in dioxane (1 mL) and water (0.14 mL). The mixture was heated at 90 C for 24 hours. The mixture was diluted with dioxane (4 mL), filtered through a celite pad, and the filtrate was concentrated. The resulting residue was purified by reverse phase HPLC (20-100% MeCN in water with 0.1% TFA, CI 8 column) to yield 28-3 as a white solid. ? NMR ? (ppm)(DMSO-d): 8.50 (s, 1 H); 7.74 (d, J = 5.6 Hz, 1 H); 7.63 (s, 1 H); 7.52-7.46 (m, 5 H); 7.41 (d, J = 9.8 Hz, 1 H); 6.40 (d, J = 1.9 Hz, 1 H); 5.65 (q, J = 7.2 Hz, 1 H); 3.79 (s, 3 H); 1.91 (d, J = 7.2 Hz, 3 H). LRMS C21H18FN604S2 [M+H] calc 501.08, obs 501.0.

Reference： [1]Patent: WO2013/63459,2013,A1 .Location in patent: Paragraph 0234

11
[ 1020174-04-2 ]
7-bromo-N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide [ No CAS ]
[ 1426530-82-6 ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 1h;Inert atmosphere; Microwave irradiation;	Example 1.10N-(5-(2-(2,6-cis-Dimethylpiperidin-1 -yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1 - methyl-1 H-pyrazol-5-yl)imidazo[1 ,2-a]pyridine-3-carboxamidePdCI2(dppf).CH2CI2 adduct (39.5 mg, 0.048 mmol) was added to a mixture comprising 1 -methyl-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (commercially available) (212 mg, 1.017 mmol), 7-bromo-N-(5-(2-(2,6-cis- dimethylpiperidin-1 -yl)ethylcarbamoyl)-2-fluorophenyl)imidazo[1 ,2-a]pyridine-3- carboxamide (Intermediate 4C) (500 mg, 0.968 mmol), Cs2C03 (1262 mg, 3.87 mmol) in 1 ,2-dimethoxyethane (10 ml) and water (4.29 ml). The mixture was degassed thoroughly refilling with nitrogen (x3). The mixture was heated using microwave radiation at 100C for 1 hour. The water was removed by pipette and the organic portion was concentrated in vacuo. The residue was dissolved in MeOH and dry loaded onto silica. The crude product was purified by chromatography on silica eluting with 0-20% MeOH in DCM to afford the title compound. (See Table 1 for characterising data).

Reference： [1]Patent: WO2013/30802,2013,A1 .Location in patent: Page/Page column 80; 81

12
[ 1020174-04-2 ]
[ 1426530-70-2 ]
[ 1426530-94-0 ]

Yield	Reaction Conditions	Operation in experiment
		step 2: 4-Fluoro-3-[7-(2-methyl-2H-pyrazol-3-yl)-imidazo[1 ,2-a]pyridine-3-carbonyl]- amino}-benzoic acid3-[(7-Bromo-imidazo[1 ,2-a]pyridine-3-carbonyl)-amino]-4-fluoro-benzoic acid methyl ester (step 1 )(1200 g, 3.060 mol), 1-methyl-3-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-1 H-pyrazole (commercially available) (764 g, 3.67 mol),PdCI2(dppf CH2Cl2 (75.0 g, 91.8 mmol) in dioxane (10 L) and aqueous Na2C03 (2 N, 4.6 L) were heated to reflux for 6 hr. The reaction mixture was cooled to 50 C and filtered. The filtrate was heated to reflux, to which was added AcOH (600 g, 10.0 mol) was added dropwise. During the course of addition solids came out of solution to give pale pink slurry. After addition the mixture was slowly cooled to RT and filtered. To the filter cake was added dioxane (20 L) followed by heating to reflux to obtain a solution. The solution was cooled to RTand filtered to provide the title compound as a white solid;1H NMR (400 MHz, DMSO-d6) delta 4.00 (s, 3 H) 6.67 (s, 1 H) 7.46 (t, J=9.41 Hz, 1 H) 7.40 (d, J=7.03 Hz, 1 H) 7.54 (s, 1 H) 7.85 (d, J=2.26 Hz, 1 H) 7.99 (s, 1 H) 8.28 (d, J=6.27 Hz, 1 H) 8.67 (s, 1 H) 9.47 (d, J=7.03Hz, 1 H) 10.35 (s, 1 H).Rt 5.40 mins; MS m/z 380.1 {M+H}+; Method 10 min LC

Reference： [1]Patent: WO2013/30802,2013,A1 .Location in patent: Page/Page column 81; 82

13
[ 1020174-04-2 ]
C₂₁H₂₀BrFN₄O₃ [ No CAS ]
C₂₅H₂₅FN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium hydrogencarbonate; cesium fluoride; In 1,4-dioxane; water; at 120℃; for 0.333333h;Microwave irradiation;	Arylbromide 64a is prepared analogously to the procedure described in Example 63, Steps 1 , 3 and 4. In step 3, pyrazole 23f is used for the ketone formation. Compound 1043 is prepared using the conditions of general procedure D2, substituting K2C03 by NaHC03. Arylbromide 64a (90.0 mg, 0.13 mmol) is treated with 25a (83.9 mg, 0.40 mmol), NaHC03 (22.3 mg, 0.27 mmol) and CsF (60.6 mg, 0.40 mmol) and PdCI2dppf (10.9 mg, 0.013 mmol) in dioxane- H20 (4: 1 , 1.5 mL). The mixture is heated in the microwave at 120C for 20 min. The residue is purified by preparative HPLC to provide compound 1043.

Reference： [1]Patent: WO2013/91096,2013,A1 .Location in patent: Page/Page column 76

14
[ 1020174-04-2 ]
1-(3-bromo-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-[(1R)-1-phenylethyl]urea [ No CAS ]
(R)-1-(3-(1-methyl-1H-pyrazol-3-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; at 80℃; for 1h;Inert atmosphere;	Step 2: (R)- 1 -(3 -bromo- 1 -trityl- 1 H-pyrazolo [4,3 -c]pyridin-6-yl)-3 -(1 -phenylethyl)urea (36 mg, 0.060 mmol), l-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (18.6 mg, 0.090 mmol), PdCl2(dppf)-CH2Cl2 adduct (7.3 mg, 8.96 muiotaetaomicron), 1,4-dioxane (0.6 mL) and Na2C03 (0.08 mL, 0.160 mmol, 2M) were charged in a vial. The mixture was evacuated and purged with nitrogen six times and heated at 80 C for lh. The mixture was diluted with EtOAc, washed with water, brine, dried (Na2S04) and concentrated in vacuo to afford crude (R)-l-(3-(l-methyl-lH-pyrazol-3-yl)-l^ phenylethyl)urea, which was used as such in the next step. MS ESI calcd. For C3gH34N70 [M + H]+ 604, found 604.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; at 80℃; for 1h;Inert atmosphere;	R)-1-(3-bromo-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (36 mg, 0.060 mmol), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (18.6 mg, 0.090 mmol), PdCl2(dppf)-CH2Cl2 adduct (7.3 mg, 8.96 mumol), 1,4-dioxane (0.6 mL) and Na2CO3 (0.08 mL, 0.160 mmol, 2M) were charged in a vial. The mixture was evacuated and purged with nitrogen six times and heated at 80 C for 1h. The mixture was diluted with EtOAc, washed with water, brine, dried (Na2SO4) and concentrated in vacuo to afford crude (R)-1-(3-(1-methyl-1H-pyrazol-3-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea, which was used as such in the next step. MS ESI calcd. For C38H34N7O [M + H]+ 604, found 604.

Reference： [1]Patent: WO2013/63214,2013,A1 .Location in patent: Page/Page column 115
[2]Patent: EP2770987,2018,B1 .Location in patent: Paragraph 0399

15
[ 1020174-04-2 ]
[ 1581258-29-8 ]
[ 1581258-02-7 ]

Yield	Reaction Conditions	Operation in experiment
76%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 150℃; for 1h;Microwave irradiation;	Example 7: V-(2-(2,2-dimethyl-4-phenyltetrahydro-2H-pyran-4-yl)ethyl)-6-(1- methyl-1 H-pyrazol-3-yl)pyrazin-2-amine 2M K2C03 solution (aq, 104 muIota_, 28.7 mg, 0.208 mmol) was added to a solution of the compound of 11 (30 mg, 0.087 mmol), methyl-pyrazole-4-boronic acid pinacol ester (C43)(Boron Molecular, CAS: 761446-44-0, CAT: BM103) (36 mg, 0.173 mmol) and fefra/c/s(triphenylphosphine)palladium(0) (5 mg, 0.004 mmol) in dioxane (0.5 mL) and heated to 150C under microwave irradiation for 1 h. The solution was then concentrated and resuspended in methanol before being loaded onto a silica SCX cartridge. The cartridge was washed with methanol and the desired product was eluted upon addition of 2M NH3 in MeOH. Further purification by silica column chromatography (4 g, DCM:MeOH 0-2%; stains - UV, Dragendorff) fractions 51-57 resulted in isolation of the product as a clear oil. (25.8 mg, 0.066 mmol, 76%). Fractions 58-62 were also collected however they contained a slight impurity. 1 H NMR (MeOD, 500 MHz) delta 7.945 (bs, 1 H, ArCH), 7.858 (bs, 1 H, ArCH), 7.813 (bs, 1 H, ArCH), 7.36-7.47 (m, 5H, ArCH), 7.25-7.30 (m, 1 H, ArCH), 3.949 (s, 3H, NCH3), 3.80-3.89 (m, 1 H, OCH2), 3.72-3.80 (m, 1 H, OCH2), 3.16-3.26 (m, 1 H, CH2), 2.86- 2.96 (m, 1 H, CH2), 2.51-2.59 (m, 1 H, CH2), 2.27 -2.36 (m, 1 H, CH2), 1.88-1.98 (m, 1 H, CH2), 1.65-1.77 (m, 3H, CH2), 1.187 (s, 3H, CH3), 0.669 (s, 3H, CH3), NH not observed. LCMS m/z C23H29N50 ES+ (RT: 5.05 min) 393.3 [MH+ + 1] (20%), 392.3 [MH+] (100%).

Reference： [1]Patent: WO2014/41349,2014,A1 .Location in patent: Page/Page column 59

16
[ 1020174-04-2 ]
[ 27048-04-0 ]
6-(1-methyl-1H-pyrazol-3-yl)-3-nitropyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 120℃; for 0.833333h;Inert atmosphere; Microwave irradiation;	a) 6-(1 -Methyl- 1H-pyrazol-3-yl)-3-nitropyridin-2-amine (A87) A mixture of 2-amino-3-nitro-6-chloropyridine A44 (0.20 g, 1.1 mmol), Na2C03 (0.489 g, 4.61 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 --pyrazole A86 (0.312 g, 1.50 mmol) and PdCI2(dppf) DCM solvate (0.072 g, 0.086 mmol) in dioxane (9.5 ml_) and H20 (0.5 ml_) was degassed for 10 minutes under a stream of nitrogen. The mixture was irradiated in the microwave at 120 C for 50 minutes. The cooled mixture was evaporated under reduced pressure, then purified by silica gel chromatography (40 g silica cartridge, 0- 100% EtOAc in petroleum benzine 40-60 C) to give the title compound as a yellow solid (0.155 g, 61 %); H NMR (400 MHz, cf DMSO) delta 8.42 (d, J = 8.8 Hz, 1 H), 8.09 (br. s, 2H), 7.52 (d, J = 2.0 Hz, 1 H), 7.16 (d, J = 8.8 z, 1 H), 7.00 (d, J = 2.0 Hz, 1 H), 4.23 (s, 3H). LCMS-A: rt 5.63 min, m/z (positive ion) 220.1 [M+H]+.

Reference： [1]Patent: WO2014/128465,2014,A1 .Location in patent: Page/Page column 98

17
[ 1020174-04-2 ]
[ 1225278-68-1 ]
[ 1225278-37-4 ]

Yield	Reaction Conditions	Operation in experiment
1.062 g	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In water; N,N-dimethyl-formamide; at 90℃; for 4h;Inert atmosphere;	A solution of Example A21 (1.177 g, 4.31 mmol) and <strong>[1020174-04-2]1-methyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (1.166 g, 5.60 mmol) in DMF (16 mL) was treated with Cs2CO3 (4.21 g, 12.93 mmol) and water (5 mL), sparged with Ar, treated with Pd(PPh3)4 (0.249 g, 0.215 mmol) and heated at 90 C. for 4 h. The mixture was cooled to RT, diluted with 4:1 EtOAc/THF, washed with 10% LiCl (2), then brine (1), dried over MgSO4, evaporated under reduced pressure and purified via silica gel chromatography (EtOAc/Hex) to yield 5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline as a tan solid (1.062 g, 77%). 1H NMR (400 MHz, DMSO-d6): delta 8.31 (d, 1H), 8.24 (s, 1H), 7.95 (s, 1H), 7.20 (d, 1H), 7.13 (d, 1H), 6.92 (d, 1H), 6.52 (dd, 1H), 5.49 (s, 2H), 3.84 (s, 3H); MS (ESI) m/z: 319.1 (M+H+).

Reference： [1]Patent: US2014/315917,2014,A1 .Location in patent: Paragraph 0317

18
[ 1020174-04-2 ]
2-bromo-6-(4-chlorophenyl)-1-isopropyl-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one [ No CAS ]
6-(4-chlorophenyl)-1-isopropyl-2-(1-methyl-1H-pyrazol-3-yl)-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 7h;Inert atmosphere;	To a solution of 2-bromo-6-(4-chlorophenyl)- 1 -isopropyl-5-(1 -methyl-6-oxo- 1 ,6-dihydropyridin-3- yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one (Step 19.4) (100 mg, 0.22 mmol) in dioxane (2 mL) and water (0.2 mL) under nitrogen were added 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-pyrazole (Step 21.1) (58.6 mg, 0.28 mmol), 052003 (183 mg, 0.563 mmol) and PdCI2(dppf).CH2CI2 adduct (26.5 mg, 0.03 mmol). The resulting mixture was flushed with Ar, heated up and stirred at 100 00 for 3 hr. The reaction was cooled down to RT, 1-methyl- 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (43 mg) and PdCI2(dppf).CH2CI2 adduct (20 mg) were added and the resulting mixture was heated up and stirred at 100 00 for 105 mm. The reaction mixture was diluted with EtOAc and water and both phases were separated. The aq. layer was extracted twice with EtOAc. Combined extracts were washed with brine, dried over Na2504, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (gradient 5-100 % CH3CN in 20 mm) followed by basic workup and trituration in iPr2O to afford the title product (44 mg, 44 % yield) as pale beige crystals. tR: 0.82 mm (LC-MS 2); ESl-MS: 463 [M+H] (LC-MS 2).The title compound was prepared in analogy to the procedure described in Example 21 using 2- bromo-6-(4-chlorophenyl)- 1 -isopropyl-5-(1 -methyl-6-oxo- 1 ,6-dihydropyridin-3-yl)-5,6- dihydropyrrolo[3,4-d]imidazol-4(1 H)-one (Step 19.4) and 1-methyl-3-(4,4,5,5-tetramethyl-1 3,2- dioxaborolan-2-yl)-1H-pyrazole (Step 22.1) at 100 00 for 7 hr. tR: 0.87 mm (LC-MS 2); ESl-MS:463 [M+H] (LC-MS 2).

Reference： [1]Patent: WO2014/191894,2014,A1 .Location in patent: Page/Page column 92; 93

19
[ 151049-87-5 ]
[ 73183-34-3 ]
[ 1020174-04-2 ]

Yield	Reaction Conditions	Operation in experiment
44.19%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 95℃; for 5h;Inert atmosphere;	Intermediate 702: 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole Compound 701 (0.2 g, 1.24 mmol) was dissolved in 5 ml of 1,4-dioxane, added with 0.378 g (1.49 mmol) of bis(pinacolato)diboron, 0.365 g (3.72 mmol) of potassium acetate, and 0.11 g (0.124 mmol) of [1,1-bis(di-phenylphosphino)ferrocene]palladium chloride dichloromethane complex under the protection of nitrogen, heated to 95 C and reacted for 5 h, and then cooled to room temperature. 15 mL of water was added, stirred for 1 h, and filtered to afford 0.114 g of solid. Yield: 44.19%.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 120℃; for 3h;Microwave irradiation;	A mixture of 3-bromo-1-methyl-1H-pyrazole obtained in Step A (400 mg), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (694 mg), (1,1'-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (101 mg), potassium acetate (488 mg) and 1,4-dioxane (5.0 mL) was heated with microwave irradiation at 120C for 3 hr. The insoluble substance was removed by filtration, and the solvent was evaporated under reduced pressure to give the title compound as a crude product. 1H NMR (400 MHz, CDCl3) delta 1.27 (12H, s), 3.98 (3H, s), 6.66 (1H, d, J = 2.0 Hz), 7.38 (1H, d, J = 2.0 Hz).

Reference： [1]Patent: EP3072893,2016,A1 .Location in patent: Paragraph 0394; 0395
[2]Patent: EP2818473,2014,A1 .Location in patent: Paragraph 0578

20
[ 1020174-04-2 ]
3-amino-7-bromo-5-(3-methylbutan-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one [ No CAS ]
3-amino-5-(3-methylbutan-2-yl)-7-(1-methyl-1H-pyrazol-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 120℃; for 1h;Microwave irradiation;	A mixture of 3-amino-7-bromo-5-(3-methylbutan-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one obtained in Step G (332 mg), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (347 mg), tetrakis(triphenylphosphine)palladium(0) (128 mg), aqueous sodium carbonate solution (2 M, 1.11 mL) and N,N-dimethylformamide (6.0 mL) was heated with microwave irradiation at 120C for 1 hr. The reaction mixture was cooled to room temperature, and poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate), and then HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)). To the obtained fraction was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (36.0 mg). 1H NMR (400 MHz, CDCl3) delta 0.82 (3H, d, J = 6.8 Hz), 1.08 (3H, d, J = 6.8 Hz), 1.39 (3H, d, J = 6.8 Hz), 1.88-1.97 (1H, m), 3.96 (3H, s), 4.77 (2H, brs), 4.84-4.94 (1H, m), 6.42 (1H, d, J = 2.4 Hz), 7.31 (1H, s), 7.39 (1H, d, J = 2.4 Hz), 10.44 (1H, brs). MS (ESI+) : [M+H]+301.2

Reference： [1]Patent: EP2818473,2014,A1 .Location in patent: Paragraph 0609; 0617

21
[ 1020174-04-2 ]
2-(3-amino-7-bromo-4-oxo-1,4-dihydro-5H-pyrazolo[4,3-c]pyridin-5-yl)-3-fluorobenzonitrile [ No CAS ]
2-(3-amino-7-(1-methyl-1H-pyrazol-3-yl)-4-oxo-1,4-dihydro-5H-pyrazolo[4,3-c]pyridin-5-yl)-3-fluorobenzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 1.5h;Microwave irradiation; Inert atmosphere;	A mixture of 2-(3-amino-7-bromo-4-oxo-1,4-dihydro-5H-pyrazolo[4,3-c]pyridin-5-yl)-3-fluorobenzonitrile obtained in Step G (160 mg), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (191 mg), tetrakis(triphenylphosphine)palladium(0) (53 mg), aqueous sodium carbonate solution (2 M, 0.460 mL) and N,N-dimethylformamide (10 mL) was heated with microwave irradiation at 130C for 90 min under argon atmosphere. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate/tetrahydrofuran. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (basic silica gel, methanol/ethyl acetate) to give a crude product. The crude product was crystallized from ethyl acetate/diethyl ether to give the title compound (44 mg). MS (ESI+): [M+H]+ 350.2. 1H NMR (400 MHz, CDCl3) delta 3.98 (3H, s), 4.75 (2H, s), 6.39 (1H, d, J = 2.4 Hz), 7.29 (1H, s), 7.39 (1H, d, J = 2.4 Hz), 7.51-7.68 (3H, m), 10.75 (1H, brs).

Reference： [1]Patent: EP2818473,2014,A1 .Location in patent: Paragraph 0700; 0715

22
[ 1020174-04-2 ]
5-bromo-1-(1-cyclopropylethyl)-4-methoxy-2-oxo-1,2-dihydropyridine-3-carbonitrile [ No CAS ]
1-(1-cyclopropylethyl)-4-methoxy-5-(1-methyl-1H-pyrazol-3-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 1h;Microwave irradiation; Inert atmosphere;	A mixture of 5-bromo-1-(1-cyclopropylethyl)-4-methoxy-2-oxo-1,2-dihydropyridine-3-carbonitrile obtained in Step B of Example 163 (66 mg), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (69 mg), tetrakis(triphenylphosphine)palladium(0) (26 mg), aqueous sodium carbonate solution (2 M, 0.666 mL) and 1,2-dimethoxyethane (3.0 mL) was heated with microwave irradiation at 100C for 1 hr under argon atmosphere. The reaction mixture was cooled to room temperature, and poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), and then silica gel column chromatography (basic silica gel, hexane/ethyl acetate) to give the title compound (26 mg). MS (ESI+) : [M+H]+ 299.3.

Reference： [1]Patent: EP2818473,2014,A1 .Location in patent: Paragraph 0750; 0751

23
[ 1020174-04-2 ]
5-bromo-1-(sec-butyl)-4-methoxy-2-oxo-1,2-dihydropyridine-3-carbonitrile [ No CAS ]
1-(sec-butyl)-4-methoxy-5-(1-methyl-1H-pyrazol-3-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 1h;Microwave irradiation;	To a mixture of 5-bromo-1-(sec-butyl)-4-methoxy-2-oxo-1,2-dihydropyridine-3-carbonitrile obtained in Step B (130 mg), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (114 mg), 2M aqueous sodium carbonate solution (1.37 mL) and 1,2-dimethoxyethane (2.5 mL) was added tetrakis(triphenylphosphine)palladium(0) (52.7 mg), and the mixture was stirred with microwave irradiation at 100C for 1 hr. The reaction mixture was diluted with water, and the mixture was extracted twice with ethyl acetate. The extracts were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (basic silica gel, ethyl acetate/hexane) to give the title compound (90 mg). MS (ESI+) : [M+H]+ 287.0.

Reference： [1]Patent: EP2818473,2014,A1 .Location in patent: Paragraph 0762

24
[ 1020174-04-2 ]
trifluoro-methanesulfonic acid 3-(3,3-dimethyl-morpholine-4-carbonyl)-7-methoxy-1-(1-methyl-1H-pyrrol-3-yl)-4,5-dihydro-imidazo[1,5-a]quinolin-8-yl ester [ No CAS ]
(3,3-dimethyl-morpholin-4-yl)-[7-methoxy-8-(1-methyl-1H-pyrazol-3-yl)-1-(1-methyl-1H-pyrrol-3-yl)-4,5-dihydro-imidazo[1,5-a]quinolin-3-yl]-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; dichloromethane; water; at 120℃;	To trifluoro-methanesulfonic acid 3- (3 ,3-dimethyl-morpholine-4-carbonyl)-7-methoxy- 1- (1- methyl- 1H-pyffol-3-yl)-4,5-dihydro-imidazo[ 1 ,5-a]quinolin-8-yl ester (70.00 mg; 0.12 mmol; 1.00 eq.) suspended in dioxane (2.00 ml; 23.47 mmol; 190.65 eq.) and water (0.20 ml), was added 1 -Methyl-3- (4,4,5 ,5-tetramethyl- [1,3,2] dioxaborolan-2-yl)- 1 H-pyrazole (51.23 mg; 0.25 mmol; 2.00 eq.), [1,1 ?-bis(diphenylphosphino)ferrocene] dichloropalladium(ii), complex with dichloromethane (1:1) (20.11 mg; 0.02 mmol; 0.20 eq.), and cesium carbonate (120.34 mg; 0.37 mmol; 3.00 eq.). The reaction mixture was stuffed at 120 C overnight. The reaction mixture was purified by reverse phase prep-HPLC (35-45% CH3CN in 0.1 % NH4OH in H20) to afford (3,3- Dimethyl-morpholin-4-yl)- [7-methoxy-8-( 1-methyl- 1H-pyrazol-3-yl)- 1 -(1-methyl- 1H-pyrrol-3- yl)-4,5-dihydro-imidazo[1,5-a]quinolin-3-yl]-methanone (7 mg; 11 %) as a white solid.? H-NMR (DMSO-d6): oe 7.93 (s, 1H), 7.64 (s, 1H), 7.14 (s, 1H), 7.05 (s, 1H), 6.79 (s, 1H), 6.59 (s, 1H), 6.12 (s, 1H), 4.09 (s, 2H), 3.96-3.86 (m, 5H), 3.81 (s, 3H), 3.76-3.67 (m, 5H), 3.39 (s, 2H), 3.05 (s, 2H), 2.89 (s, 2H), 1.41 (s, 6H). LCMS: m/z = 501 [M+H]

Reference： [1]Patent: WO2014/209978,2014,A1 .Location in patent: Paragraph 00212

25
[ 1020174-04-2 ]
(1S,3S)-3-aminocyclopentan-1-ol hydrochloride [ No CAS ]
8-bromo-7-methoxy-1-(thiophen-3-yl)-1,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylic acid [ No CAS ]
7-methoxy-8-(1-methyl-1H-pyrazol-3-yl)-1-thiophen-3-yl-1,4-dihydro-chromeno[4,3-c]pyrazole-3-carboxylic acid ((1S,3S)-3-hydroxy-cyclopentyl)-amide [ No CAS ]
7-methoxy-8-(1-methyl-1H-pyrazol-3-yl)-1-thiophen-3-yl-1,4-dihydro-chromeno[4,3-c]pyrazole-3-carboxylic acid (1S,3S)-3-amino-cyclopentyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%; 4.2%		Step 2: To a mixture of 8-bromo-7-methoxy-l-thiophen-3-yl-l,4-dihydro- chromeno[4,3-c]pyrazole-3-carboxylic acid ((lS,3S)-3-hydroxy-cyclopentyl)-amide and 8- bromo-7-methoxy-l-thiophen-3-yl-l,4-dihydro-chromeno[4,3-c]pyrazole-3-carboxylic acid (lS,3S)-3-amino-cyclopentyl ester (120.00 mg; 0.24 mmol; 1.00 eq.) was added l-methyl-3- (4,4,5, 5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrazole (76.37 mg; 0.37 mmol; 1.50 eq.), palladium acetate (2.75 mg; 0.01 mmol; 0.05 eq.), dicyclohexyl-(2',6'-dimethoxy-biphenyl-2-yl)- phosphane (10.05 mg; 0.02 mmol; 0.10 eq.), potassium carbonate (101.46 mg; 0.73 mmol; 3.00 eq.), dioxane (4.00 ml) and water (0.40 ml). The reaction mixture was heated at 140 C for 18 h. The mixture was concentrated and a portion of it was purified by flash chromatography (KPNH, 80-100 % EtOAc/Hexanes, 0-20 % MeOH/EtOAc) to afford 7-methoxy-8-(l-methyl-lH- pyrazol-3-yl)-l-thiophen-3-yl-l,4-dihydro-chromeno[4,3-c]pyrazole-3-carboxylic acid ((1S,3S)- 3-hydroxy-cyclopentyl)-amide (78 mg, 65 %) as a white solid. The rest of the crude material was purified by reverse phase prep-HPLC (35-45 % CH3CN in 0.1 % NH4OH in H20) to afford 7- methoxy-8-(l-methyl-lH-pyrazol-3-yl)-l-thiophen-3-yl-l,4-dihydro-chromeno[4,3-c]pyrazole- 3-carboxylic acid (lS,3S)-3-amino-cyclopentyl ester (5 mg, 4.2 %) as a white solid. 1H-NMR (DMSO-d6): delta 7.94 (s, IH), 7.82 (s, IH), 7.60 (s, IH), 7.50 (s, IH), 7.33 (s, IH), 6.77 (s, IH), 6.50 (s, IH), 5.38 (s, 2H), 4.96 (s, IH), 3.85 (s, 3H), 3.78 (s, 3H), 3.63 (s, IH), 1.32 (d, 12H). m/z = 492 [M+H]+

Reference： [1]Patent: WO2014/209980,2014,A1 .Location in patent: Paragraph 00304; 00305

26
[ 1020174-04-2 ]
methyl 1-(3-bromophenyl)-5-iodo-indazole-3-carboxylate [ No CAS ]
methyl 1-(3-bromophenyl)-5-(1-methyl-1H-pyrazol-3-yl)-1H-indazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; lithium chloride; In 1,2-dimethoxyethane; water; at 60℃; for 18h;Inert atmosphere;	To a stirred solution of methyl 1-(3-bromophenyl)-5-iodo-indazole-3-carboxylate (250 mg, 0.5469 mmol) in 1,2-dimethoxyethane (4.7 mL) and water (1.5 mL) was added1-methyl-3-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)- lh-pyrazole (143.7 mg, 0.6563 mmol,1.2 equiv), 1,1 ?-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (22.8 mg, 0.02735 mmol, 0.05 equiv), lithium chloride (81.2mg, 1.914 mmol, 3.5 equiv), and sodium carbonate (318.8 mg, 3.008 mmol, 5.5 equiv) under nitrogen. The resulting solution was stirred for 18 hours at 60 C. The reaction mixture was concentrated under reduced pressure then was purified by silica gel column with heptane/isopropyl acetate (3:2). This resulted in 124mg (3 8%) of the title compound as a white solid. LC-MS (ES, m/z): 411, 413 [M+Hf.

Reference： [1]Patent: WO2015/25025,2015,A1 .Location in patent: Page/Page column 280; 281

27
[ 1020174-04-2 ]
methyl 1-(3-bromophenyl)-5-iodo-pyrazolo[3,4-b]pyridine-3-carboxylate [ No CAS ]
methyl 1-(3-bromophenyl)-5-(1-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; lithium chloride; In 1,2-dimethoxyethane; water; at 90℃; for 18h;Inert atmosphere;	A solution of methyl 1 -(3-bromophenyl)-5 -iodo-pyrazolo [3 ,4-b]pyridine-3 -carboxylate (100 mg, 0.2074 mmol) in 1,2-dimethoxyethane (1.78 mL) and water (0.56 mL) was combined with 1-methyl-3-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)- lh-pyrazole (136.3 mg, 0.62 mmol, 3 equiv), 1,1 ?-bis(diphenylphosphino)fenocene-palladium(II)dichloride dichioromethane complex (8.64 mg, 0.0 1037 mmol, 0.05 equiv), lithium chloride (30.78 mg, 0.7260 mmol, 3.5 equiv), and sodium carbonate (120.9 mg, 1.141 mmol, 5.5 equiv). Reaction vessel was sparged with nitrogengas and then heated to 90 C and left to for 18 hours. The reaction mixture was concentrated underreduced pressure then was purified by silica gel column with heptane/isopropyl acetate (3:1). Thisresulted in 74mg (86%) of the title compound as a white solid. LC-MS (ES, m/z): 412, 414[M+H] .

Reference： [1]Patent: WO2015/25025,2015,A1 .Location in patent: Page/Page column 282

28
[ 1020174-04-2 ]
7-bromo-N-(2-methoxy-1-(4-(trifluoromethoxy)phenyl)ethyl)-2-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydropyrido[2,3-b]-pyrazine-4(1H)-carboxamide [ No CAS ]
N-(2-methoxy-1-(4-(trifluoromethoxy)phenyl)ethyl)-7-(1-methyl-1H-pyrazol-3-yl)-2-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydropyrido[2,3-b]-pyrazine-4(1H)-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); In water; toluene; at 100℃; for 3h;Inert atmosphere;	D) N-(2-methoxy-1-(4-(trifluoromethoxy)phenyl)ethyl)-7-(1-methyl-1H-pyrazol-3-yl)-2-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydropyrido[2,3-b]-pyrazine-4(1H)-carboxamide To a mixture of 7-bromo-N-(2-methoxy-1-(4-(trifluoromethoxy)phenyl)ethyl)-2-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydropyrido[2,3-b]-pyrazine-4(1H)-carboxamide (100 mg) and 1-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane-1H-pyrazole (101 mg), tripotassium phosphate (103 mg) in a mixed solvent of toluene (1.51 mL) and water (0.10 mL) was added bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (11.4 mg) at room temperature, the reaction mixture was stirred at 100C for 3 hr under argon atmosphere. The reaction mixture was cooled to room temperature, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (72 mg). MS (API+): [M+H]+621.3.

Reference： [1]Patent: EP2848618,2015,A1 .Location in patent: Paragraph 0953

29
[ 1020174-04-2 ]
(4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide [ No CAS ]
(9S)-5-(1-methyl-1H-pyrazol-3-yl)-N-(pyrazin-2-yl)-1,6,8-triazatricyclo[7.2.1.0^2,7]dodeca-2⁽⁷⁾,3,5-triene-8-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47.7%	With potassium phosphate; bis(dibenzylideneacetone)-palladium(0); XPhos; In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere;	A suspension of (4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (0.350 g, 1.105 mmol), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.690 g, 3.31 mmol) and potassium phosphate tribasic (0.703 g, 3.31 mmol) in 1,4-dioxane (25 mL) and water (4 mL) degassed with argon at room temp for 15 minutes. Then, to above mixture was added X-phos (53 mg, 0.110 mmol) and Pd(dba)2 (0.032 g, 0.055 mmol) and was further degassed for 15 minutes. The reaction mixture was stirred 16 hours at 100 C. After completion of the reaction as indicated by TLC, cooled to 28 C. and was diluted with water (15 mL) and extracted with EtOAc (2×25 mL). The organic layer was washed with water followed by brine solution and dried over anhydrous sodium sulfate, filtered and filtrate was evaporated to get the crude residue (TLC eluent: 5% MeOH in DCM, Rf value: 0.3, UV active). The crude residue was purified by column chromatography using neutral alumina, and the product was eluted 50% ethyl acetate in pet ether to afford (4S)-7-(1-methyl-1H-pyrazol-3-yl)-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (0.192 g, 0.527 mmol, 47.7% yield) as off white solid, LCMS (m/z): 363.30 [M+H]+. 1H NMR (400 MHz, CDCl3): delta ppm 13.98 (s, 1H), 9.56 (d, J=1.32 Hz, 1H), 8.33-8.27 (m, 2H), 7.66 (d, J=8.11 Hz, 1H), 7.56-7.52 (m, 1H), 7.46 (d, J=2.19 Hz, 1H), 7.42 (d, J=2.41 Hz, 1H), 5.68 (dd, J=5.92, 3.29 Hz, 1H), 3.99 (s, 3H), 3.33-3.12 (m, 3H), 2.99 (dd, J=12.06, 3.29 Hz, 1H), 2.36-2.26 (m, 1H), 2.11-1.98 (m, 1H)
47.7%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; water; at 100℃; for 16h;	A suspension of (4,S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-l,4-methanopyrido[2,3- 6][l,4]diazepine-5(2H)-carboxamide (0.350 g, 1.105 mmol), l-methyl-3-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.690 g, 3.31 mmol) and potassium phosphate tribasic (0.703 g, 3.31 mmol) in 1,4-dioxane (25 mL) and water (4 mL) degassed with argon at room temp for 15 minutes. Then, to above mixture was added X- phos (53mg, 0.110 mmol) and Pd(dba)2 (0.032 g, 0.055 mmol) and was further degassed for 15 minutes. The reaction mixture was stirred 16 hours at 100 C. After completion of the reaction as indicated by TLC, cooled to 28 C and was diluted with water (15 mL) and extracted with EtOAc (2x 25 mL). The organic layer was washed with water followed by brine solution and dried over anhydrous sodium sulfate, filtered and filtrate was evaporated to get the crude residue (TLC eluent: 5%MeOH in DCM, Rf value: 0.3, UV active). The crude residue was purified by column chromatography using neutral alumina, and the product was eluted 50% ethyl acetate in pet ether to afford (4S)-7-(l-methyl-lH-pyrazol-3- yl)-N-(pyrazin-2-yl)-3,4-dihydro-l,4-methanopyrido[2,3-*][l,4]diazepine-5(2H)- carboxamide (0.192 g, 0.527 mmol, 47.7 % yield) as off white solid, LCMS (m/z): 363.30 [M+H]+. 1H NMR (400 MHz, CDC13): delta ppm 13.98 (s, 1 H), 9.56 (d, J = 1.32 Hz, 1 H), 8.33 - 8.27 (m, 2 H), 7.66 (d, J = 8.11 Hz, 1 H), 7.56 - 7.52 (m, 1 H), 7.46 (d, J= 2.19 Hz, 1 H), 7.42 (d, J = 2.41 Hz, 1 H), 5.68 (dd, J = 5.92, 3.29 Hz, 1 H), 3.99 (s, 3 H),3.33 - 3.12 (m, 3 H), 2.99 (dd, J= 12.06, 3.29 Hz, 1 H),2.36 - 2.26 (m, 1 H),2.11 - 1.98 (m, 1 H)

Reference： [1]Patent: US2015/152108,2015,A1 .Location in patent: Paragraph 1534; 1535; 1536
[2]Patent: WO2016/79709,2016,A1 .Location in patent: Page/Page column 542-543

30
[ 1020174-04-2 ]
methyl 2-((6-chloro-3-nitropyridin-2-yl)amino)acetate [ No CAS ]
methyl N-(6-(1-methyl-1H-pyrazol-3-yl)-3-nitropyridin-2-yl)glycinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.45 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,2-dimethoxyethane; water; at 50℃; for 1h;Inert atmosphere;	A mixture of methyl 2-((6-chloro-3-nitropyridin-2-yl)amino)acetate (2.05 g), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (2.258 g), cesium carbonate (5.44 g), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.611 g), 1,2-dimethoxyethane (50 mL) and water (10 mL) was stirred at 50C for 1 hr under nitrogen atmosphere. To the mixture was added NH silica gel, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (2.45 g). MS (API+): [M+H]+ 292.1.

Reference： [1]Patent: EP2873669,2015,A1 .Location in patent: Paragraph 0527

31
[ 1020174-04-2 ]
6-bromo-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide [ No CAS ]
N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 0.333333h;Sealed tube; Inert atmosphere; Microwave irradiation;	A suspension of 6-bromo-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2I--carboxamide (intermediate 315, 290 mg, 0.574 mmol),methylpyrazolboronicacid pinacol ester (190 mg, 0.886 mmol), PdCI2(dppf) (43 mg, 59 pmol) and saturated aqueous Na2CO3 (0.7 ml) in DME (2.1 ml) was sealed in a vial and purged with argon. The reaction mixture was stirred at 120 C for 20 mm in a microwave. The suspension was diluted with DCM and water, phases were separated and the aqueous layer was extracted with DCM (2x).The combined organic layers were dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (1-10%) in DCM, followed by another purification eluting with a gradient of MeOH (1-5%) in DCM. Product containing fractions were combined, evaporated and dried to yield the title compound as an orange resin.(UPLC-MS 3) tR 0.95 mm; ESI-MS 507.2 [M+H].

Reference： [1]Patent: WO2015/59668,2015,A1 .Location in patent: Page/Page column 157

32
[ 1020174-04-2 ]
[ 864262-97-5 ]
tert-butyl 2-fluoro-4-(1-methyl-1H-pyrazol-3-yl)benzylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.64 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; at 90℃;Inert atmosphere;	A solution of tert-butyl 4-bromo-2-fluorobenzylcarbamate (1.46 g), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (1.0 g), sodium carbonate (1.02 g) and (1,1-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.35 g) in 1,2-dimethoxyethane (13 mL)-water (4 mL) was stirred under an argon atmosphere at 90C overnight. The reaction solution was diluted with water and ethyl acetate, and the organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel chromatography (hexane-ethyl acetate) to give the title compound (0.64 g). 1H NMR (300 MHz, DMSO-d6) delta 1.39 (9H, s), 3.88 (3H, s), 4.17 (2H, d, J = 5.7 Hz), 6.72 (1H, d, J = 2.3 Hz), 7.26-7.34 (1H, m), 7.38 (1H, brs), 7.51 (1H, dd, J = 11.7, 1.5 Hz), 7.58 (1H, d, J = 7.9 Hz), 7.73 (1H, d, J = 2.1 Hz).
0.64 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	A mixture of tert-butyl 4-bromo-2-fluorobenzylcarbamate (1.46 g), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (1.0 g), sodium carbonate (1.02 g), (1,1-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.35 g) and DME (13 mL)-water (4 mL) was stirred under an argon atmosphere at 90C overnight. The reactionmixture was diluted with water and ethyl acetate, and the organic layer was separated, washed with saturated brine,dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel chromatography (ethylacetate/hexane) to give the title compound (0.64 g).1H NMR (300 MHz, DMSO-d6) delta 1.39 (9H, s), 3.88 (3H, s), 4.17 (2H, d, J = 5.7 Hz), 6.72 (1H, d, J = 2.3 Hz), 7.26-7.34(1H, m), 7.38 (1H, brs), 7.51 (1H, dd, J = 11.7, 1.5 Hz), 7.58 (1H, d, J = 7.9 Hz), 7.73 (1H, d, J = 2.1 Hz).

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 0471; 0472
[2]Patent: EP3144308,2017,A1 .Location in patent: Paragraph 0274

33
[ 1020174-04-2 ]
2-(4-bromobenzyl)-4-(2-fluoro-4-(trifluoromethyl)phenoxy)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one [ No CAS ]
4-(2-fluoro-4-(trifluoromethyl)phenoxy)-2-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.14 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	To a solution of 2-(4-bromobenzyl)-4-(2-fluoro-4-(trifluoromethyl)phenoxy)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (0.16 g) obtained in Reference Example 132 in DME (3 mL) -water (3 mL) were added <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.076 g), sodium carbonate (0.14 g) and (1,1-bis(diphenylphosphino)ferrocene)dichloropalladium(II) dichloromethane adduct (0.027 g), and the mixture was stirred under an argon atmosphere at 90C overnight. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by NH silica gel chromatography (hexane-ethyl acetate), and solidified with diisopropyl ether to give the title compound (0.014 g). MS: [M+H]+ 483.1 1H NMR (300 MHz, DMSO-d6) delta 3.87 (3H, s), 4.51 (2H, s), 4.73 (2H, s), 6.67 (1H, d, J = 2.3 Hz), 7.34 (2H, d, J = 8.1 Hz), 7.42 (1H, d, J = 5.1 Hz), 7.61-7.81 (5H, m), 7.92 (1H, d, J = 10.8 Hz), 8.23 (1H, d, J = 5.1 Hz).

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 1268; 1269

34
[ 1020174-04-2 ]
[ 123843-67-4 ]
2,6-difluoro-4-(1-methyl-1H-pyrazol-3-yl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.14 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	To a solution of 4-bromo-2,6-difluorobenzonitrile (0.50 g) in DME (3 mL)-water (3 mL) were added <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.62 g), sodium carbonate (0.73 g), and (1,1-bis(diphenylphosphino)ferrocene)dichloropalladium(II) methylene chloride adduct (0.19 g), and the mixture was stirred under a nitrogen atmosphere at 90C overnight. The reaction mixture was diluted with water and ethyl acetate, and the organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by NH silica gel chromatography (hexane-ethyl acetate) to give the title compound (0.14 g). MS: [M+H]+ 220.1 1H NMR (300 MHz, CDCl3) delta 3.97 (3H, s), 6.58 (1H, d, J = 2.6 Hz), 7.41-7.50 (3H, m).

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 0619; 0620

35
[ 1020174-04-2 ]
2-(4-bromo-2-fluorobenzyl)-4-((2-fluorobenzyl)oxy)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one [ No CAS ]
4-((2-fluorobenzyl)oxy)-2-(2-fluoro-4-(1-methyl-1H-pyrazol-3-yl)benzyl)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.11 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 3h;Inert atmosphere;	To a solution of 2-(4-bromo-2-fluorobenzyl)-4-((2-fluorobenzyl)oxy)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (0.30 g) obtained in Reference Example 184 in DME (2 mL)-water (2 mL) were added <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.18 g), sodium carbonate (0.29 g), and (1,1-bis(diphenylphosphino)ferrocene)dichloropalladium(II) methylene chloride adduct (0.055 g), and the mixture was stirred under a nitrogen atmosphere at 90C for 3 hr. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by NH silica gel chromatography (hexane-ethyl acetate), and solidified with ethyl acetate-diisopropyl ether to give the title compound (0.11 g). MS: [M+H]+ 447.1 1H NMR (300 MHz, CDCl3) delta 3.94 (3H, s), 4.32 (2H, s), 4.83 (2H, s), 5.68 (2H, s), 6.50 (1H, d, J = 2.3 Hz), 6.97 (1H, d, J = 5.3 Hz), 7.05 (1H, t, J = 9.3 Hz), 7.11-7.20 (1H, m), 7.22-7.31 (1H, m), 7.34-7.45 (2H, m), 7.47-7.57 (2H, m), 7.74 (1H, t, J = 7.0 Hz), 8.26 (1H, d, J = 5.1 Hz).

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 1334; 1335

36
[ 1020174-04-2 ]
2-(4-bromobenzyl)-4-(2-fluoro-4-(2-hydroxypropan-2-yl)phenoxy)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one [ No CAS ]
4-(2-fluoro-4-(2-hydroxypropan-2-yl)phenoxy)-2-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.027 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 1h;Inert atmosphere;	A solution of 2-(4-bromobenzyl)-4-(2-fluoro-4-(2-hydroxypropan-2-yl)phenoxy)-1H-pyrrolo[3,9-c]pyridin-3(2H)-one (0.070 g) obtained in Reference Example 271, <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.040 g), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (0.012 g) and 2M aqueous sodium carbonate solution (0.28 mL) in DME (2 mL) was stirred under an argon atmosphere at 90C for 1 hr. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by NH silica gel chromatography (hexane-ethyl acetate). The obtained solid was recrystallized from hexane-ethyl acetate to give the title compound (0.027 g). MS: [M+H]+ 473.2 1H NMR (300 MHz, DMSO-d6) delta1.46 (6H, s), 3.87 (3H, s), 4.49 (2H, s), 4.72 (2H, s), 5.18 (1H, s), 6.67 (1H, d, J = 2.3 Hz), 7.23-7.31 (1H, m), 7.31-7.37 (4H, m), 7.41 (1H, dd, J = 12.4, 2.0 Hz), 7.72 (1H, d, J = 2.3 Hz), 7.77 (2H, d, J = 8.3 Hz), 8.20 (1H, d, J = 5.1 Hz).

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 1476; 1477

37
[ 1244041-71-1 ]
[ 1020174-04-2 ]
C₁₆H₁₈N₄O₂S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3189 - 3193

38
[ 1020174-04-2 ]
1,5-anhydro-3-O-(2-(4-bromobenzyl)-3-oxo-2,3-dihydro-1H-isoindol-4-yl)-2-deoxy-threo-pentitol [ No CAS ]
1,5-anhydro-3-O-(2-(4-bromobenzyl)-3-oxo-2,3-dihydro-1H-isoindol-4-yl)-2-deoxy-threo-pentitol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.040 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	To a solution of optically active 1,5-anhydro-3-O-(2-(4-bromobenzyl)-3-oxo-2,3-dihydro-1H-isoindol-4-yl)-2-deoxy-threo-pentitol (tR2) (0.12 g) obtained in Example 268 in DME (3 mL)-water (1 mL) were added 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2--yl)-1H-pyrazole (0.072 g), sodium carbonate (0.061 g) and (1,1-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.021 g), and the mixture was stirred under an argon atmosphere at 90C overnight. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by NH silica gel chromatography (hexane-ethyl acetate) to give the title compound (0.040 g). MS: [M+H]+ 420.2 1H NMR (300 MHz, DMSO-d6) delta 1.55-1.71 (1H, m), 2.07-2.18 (1H, m), 3.16-3.23 (1H, m), 3.41-3.45 (1H, m), 3.54-3.65 (1H, m), 3.78-3.92 (5H, m), 4.30-4.42 (3H, m), 4.68 (2H, s), 6.65 (1H, d, J = 2.3 Hz), 7.14 (2H, t, J = 7.6 Hz), 7.29 (2H, d, J = 8.1 Hz), 7.44-7.54 (1H, m), 7.69-7.79 (3H, m), OH proton was merged with H2O signal.

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 1216; 1217

39
[ 1020174-04-2 ]
1,5-anhydro-2-O-(2-(4-bromobenzyl)-3-oxo-2,3-dihydro-1H-isoindol-4-yl)-2-deoxy-threo-pentitol [ No CAS ]
1,5-anhydro-9-O-(2-(4-bromobenzyl)-3-oxo-2,3-dihydro-1H-isoindol-4-yl)-2-deoxy-threo-pentitol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.024 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	To a solution of optically active 1,5-anhydro-2-O-(2-(4-bromobenzyl)-3-oxo-2,3-dihydro-1H-isoindol-4-yl)-4-deoxy-threo-pentitol (tR4) (0.065 g) obtained in Example 271 in DME (3 mL)-water (1 mL) were added <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.039 g), sodium carbonate (0.033 g) and (1,1-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.011 g), and the mixture was stirred under an argon atmosphere at 90C overnight. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by NH silica gel chromatography (hexane-ethyl acetate), and solidified with THF-ethyl acetate-hexane to give the title compound (0.024 g). MS: [M+H]+ 420.2 1H NMR (300 MHz, DMSO-d6) delta 1.42-1.56 (1H, m), 1.96-2.09 (1H, m), 3.41-3.50 (2H, m), 3.73-3.89 (5H, m), 3.97-4.05 (1H, m), 4.07-4.15 (1H, m), 4.32 (2H, s), 4.67 (2H, s), 6.65 (1H, d, J = 2.3 Hz), 7.10-7.19 (2H, m), 7.25-7.33 (2H, m), 7.44-7.54 (1H, m), 7.67-7.79 (3H, m), OH proton was merged with H2O signal.

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 1218; 1219

40
[ 1020174-04-2 ]
4-((2-(4-bromo-2-fluorobenzyl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)oxy)-3,5-difluorobenzonitrile [ No CAS ]
3,5-difluoro-4-((2-(2-fluoro-4-(1-methyl-1H-pyrazol-3-yl)benzyl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)oxy)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.0081 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃;Inert atmosphere;	A solution of ethyl 2-(4-cyano-2,6-difluorophenoxy)-4-formylnicotinate (0.30 g) obtained in Reference Example 229 and (4-bromo-2-fluorophenyl)methanamine (0.20 g) in THF (6 mL) was stirred at room temperature for 4 hr. The reaction mixture was concentrated, to a solution of the residue in acetic acid (6 mL) was added sodium triacetoxyhydroborate (0.29 g) at room temperature, and the mixture was stirred under an argon atmosphere at room temperature for 2 hr. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution, and the mixture was diluted with ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. To a solution of the obtained residue (0.23 g), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.11 g) and 2M aqueous sodium carbonate solution (0.73 mL) in DME (4 mL) was added [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.036 g), and the mixture was stirred under an argon atmosphere at 80C overnight. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was crudely purified by silica gel chromatography (hexane-ethyl acetate), and solidified with ethyl acetate to give the title compound (0.0081 g). MS: [M+H]+ 476.1 1H NMR (300 MHz, CDCl3) delta 3.95 (3H, s), 4.42 (2H, s), 4.87 (2H, s), 6.52 (1H, d, J = 2.3 Hz), 7.17 (1H, d, J = 5.3 Hz), 7.35 (2H, d, J = 6.6 Hz), 7.39 (1H, d, J = 2.1 Hz), 7.41-7.48 (1H, m), 7.53 (1H, s), 7.55-7.58 (1H, m), 8.14 (1H, d, J = 5.1 Hz).

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 1425; 1426

41
[ 1020174-04-2 ]
2-(4-bromobenzyl)-4-(2,4-difluoro-6-methylphenoxy)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one [ No CAS ]
4-(2,4-difluoro-6-methylphenoxy)-2-(4-(1-methyl-1H-pyrazol-3-yl)benzyl)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.055 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 1h;Microwave irradiation;	To a solution of 2-(4-bromobenzyl)-4-(2,4-difluoro-6-methylphenoxy)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (0.10 g) obtained in Reference Example 213 and <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.070 g) in DME (3 mL) were added 2M aqueous sodium carbonate solution (0.5 mL) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.0092 g), and the mixture was stirred under microwave irradiation at 150C for 1 hr. The reaction mixture was diluted with water, extracted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by NH silica gel chromatography (hexane-ethyl acetate) to give the title compound (0.055 g). MS: [M+H]+ 447.0 1H NMR (300 MHz, DMSO-d6) delta 2.14 (3H, s), 3.87 (3H, s), 4.49 (2H, s), 4.73 (2H, s), 6.67 (1H, d, J = 2.3 Hz), 7.11 (1H, d, J = 9.4 Hz), 7.21-7.31 (1H, m), 7.31-7.39 (3H, m), 7.72 (1H, d, J = 2.3 Hz), 7.78 (2H, d, J = 8.1 Hz), 8.19 (1H, d, J = 5.3 Hz).

Reference： [1]Patent: EP2921480,2015,A1 .Location in patent: Paragraph 1368; 1369

42
[ 1020174-04-2 ]
5-bromo-2-fluoro-4-(trifluoromethyl)benzoic acid [ No CAS ]
2-fluoro-5-(1-methyl-1H-pyrazol-3-yl)-4-(trifluoromethyl)benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In water; toluene; at 50 - 90℃; for 20h;	Step B: 2-Fluoro-5-(l-methyl-lH-pyrazol-3-yl)-4-(trifluoromethyl)benzoic acidTo a deoxygenated mixture of 5-bromo-2-fluoro-4-(trifluoromethyl)benzoic acid (5.0 g, 17 mmol), l-(methyl)-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (4.35 g, 20.9 mmol) and K3PO4 (1 1.1 g, 52.3 mmol) in toluene (55 mL) and H20 (7 mL) was added 1, 1'- bis(di-tert-butylphosphino)ferrocene palladium dichloride (1.14 g, 1.74 mmol). The resulting mixture was heated at 90 C for 2 h, and then stirred at 50 C for 18 h. The mixture was cooled and filtered. The filtrate was concentrated and the residue was partitioned between water (200 mL) and EtOAc (300 mL). The aqueous layer was acidified to pH 5 with aqueous HC1 solution (I ) and the resulting precipitate was collected and dried to give the title compound. MS: mlz = 289 (M + 1). 'H NMR (400 MHz, DMSO-d6) delta 13.85 (s, 1H), 8.11 (d, 1H), 7.82 (m, 2H), 6.45 (s, 1H), 3.92 (s, 3H).
	With potassium phosphate; dichloro[1,1?-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P?]palladium; In water; toluene; at 80 - 90℃; for 20h;	To a deoxygenated mixture of 5-bromo-2-fluoro-4-(trifluoromethyl)benzoic acid (5.0 g,17 mmol), 1 -(methyl)-3-(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1 H-pyrazole (4.35 g, 20.9 mmol) and K3P04 (11.1 g, 52.3 mmol) in toluene (55 mL) and H20 (7 mL) was added 1,1?-bis(di-tert-butylphosphino)fenocene palladium dichloride(i.14 g, 1.74 mmol). The resultingmixture was heated at 90 C for 2 h, and then stined at 50 C for 18 h. The mixture was cooled and filtered. The filtrate was concentrated and the residue was partitioned between water (200mL) and EtOAc (300 mL). The aqueous layer was acidified to pH 5 with aqueous HC1 solution (1 N) and the resulting precipitate was collected and dried to give the title compound. MS: m/z =289 (M + 1). ?H NMR (400 MHz, DMSO-d6) oe13.85 (s, 1H), 8.11 (d, 1H), 7.82 (m, 2H), 6.45 (s,1H), 3.92 (s, 3H).

Reference： [1]Patent: WO2015/148344,2015,A2 .Location in patent: Page/Page column 97; 98
[2]Patent: WO2016/161572,2016,A1 .Location in patent: Page/Page column 67; 68

43
[ 1020174-04-2 ]
2-chloro-8-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)-1,6-naphthyridine [ No CAS ]
8-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)-2-(1-methyl-1H-pyrazol-5-yl)-1,6-naphthyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In water; acetonitrile; at 120℃; for 1h;Microwave irradiation;	Example 175 8-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)-2-(1-methyl-1H-pyrazol-5-yl)-1,6-naphthyridine (7) 2-chloro-8-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)-1,6-naphthyridine (20 mg, 0.062 mmol), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (15.57 mg, 0.075 mmol) and Pd(dppf)Cl2.CH2Cl2 (2.55 mg, 3.12 mumol) were loaded in a microwave vial then degassed sodium carbonate in water (175 mul, 0.087 mmol) and degassed acetonitrile (1075 mul) were added. The reaction mixture was heated at 120 C. for 60 min under microwave irradiation. The crude was purified via biotage column chromatography (Dichloromethane/EtOH 99.9/0.1 to 95/5) to give the title compound (15 mg, 66% yield). 1H NMR (500 MHz, CDCl3) ppm=9.26 (bs, 1H), 8.85 (bs, 1H), 8.39 (d, J=8.6, 1H), 7.90 (d, J=8.6, 1H), 7.87 (d, J=0.8, 1H), 7.76-7.73 (m, 2H), 7.72 (d, J=0.8, 1H), 7.65-7.61 (m, 2H), 7.56 (d, J=2.0, 1H), 6.87 (d, J=2.0, 1H), 4.15 (s, 3H), 4.01 (s, 3H). [M+H]+ 367. Rt 3.19 min (method N).

Reference： [1]Patent: US2016/16951,2016,A1 .Location in patent: Paragraph 0802; 0803

44
[ 1020174-04-2 ]
[ 84341-13-9 ]
8-(1-methyl-1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1388 - 1409

45
[ 1020174-04-2 ]
8-bromo-7-methoxy-1-(thiophen-3-yl)-1,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylic acid [ No CAS ]
7-methoxy-8-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-3-yl)-1,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 1h;Inert atmosphere; Microwave irradiation;	To a solution of 8-bromo-7-methoxy-1- (thiophen-3-yl) -1, 4-dihydrochromeno [4, 3-c] pyrazole-3-carboxylic acid (100 mg, 0.25 mmol) in dioxane/H2O (5/1, 2 mL) were added 1-methyl-3- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) -1H-pyrazole (104 mg, 0.50 mmol) , PdCl2(dppf) (36.6 mg, 0.05 mmol) and Cs2CO3 (161 mg, 0.50 mmol) at RT under nitrogen. The reaction mixture was stirred at 90 for 1h under MW conditions. The reaction mixture was then filtered through celite and washed with DCM (50 mL) . The filtrate was concentrated under vacuum the crude product was purified by HPLC (mobile phase: acetonitrile/water (10 mM NH4HCO3) to afford the desired compound (100 mg, 90 ) as an off-white solid. LCMS m/z409 [M+H]+

Reference： [1]Patent: WO2015/196759,2015,A1 .Location in patent: Paragraph 00266; 00267

46
[ 1020174-04-2 ]
8-bromo-N-(4-(tert-butyldiphenylsilyloxy)-2-methylbutan-2-yl)-1-(3,5-dimethoxyphenyl)-7-methoxy-N-methyl-1,4-dihydrochromeno[4,3-c]pyrazole-3-carboxamide [ No CAS ]
N-(4-(tert-butyldiphenylsilyloxy)-2-methylbutan-2-yl)-1-(3,5-dimethoxyphenyl)-7-methoxy-N-methyl-8-(1-methyl-1H-pyrazol-3-yl)-1,4-dihydrochromeno[4,3-c]pyrazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium hydrogencarbonate; In water; N,N-dimethyl-formamide; at 120℃; for 1h;Inert atmosphere; Microwave irradiation;	To a solution of 8-bromo-N- (4- (tert-butyldiphenylsilyloxy) -2-methylbutan-2-yl) -1-(3, 5-dimethoxyphenyl) -7-methoxy-N-methyl-1, 4-dihydrochromeno [4, 3-c] pyrazole-3-carboxamide (27 mg, 0.034 mmol) in DMF (1.5 mL) was added 1-methyl-3- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) -1H-pyrazole (21 mg, 0.10 mmol) , Pd (dppf) Cl2(4 mg, 0.0068 mmol) and NaHCO3(9 mg, 0.10 mmol) at RT under nitrogen. The reaction mixture was degassed with nitrogen for 20 min and water (0.3 mL) was added at RT. The reaction mixture was stirred at 120 for 1h under MW conditions. The reaction mixture was filtered through celite and washed with DCM (50 mL) . The filtrate was concentrated under vacuum the crude product was washed with water (10 ml) , brine (10 mL) and dried over sodium sulphate. The organic solvent was removed under vacuum the crude product was purified by preparative HPLC (C18, A 10 mmol NH4HCO3, B. CH3CN) to afford N- (4- (tert-butyldiphenylsilyloxy) -2-methylbutan-2-yl) -1- (3, 5-dimethoxyphenyl) -7-methoxy-N-methyl-8- (1-methyl-1H-pyrazol-3-yl) -1, 4-dihydrochromeno [4, 3-c] pyrazole-3-carboxamide (15 mg, 55 ) as a white solid. m/Z822.3 [M+Na]

Reference： [1]Patent: WO2015/196759,2015,A1 .Location in patent: Paragraph 00281; 00282

47
[ 1020174-04-2 ]
(4S)-N-(4-bromopyridin-2-yl)-7-(2-methylpyridin-4-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide [ No CAS ]
(9S)-N-[4-(1-methyl-1H-pyrazol-3-yl)pyridin-2-yl]-5-(2-methylpyridin-4-yl)-1,6,8-triazatricyclo[7.2.1.0^2,7]dodeca-2⁽⁷⁾,3,5-triene-8-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54.3%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 100℃; for 6h;	To a degassed solution of (4,S)-N-(4-bromopyridin-2-yl)-7-(2-methylpyridin-4-yl)-3,4- dihydro-l,4-methanopyrido[2,3-^][l,4]diazepine-5(2H)-carboxamide (200 mg, 0.443 mmol), l-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (138 mg, 0.665 mmol) and K3P04 (282 mg, 1.329 mmol) in 1,4-Dioxane (8 mL):Water (2 mL) was added PdCl2(dppf) (64.9 mg, 0.089 mmol) at room temperature and the reaction mixture was stirred at 100 C for 6 h. (TLC system: 5% Methanol in dichloro methane, R 0.2). The reaction mixture was poured in to cold water (10 mL) and extracted with ethyl acetate (2x50 mL). The combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to obtain crude compound. The crude compound was purified by flash column chromatography (Neutral alumina, 2% Methanol in DCM) to afford the desired product (45)-N-(4-(l-methyl-lH-pyrazol-3-yl)pyridin-2-yl)- 7-(2-methylpyridin-4-yl)-3,4-dihydro-l,4-methanopyrido[2,3-^][l,4]diazep ine-5(2H)- carboxamide (110 mg, 0.241 mmol, 54.3 % yield) as an off white solid. LCMS (m/z): 453.14 [M+H]+, Rt = 1.49 min.1H NMR (400 MHz, CDC13): delta ppm 13.56 (s, 1 H), 8.67 - 8.58 (m, 2 H), 8.37 (d, J=5.26 Hz, 1 H), 8.23 (s, 1 H), 7.72 (dd, J=5.15, 1.43 Hz, 1 H), 7.62 (d, J=7.89 Hz, 1 H), 7.55 - 7.46 (m, 2 H), 7.41 (d, J=2.19 Hz, 1 H), 6.74 (d, J=2.19 Hz, 1 H), 5.73 (dd, J=5.92, 3.29 Hz, 1 H), 3.98 (s, 3 H), 3.14 - 3.37 (m, 3 H), 3.03 (dd, J=12.06, 3.29 Hz, 1 H), 2.76 (s, 3 H), 2.41 - 2.29 (m, 1 H), 2.19 - 2.03 (m, 1 H).

Reference： [1]Patent: WO2016/79709,2016,A1 .Location in patent: Page/Page column 587

48
[ 1020174-04-2 ]
4,6,7-trichloro-N-cyclopentylphthalazin-1-amine [ No CAS ]
6,7-dichloro-N-cyclopentyl-4-(1-methyl-1H-pyrazol-3-yl)phthalazin-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃; for 1h;	A mixture of Example 1 (90 mg, 0.284 mmol), phenylboronic acid (34.7 mg, 0.284 mmol), tetrakis(triphenylphosphine)palladium(0) (32.8 mg, 0.028 mmol) and K2C03 (118 mg, 0.853 mmol) in 1,4-dioxane/water (ratio: 4:1, Volume: 6 mL) was stirred at 80 C for 1 hour. The reaction was purified by reverse phase preparative [IPLC (Gilson 281: column Xbridge 21.2*250mm c18 with a gradient 25-55 % mobile phase B in mobile phase A; mobile phase A:water with 10 mM NH4HCO3 mobile phase B: acetonitrile) to give the title compound. Example 4 was prepared according to the procedure used for the synthesis of Example 2, substituting 1 -methyl-3 -(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1 H-pyrazole for phenylboronic acid. LCMS (Method C): m/z 362.1 (M+H), retention time: 2.02 minutes; ?H NIVIR (CDC13, 400 MHz) oe 9.57 (s, 1H), 7.84 (s, 1H), 7.44 (d, J 2.0 Hz, 1H), 7.11 (d, J= 2.4 Hz, 1H), 4.99 (d, J= 6.4 Hz, 1H), 4.76-4.68 (m, 1H), 4.04 (s, 3H), 2.36-2.26 (m, 2H), 1.82-1.63 (m, 4H), 1.62-1.57 (m, 2H).

Reference： [1]Patent: WO2016/123796,2016,A1 .Location in patent: Page/Page column 37; 38

49
[ 1020174-04-2 ]
[ 223463-13-6 ]
[ 811464-20-7 ]

Yield	Reaction Conditions	Operation in experiment
20.18%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 110℃; for 5h;Inert atmosphere;	Intermediate 703: 5-bromo-2-(1-methyl-1H-pyrazol-3-yl)pyridine Intermediate 702 (0.114 g, 0.548 mmol) was dissolved in 5 ml of 1,4-dioxane, added with 0.130 g (0.457 mmol) of Compound 105, 0.447 g (1.371 mmol) of cesium carbonate, 1 ml of water and 0.027 g (0.023 mmol) of tetrakis(triphenylphosphine)palladium under the protection of nitrogen, heated to 110 C and reacted for 5 h, and then cooled to room temperature. The dioxane was removed by evaporation, and the residue was dissolved in 20 ml of saturated sodium bicarbonate solution and 20 ml of dichloromethane, and the resulting solution was separated into two phases. The aqueous phase was extracted with dichloromethane, and the organic phases were combined, dried, evaporated to dryness to afford a crude product. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 3: 1) to afford 0.022 g of solid. Yield: 20.18%. LC-MS: 238,240 [M+1]+, tR= 1.866 min.

Reference： [1]Patent: EP3072893,2016,A1 .Location in patent: Paragraph 0396; 0397

50
[ 61676-62-8 ]
[ 92525-10-5 ]
[ 1020174-04-2 ]

Yield	Reaction Conditions	Operation in experiment
54%	With n-butyllithium; In tetrahydrofuran; at -65 - -50℃; for 2h;Inert atmosphere; Large scale;	The compound 3-iodo-1-methyl-1H-pyrazole (2000 g, 9.6 mol, 1.0 eq)Was dissolved in 8 L of dry tetrahydrofuran,Then, Isopropoxyboronic acid pinacol ester (2146.1 g, 11.5 mol, 1.2 eq) was added to the solution,The solution was cooled to -65 to -50 C,Under argon protection,Was added dropwise n-butyllithium (6.25L, 12.5mol, 1.3eq),After completion of the dropwise addition, the reaction was stirred for 2 h at this low temperature,An aqueous solution of hydrochloric acid (1 mol / L) was added to the reaction solution to quench the reaction,The reaction solution was extracted three times with ethyl acetate,The combined organic layers were dried over saturated brine and the organic phase was concentrated. 1-methyl-1H-pyrazol-3-boronic acid pinacol ester(1080.9 g, 0.24 mol),Yield 54.0%Purity 97% +.

Reference： [1]Patent: CN105669733,2016,A .Location in patent: Paragraph 0037; 0038; 0039; 0040

51
[ 1020174-04-2 ]
tert-butyl 6-chloropyrazine-2-carboxylate [ No CAS ]
tert-butyl 6-(1-methyl-1H-pyrazol-3-yl)pyrazine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.7 mg	With potassium phosphate; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); In N,N-dimethyl-formamide; at 90℃; for 12h;Inert atmosphere;	A mixture of tert-butyl 6-chloropyrazine-2-carboxylate (100 mg), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (126 mg), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (42.5 mg), tripotassium phosphate (198 mg) and N,N-dimethylformamide (3.0 mL) was stirred under an argon atmosphere at 90C for 12 hr. Water was added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (92.7 mg). 1H NMR (300 MHz, CDCl3) delta 1.66 (9H, s), 4.01 (3H, s), 7.07 (1H, d, J = 2.3 Hz), 7.44 (1H, d, J = 2.3 Hz), 9.07 (1H, s), 9.35 (1H, s).

Reference： [1]Patent: EP3061754,2016,A1 .Location in patent: Paragraph 0679

52
[ 1020174-04-2 ]
5-(3-bromo-2-chlorophenyl)-1,3-dihydrobenzimidazol-2-one [ No CAS ]
5-[2-chloro-3-(1-methylpyrazol-3-yl)phenyl]-1,3-dihydrobenzimidazol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 130℃; for 0.666667h;Inert atmosphere; Microwave irradiation;	To a soution of I -methy3-(44,5,5-tetramethy1 ,3,2-dioxaboroan-2-y-1 H-pyrazoe (48 mg, 0.23 mmo), potassium phosphate (66 mg, 031 mmofl, and 5-(3-bromo-2-choro- pheny)-1,3-dihydrobenzimidazo-2-one (50 mg, 0.15 mmo) in 4:1 dioxane:water (2.0mL) was added PdC2(dppf)-CH2C2 (II mg, 0.02 mmo) at once. The mixture was degassed with nitrogen for 10 minutes and then heated in a microwave at 130 C for 40 minutes. After coohng to rt, the reaction mixture was dHuted with water and extracted with DCM (x 3). The crude product was purified by flash coumn chromatography (Si02 0- 10% DCMIMeOH) to afford the tiDe compound (26 mg, 52% yie?d). MS (ES): mass cEicd, for C17H13CN4O, 324.1; rn/z found, 325.1 [M+H1. 1H NMR (500 MHz, DMSOd6):3 10.73 (s, I H), 10.70 (5, 1 H), 756 7.39 (m, 4H), 7.05 6.97 (m, 3H), 6.41 628 (ni,I H), 3.68 (5, 3H).

Reference： [1]Patent: WO2016/176449,2016,A1 .Location in patent: Page/Page column 181; 182

53
[ 1020174-04-2 ]
6-((6-chloropyridin-3-yl)methyl)-8-fluoro-3-((1S,2S)-2-hydroxycyclopentyl)-7-methyl-2,3-dihydro-4H-1,3-benzoxazin-4-one [ No CAS ]
8-fluoro-3-((1S,2S)-2-hydroxycyclopentyl)-7-methyl-6-((6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)methyl)-2,3-dihydro-4H-1,3-benzoxazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.07 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃;Inert atmosphere;	To a mixture of 6- ( ( 6-chloropyridin-3-yl) methyl) -8- fluoro-3- ( (IS, 2S) -2-hydroxycyclopentyl) -7-methyl-2, 3-dihydro-4H-1, 3-benzoxazin-4-one (0.12 g) , l-methyl-3- ( 4 , 4 , 5, 5- tetramethyl-1, 3, 2-dioxaborolan-2-yl) -lH-pyrazole (0.09 g) , 1, 1' -bis (diphenylphosphino) ferrocene palladium (II) chloride dichloromethane complex . (0.01 g) and DME (10 mL) was added 2 M aqueous sodium carbonate solution (0.31 mL) , and the mixture was stirred under an argon atmosphere at 80C overnight. The reaction mixture was diluted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) and solidified with ethanol to give the title compound (0.02 g). In addition, as the second crystal, the title compound (0.05 g) was obtained.XH N R (300 MHz, CDC13) delta 1.63-1.93 (4H, m) , 1.97-2.13 (2H, m) , 2.18 (3H, d, J = 2.5 Hz), 3.02 (1H, d, J = 3.6 Hz), 3.97 (3H, s), 3.99 (2H, s), 4.23 (1H, dt, J = 6.6, 3.2 Hz), 4.31-4.47 (1H, m) , 5.24 (2H, d, J = 1.7 Hz), 6.82 (1H, d, J = 2.3 Hz), 7.34- 7.48 (2H, m) , 7.59 (1H, s) , 7.80 (1H, d, J = 8.3 Hz), 8.44 (1H, d, J = 1.7 Hz) .

Reference： [1]Patent: WO2016/208775,2016,A1 .Location in patent: Paragraph 0384

54
[ 1020174-04-2 ]
6-((6-chloropyridin-3-yl)methyl)-8-fluoro-3-((1S,2S)-2-hydroxycyclopentyl)-7-methyl-2,3-dihydro-4H-1,3-benzoxazin-4-one [ No CAS ]
8-fluoro-3-((1S,2S)-2-hydroxycyclohexyl)-7-methyl-6-((6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)methyl)-2,3-dihydro-4H-1,3-benzoxazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.03 g	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃; for 0.833333h;Microwave irradiation;	To a mixture of 6- ( (6-chloropyridin-3-yl) methyl) -8- fluoro-3- ( (IS, 2S) -2-hydroxycyclohexyl) -7-methyl-2H- benzo[e] [1, 3] oxazin-4 (3H) -one (0.04 g) , l-methyl-3- ( 4 , 4 , 5 , 5- tetramethyl-1, 3, 2-dioxaborolan-2-yl ) -lH-pyrazole (0.03 g) , 2 M aqueous sodium carbonate solution (0.1 mL) and DME (3 mL) -water (0.3 mL) was added bis (di-tert-butyl ( 4- dimethylaminophenyl ) phosphine) dichloropalladium (II) (0.003 g) , and the mixture was subjected to microwave irradiation at 110C for 50 min. The reaction mixture was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) and solidified with ethanol to give the title compound (0.03 g) .XH N R (300 MHz, DMSO-d6) delta 1.15-1.32 (3H, m) , 1.54-1.72 (4H, m) , 1.86-1.99 (1H, m) , 2.19 (3H, d, J = 2.5 Hz), 3.47-3.65 (1H, m) , 3.90 (3H, s) , 3.92-3.99 (1H, m) , 4.05 (2H, s), 4.76 (1H, d, J = 5.5 Hz), 5.22-5.48 (2H, m) , 6.75 (1H, d, J = 2.3 Hz), 7.41- 7.45 (1H, m) , 7.51 (1H, dd, J = 8.1, 2.3 Hz), 7.74 (1H, d, J = 2.3 Hz), 7.82 (lH, dd, J = 8.1, 0.8 Hz), 8.42 (1H, d, J = 1.7 Hz) .

Reference： [1]Patent: WO2016/208775,2016,A1 .Location in patent: Paragraph 0417

55
[ 1020174-04-2 ]
8-chloro-6-((6-chloropyridin-3-yl)methyl)-3-((1S,2S)-2-hydroxycyclopentyl)-7-methyl-2,3-dihydro-4H-1,3-benzoxazin-4-one [ No CAS ]
8-chloro-3-((1S,2S)-2-hydroxycyclopentyl)-7-methyl-6-((6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)methyl)-2,3-dihydro-4H-1,3-benzoxazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.01 g	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃; for 0.833333h;Microwave irradiation;	To a mixture of 8-chloro-6- ( ( 6-chloropyridin-3- yl) methyl) -3- ( (IS, 2S) -2-hydroxycyclopentyl ) -7-methyl-2 , 3- dihydro-4H-l, 3-benzoxazin-4-one (0.04 g) , l-methyl-3- (4, 4, 5, 5- tetramethyl-1, 3, 2-dioxaborolan-2-yl) -lH-pyrazole (0.03 g) and 2 M aqueous sodium carbonate solution (0.09 mL) in DME (3 mL) - water (0.3 mL) was added bis (di-tert-butyl (4- dimethylaminophenyl) phosphine) dichloropalladium (II) (0.01 g) , and the mixture was subjected to microwave irradiation at 110C for 50 min. The reaction mixture was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) and solidified with ethyl acetate to give the title compound (0.01 g) .XH NMR (300 MHz, DMSO-d6) delta 1.35-1.71 (4H, m) , 1.72-1.97 (2H, m) , 2.33 (3H, s), 3.89 (3H, s) , 3.98-4.08 (1H, m) , 4.10 (2H, s) , 4.27-4.44 (1H, m) , 4.90 (1H, d, J = 5.1 Hz), 5.37 (2H, d, J = 2.3 Hz), 6.75 (1H, d, J = 2.3 Hz), 7.49 (1H, dd, J = 8.2, 2.4 Hz), 7.60 (1H, s), 7.74 (1H, d, J = 2.3 Hz), 7.82 (1H, d, J = 8.1 Hz), 8.42 (1H, d, J = 1.7 Hz) .

Reference： [1]Patent: WO2016/208775,2016,A1 .Location in patent: Paragraph 0431

56
[ 1020174-04-2 ]
tert-butyl 4-(5-(3-cyano-6-(((trifluoromethyl)sulfonyl)oxy)pyrazolo[1,5-a]pyridin-4-yl)pyridin-2-yl)piperazine-1-carboxylate [ No CAS ]
tert-butyl 4-(5-(3-cyano-6-(1-methyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyridin-4-yl)pyridin-2-yl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere; Sealed tube;	tert-Butyl 4-(5 -(3 -cyano-6-(((trifluoromethyl)sulfonyl)oxy)pyrazolo[ 1,5 -a]pyridin-4-yl)pyridin-2-yl)piperazine- 1 -carboxylate (Intermediate P14; 150 mg, 0.271 mmol), 1 -methyl-3 - (4,4, 5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1H-pyrazole (113 mg, 0.543 mmol), Pd(PPh3)4 (31.4 mg, 0.0271 mmol) and 2 M Na2CO3(aq) (679 tL, 1.36 mmol) in dioxane (2 mL) were combined in a pressure tube. The resulting reaction mixture was sparged with nitrogen and then sealed and heated at 100 C overnight. The reaction mixture was cooled to ambient temperature, then diluted with water (10 mL) and filtered. The solids were washed with water (2 x 5 mL) and Et20 (2 x 5 mL) and air dried to afford the title compound (108 mg, 82% yield). MS (apci) m/z = 485.2 (M+H).

Reference： [1]Patent: WO2017/11776,2017,A1 .Location in patent: Paragraph 001176; 001177; 001178

57
[ 1020174-04-2 ]
3-cyano-4-(4-(4-(3,3-dimethylbutanoyl)piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyridin6-yltrifluoromethane sulfonate [ No CAS ]
4-(4-(4-(3,3-dimethylbutanoyl)piperazin-1-yl)phenyl)-6-(1-methyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃; for 3h;Inert atmosphere;	In a pressure tube, 3 -cyano-4-(4-(4-(3 ,3 -dimethylbutanoyl)piperazin- 1- yl)phenyl)pyrazolo[ 1,5 -a]pyridin-6-yl trifluoromethanesulfonate (Intermediate P16; 20 mg, 0.036 mmol), 1 -methyl-3 -(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1H-pyrazole (15 mg, 0.073 mmol), Pd(PPh3)4 (4.2 mg, 0.0036 mmol) and 2 MNa2CO3(aq) (91 tL, 0.18 mmol) were combined in dioxane (0.2 mL), sparged with N2, sealed and heated at 100 C for 3 h. After cooling to ambient temperature and stirring overnight, the reaction mixture was diluted with water (1 mL) and extracted with DCM (3 x 5 mL). The combined organic extracts were concentrated in vacuo and purified by reverse phase chromatography (0-95% ACN/water) to afford the title compound (4.6 mg, 26% yield). MS (apci) m/z = 482.1 (M+H).

Reference： [1]Patent: WO2017/11776,2017,A1 .Location in patent: Paragraph 001291; 001292; 001293

58
[ 1020174-04-2 ]
5-((5-bromopyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde [ No CAS ]
2-methoxy-5-((5-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)methoxy)isonicotinaldehyde [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 321 - 326

59
[ 1020174-04-2 ]
rac-tert-butyl {1-[({6-bromo-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]-2-methylbutan-2-yl}carbamate [ No CAS ]
rac-tert-butyl {1-[({8-[(2,6-difluorobenzyl)oxy]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl}carbonyl)amino]-2-methylbutan-2-yl}carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 18h;Inert atmosphere; Sealed tube;	Example 41A rac-tert-Butyl {1-[({8-[(2,6-difluorobenzyl)oxy]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl}carbonyl)amino]-2-methylbutan-2-yl}carbamate A mixture of 100 mg (0.17 mmol) of rac-tert-butyl {1-[({6-bromo-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]-2-methylbutan-2-yl}carbamate (Example 5A), 43 mg (0.21 mmol) of <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole</strong>, 14 mg (0.017 mmol) of 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) dichloride/dichloromethane complex and 166 mg (0.51 mmol) of caesium carbonate in 0.5 ml of water and 2 ml of dioxane was degassed with argon for 5 min and stirred in a closed tube at 100 C. for 18 h. The reaction mixture was cooled to room temperature and the residue was partitioned between ethyl acetate and water. The organic phase was separated off, washed with saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated. The residue was purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate, gradient 0% to 50%). This gave 50 mg of the target product (50% of theory). LC-MS (Method A): Rt=3.11 min; m/z=583 (M+H)+ 1H-NMR (400 MHz, CDCl3): delta [ppm]=0.95 (t, 3H), 1.24 (s, 3H), 1.42 (s, 9H), 1.57-1.66 (m, 2H), 1.77-1.86 (m, 11H), 2.74 (s, 3H), 3.69-3.82 (m, 2H), 3.95 (s, 3H), 4.58 (s, 1H), 5.30 (s, 1H), 5.41 (s, 2H), 6.94 (dd, 3H), 7.20-7.24 (m, 1H), 7.34 (ddd, 1H), 7.67 (s, 1H), 7.77 (s, 1H), 9.21 (d, 1H).

Reference： [1]Patent: US2017/50961,2017,A1 .Location in patent: Paragraph 0997; 0998; 0999; 1000

60
[ 1020174-04-2 ]
4-((6-chloropyridin-3-yl)methyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5,6-dimethylpyridine-2-carboxamide [ No CAS ]
N-((1S,2S)-2-hydroxycyclohexyl)-5,6-dimethyl-4-((6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)methyl)pyridine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃;Inert atmosphere;	Example 74 N-((1S,2S)-2-hydroxycyclohexyl)-5,6-dimethyl-4-((6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)methyl)pyridine-2-carboxamide 4-((6-Chloropyridin-3-yl)methyl)-N-((1S,2S)-2-hydroxycyclohexyl)-5,6-dimethylpyridine-2-carboxamide (100 mg), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (111 mg), potassium carbonate (148 mg) and Pd(Ph3P)4 (30.9 mg) were stirred in a mixture of THF (5 mL) and water (0.5 mL) under an argon atmosphere at 80C overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to give the title compound (84.0 mg). 1H NMR (300 MHz, CDCl3) delta1.24-1.52 (4H, m), 1.78 (2H, d, J = 9.5 Hz), 2.02-2.17 (2H, m), 2.20 (3H, s), 2.53 (3H, s), 3.43-3.58 (1H, m), 3.65 (1H, d, J = 3.8 Hz), 3.72-3.88 (1H, m), 3.96 (3H, s), 4.05 (2H, s), 6.81 (1H, d, J = 2.2 Hz), 7.34-7.42 (2H, m), 7.79 (1H, d, J = 8.2 Hz), 7.90 (1H, s), 8.11 (1H, d, J = 7.6 Hz), 8.44 (1H, s).

Reference： [1]Patent: EP3156397,2017,A1 .Location in patent: Paragraph 0342

61
[ 1020174-04-2 ]
methyl 5-chloro-4-((6-chloropyridin-3-yl)methyl)-6-methylpicolinate [ No CAS ]
methyl 5-chloro-6-methyl-4-((6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)methyl)picolinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32.7 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃;Inert atmosphere;	Methyl 5-chloro-4-((6-chloropyridin-3-yl)methyl)-6-methylpicolinate (100 mg), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (100 mg), sodium carbonate (68.1 mg) and Pd(Ph3P)4 (18.6 mg) were stirred in a mixture of DME (1.5 mL) and water (0.3 mL) under a nitrogen atmosphere at 80C overnight. The reaction mixture was diluted with water, and extracted twice with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by HPLC to give the title compound (32.7 mg). MS (ESI+) : [M+H]+357.0.

Reference： [1]Patent: EP3156397,2017,A1 .Location in patent: Paragraph 0360

62
[ 1020174-04-2 ]
1-(2,2-diethoxyethyl)-2-oxo-1,2-dihydroquinolin-7-yl trifluoromethanesulfonate [ No CAS ]
1-(2,2-diethoxyethyl)-7-(1-methyl-1H-pyrazol-3-yl)-1,2-dihydroquinolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With potassium phosphate; chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); In tetrahydrofuran; water; at 20 - 40℃; for 73h;	1-(2,2-diethoxyethyl)-2-oxo-1 ,2-dihydroquinolin-7-yl trifluoromethanesulfonate 104a (500 mg, 1.22 mmol) was dissolved in THF (30 ml_)/water (7 ml_) and to this was added 1 -methyl-3-(tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (305 mg, 1.47 mmol), XPhos Pd G2 (48 mg, 0.06 mmol) and K3PO4 (518 mg, 2.44 mmol) The mixture was stirred at 40 C for 1 h then at room temperature over 72 h. The reaction was quenched with H2O (50 ml_), extracted with Et20 (2 x 50 ml_), dried (MgSCU) and the solvent evaporated to afford a yellow gum. This was purified via column chromatography, eluting with Et20 and then EtOAc to afford 1 -(2,2-diethoxyethyl)-7-(1 -methyl-1 H-pyrazol-3-yl)-1 ,2-dihydroquinolin-2-one 104b (280 mg, 64%) as a yellow gum which solidified on standing. LC-MS (Method A) 342.2 [M+H]+; RT 2.44 min; 1H NMR (Method C) (CDC ): delta ppm 7.86 (s, 2H), 7.76 (s, 1H), 7.68 (d, J= 9.2 Hz, 1 H), 7.50 (d, J = 8.4 Hz, 1 H), 7.32 (d, J = 8.4 Hz, 1 H), 6.63 (d, J = 9.2 Hz, 1 H), 4.82 (t, J = 5.3 Hz, 1 H), 4.45 (d, J = 5.3 Hz, 2H), 3.98 (s, 3H), 3.83 - 3.76 (m, 2H), 3.58 - 3.50 (m, 2H), 1.12 (t, J= 7.0 Hz, 6H).

Reference： [1]Patent: WO2017/137744,2017,A1 .Location in patent: Page/Page column 226; 227

63
[ 1020174-04-2 ]
C₃₃H₃₃BrN₈O₃ [ No CAS ]
N-(4-(4-amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl)-6-methyl-5-(1-methyl-1H-pyrazol-3-yl)-2-oxo-2H-[1,2'-bipyridine]-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; water; at 110℃; for 0.833333h;Sealed tube;	General procedure: Example 123. N-(4-(4-Amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl)-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-2H-[1,2?-bipyridine]-3-carboxamide (1326) (1327) In a sealed tube a mixture of 827 N-(4-(4-amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl)-5-bromo-6-methyl-2-oxo-2H-[1,2?-bipyridine]-3-carboxamide (8.0 mg, 0.012 mmol) (example 118, step 2), 635 (1-methyl-1H-pyrazol-5-yl)boronic acid (2.3 mg, 0.02 mmol), and 632 DIPEA (4.6 mg, 0.036 mmol) in 29 1,4-dioxane (200 muL) and 23 water (40 muL) was stirred together before 662 Pd(tBu3)2 (3.1 mg, 6 mumol) was added. The reaction mixture was sealed and then heated and stirred at 110 C. for 50 min, cooled to rt, diluted with DMF, and purified via pH 10 preparative LC/MS (MeCN/water with NH4OH) to give the desired 855 product as a white solid. LCMS calcd for C37H39N10O3(M+H)+: m/z=671.3. Found: 671.3. 1H NMR (500 MHz, DMSO) delta 11.74 (s, 1H), 8.74 (dd, J=4.9, 1.1 Hz, 1H), 8.38 (s, 1H), 8.18 (td, J=7.8, 1.9 Hz, 1H), 7.91 (s, 1H), 7.80 (d, J=8.6 Hz, 2H), 7.76 (d, J=7.9 Hz, 1H), 7.70-7.63 (m, 1H), 7.56 (d, J=1.8 Hz, 1H), 7.43 (d, J=8.6 Hz, 2H), 6.58 (s, 1H), 6.42 (d, J=1.9 Hz, 1H), 4.54 (d, J=11.9 Hz, 1H), 3.74 (s, 3H), 3.61 (s, 1H), 3.40 (t, J=11.9 Hz, 1H), 3.25-3.12 (m, 1H), 2.91 (p, J=6.8 Hz, 1H), 2.75-2.60 (m, 1H), 2.16-1.97 (m, 1H), 1.87 (s, 3H), 1.81-1.73 (m, 1H), 1.51 (d, J=13.9 Hz, 2H), 1.02 (t, J=6.6 Hz, 6H)

Reference： [1]Patent: US2017/275290,2017,A1 .Location in patent: Paragraph 1330; 1331

64
[ 1020174-04-2 ]
3-bromo-5-methyl-pyridine-2-carboxylic acid ethyl-[(S)-1-methyl-2-(5-trifluoromethyl-pyridin-2-yloxy)-ethyl]-amide [ No CAS ]
C₂₂H₂₄F₃N₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19 mg	With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; caesium carbonate; In 1,4-dioxane; at 110℃;Inert atmosphere;	To a solution of D-1 (45.0 mg, 0.10 mmol) and 20.1 (42.0 mg, 0.20 mmol) in dry 1 ,4-dioxane (2.0 ml_), Cs2C03 (98.0 mg, 0.30 mmol) is added. The mixture is degassed with argon and Pd- PEPPSI-IPent catalyst (9.00 mg, 0.01 mmol) is added. The reaction is heated to 1 10C and stirred overnight. After cooling, the reaction is passed through a SPE Thiol cartridge, concentrated, then diluted with DMF and directly purified by HPLC-MS (using a solvent gradient H20/ACN with NH4OH). Fractions are then lyophilized to afford 19 mg of Example 20. ESI pos.+neg. (Loop-lnj.): 448 [M+H]+; HPLC (Rt): 1 .07 (Method F).

Reference： [1]Patent: WO2017/178344,2017,A1 .Location in patent: Page/Page column 77

65
[ 1020174-04-2 ]
C₁₇H₁₇BrF₃N₃O₂ [ No CAS ]
C₂₁H₂₂F₃N₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17 mg	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 110℃;	To a solution of D-5 (30.0 mg, 0.07 mmol) and 34.1 (19.0 mg, 0.09 mmol) in dry 1 ,4-dioxane (2.0 mL), is added K2C03 (3N aq. solution, 93.0 muIota_, 0.30 mmol). The mixture is degassed with argon and Pd(dppf)CI2-DCM (6.00 mg, 0.01 mmol) is added. The reaction is heated to 1 10C and stirred overnight, then cooled and the mixture is passed through a SPE Thiol cartridge. The solution is concentrated and purified by HPLC-MS (using a solvent gradient H20/ACN with NH4OH) to afford 17 mg of Example 34. ESI pos.+neg. (Loop-lnj.): 434 [M+H]+; HPLC (Rt): 1.03 min (Method F).

Reference： [1]Patent: WO2017/178344,2017,A1 .Location in patent: Page/Page column 80

66
[ 1020174-04-2 ]
2-bromo-N-ethyl-N-[(S)-1-methyl-2-(5-trifluoromethylpyridin-2-yloxy)-ethyl]benzamide [ No CAS ]
C₂₂H₂₃F₃N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17 mg	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; at 80℃;Inert atmosphere;	A mixture of D-1 (43 mg, 0.10 mmol) in 1,4-dioxane (2.0 mL) is degassed for 15 mm with Argonand 74.1 (31 mg, 0.15 mmol) and 3 M K2003 (133 pL, 0.40 mmol) is added. The mixture isflushed with argon and Pd(dppf)Cl2DCM (8 mg, 0.01 mmol) is added and the reaction is stirred at 80C overnight. The mixture is filtered through a 1 mL SPE-Thiol-cartidge and basic alumina, washed with DMF/MeOH = 9/1 and purified by HPLC-MS (using a solvent gradient H20/ACN with NH4OH) to provide 17 mg of Exampie 74. ESI-MS: 433 [M+H] HPLC (Rt): 0.92 mm(Method T).

Reference： [1]Patent: WO2017/178340,2017,A1 .Location in patent: Page/Page column 92

67
[ 1020174-04-2 ]
C₁₈H₁₆ClF₆N₃O₂ [ No CAS ]
C₂₂H₂₁F₆N₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20 mg	With dichloro[1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II); caesium carbonate; In 1,4-dioxane; at 110℃;Inert atmosphere;	Step 4: To a stirred solution of 19.4 (45.6 mg, 0.10 mmol), 19.5 (41.6 mg, 0.20 mmol) andCs2CO3 (97.7 mg, 0.30 mmol) in dioxane (2.0 mL) under argon was added Pd-PEPPSI-l Pent catalyst (8.6 mg, 0.040 mmol) and the resulting mixture was stirred overnight at 110 C. The reaction mixture was filtered and purified by preparative HPLC (using a solvent gradientH20/ACN with NH4OH) to afford 20mg of Example 19 ESI-MS: 502 [M+H] HPLC (Rt): 1.13 and 1.15 mm (method C).

Reference： [1]Patent: WO2017/178343,2017,A1 .Location in patent: Page/Page column 50; 51

68
[ 1020174-04-2 ]
5-bromo-2-[[1-[3-(1,1-difluoroethyl)-4-fluorophenyl]triazol-4-yl]methoxy]pyrimidine [ No CAS ]
2-[[1-[3-(1,1-difluoroethyl)-4-fluorophenyl]triazol-4-yl]methoxy]-5-(1-methylpyrazol-3-yl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In tetrahydrofuran; water; at 100℃; for 1.5h;Microwave irradiation;	In a vial a suspension of 5-bromo-2-[[i-[3-(i ,i-difluoroethyl)-4-fluoro- phenyl]triazol-4-yl]methoxy]pyrimidine (Example 183, 25 mg, 0.060 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-i ,3,2-dioxaborolan-2-yl)-i H-pyrazole (15.07 mg,0.072 mmol), Na2003 (20 mg, 0.181 mmol) and PdCI2(dppf) (4 mg, 0.006 mmol) in THF/H20 (3 mL/0.3 mL) was capped and heated under microwave irridiation for 1 .5 h at 100 C. The completed reaction was diluted with EtOAc and washed with water, brine, dried (Na2504), filtered, and concentratedunder reduced pressure. Purification (FCC, 5i02, eluting with 0-50% EtOAc in hexanes) afforded the title compound (13.8 mg, 55%). MS (ESI): mass calcd.for C19H15F3N70, 415.1; m/zfound, 416.1 [M+H]. 1H NMR (400 MHz, ODd3)oe 8.96-8.90 (5, 2H), 8.17-8.12 (5, 1 H), 7.94-7.87 (m, 1 H), 7.87-7.79 (m,1 H), 7.46 - 7.39 (d, J = 2.3 Hz, 1 H), 7.36 - 7.27 (t, J = 9.4 Hz, 1 H), 6.55 -6.48 (d, J = 2.3 Hz, 1 H), 5.74 - 5.67 (d, J = 0.7 Hz, 2H), 4.06 - 3.90 (5, 3H),2.17- 1.96(m, 3H).

Reference： [1]Patent: WO2017/139428,2017,A1 .Location in patent: Page/Page column 222; 223

69
[ 1020174-04-2 ]
[ 16727-47-2 ]
2,6-bis(benzyloxy)-3-(1-methyl-1H-pyrazol-3-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67.4%	With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere;	To a stirred solution of 2,6-bis(benzyloxy)-3-bromopyridine (16-1) (177 mg, 480 mumol), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> 24-1 (100.0 mg, 480 mumol) and potassium phosphate (221 mg, 960 mumol) in water: dioxane (10 mL) was degassed with argon for 10 minute. PdCl2(dppf)-DCM (39.1 mg, 48.0 mumol) was added to above reaction mixture and the solution was again purged with argon and refluxed for 16 hour at 100C. After completion of the reaction was observed by TLC ( Rf = 0.5 in 30% EtOH/Hexane), the reaction mixture was filtered through celite and concentrated. The residue was again dissolved in EtOAc (50 mL), washed with water, brine and evaporated. The crude residue was purified by combi flash chromatography (4 g Isco gold, hexane/EtOAc 70-30%) to give 2,6-bis(benzyloxy)-3-(1-methyl- 1H-pyrazol-3-yl)pyridine 24-2 (120 mg, 323 mumol, 67.4 %) as a white gummy solid. 1H NMR (400 MHz, DMSO-d6) delta 8.17 (d, J = 8.2 Hz, 1H), 7.65 (d, J = 1.9 Hz, 1H), 7.46-7.42 (m, 4H), 7.39-7.33 (m, 4H), 7.33-7.31 (m, 2H), 6.61 (d, J = 2.1 Hz, 1H), 6.51-6.49 (m, 1H), 5.46 (s, 2H), 5.37 (s, 2H), 3.85 (s, 3H). Synthesis

Reference： [1]Patent: WO2017/197046,2017,A1 .Location in patent: Page/Page column 310; 311

70
[ 844501-71-9 ]
[ 74-88-4 ]
[ 1020174-04-2 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[844501-71-9]3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.5 g, 2.58 mmol, 1 eq) in DMF (5 mL) was added t-buOK (1 M, 5.15 mL, 2 eq). The mixture was stirred at 15 C for 10 min. Then MeI (1.10 g, 7.73 mmol, 481.25 uL, 3 eq) was added. The resulting mixture was stirred at 15 C for another 3 h. The reaction mixture was poured into H2O (10 mL), and extracted with EtOAc (10 mLx3). The combined organic layers were washed with brine (10 mLx2), dried over Na2SO4, filtered and concentrated under reduced pressure to afford the title compound (0.3 g, crude) as yellow oil, which was used into the next step without further purification.

Reference： [1]Patent: WO2018/13867,2018,A1 .Location in patent: Paragraph 684

71
[ 1020174-04-2 ]
(S)-tert-butyl 3-((4-(6-bromo-1-(phenylsulfonyl)-1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)piperidine-1-carboxylate [ No CAS ]
tert-butyl (3S)-3-[[4-[6-(1-methylpyrazol-3-yl)-1H-indol-3-yl]-5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere;	To a solution of tert-butyl (3S)-3-[[4-[1-(benzenesulfonyl)-6-bromo-indol-3-yl]-5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidine-1-carboxylate (0.15 g, 220.41 umol, 1 eq) in DMF (1 mL) and H2O (0.5 mL) was added <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole</strong> (91.72 mg, 440.83 umol, 2 eq), Na2CO3 (70.09 mg, 661.24 umol, 3 eq) and Pd(PPh3)4 (25.47 mg, 22.04 umol, 0.1 eq). The mixture was stirred under N2 at 130 C for 12 h. The reaction mixture was poured into H2O (10 mL), and extracted with EtOAc (10 mLx3). The combined organic layers were washed with brine (10 mLx3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (PE: EtOAc= 1:1) to afford the title compound (0.06 g, crude) as a white solid.

Reference： [1]Patent: WO2018/13867,2018,A1 .Location in patent: Paragraph 685

72
[ 1020174-04-2 ]
[ 873-75-6 ]
[ 179055-20-0 ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 2875 - 2894

73
[ 1020174-04-2 ]
N-(5-amino-2-bromo-4-methoxyphenethyl)-2,2,2-trifluoroacetamide [ No CAS ]
(5-amino-4-methoxy-2-(1-methyl-1H-pyrazole-4-yl)phenethyl)-2,2,2-trifluoroacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; In butan-1-ol; at 115℃;	N-(5-amino-2-bromo-4-methoxyphenethyl)-2,2,2-trifluoroacetamide (100 mg, 0.30 mmol) was dissolved in n-butanol (3 mL), to which 1-methylpyrazoleboronicacidpinacolester (61 mg, 0.3 mmol), SPhos (16.0 mg, 0.04 mmol), sodium carbonate (155 mg, 1.47 mmol), and Pd2(dba)3 (tris(dibenzylideneacetone)dipalladium(0), 16.0 mg, 0.02 mmol) were added while stirring. Gas was eliminated from the reaction mixture, followed by heating at 115 C. overnight. The reaction mixture was filtered with celite, washed with dichloromethane, concentrated under reduced pressure, and extracted with ethylacetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Then, purification was performed by silica gel column chromatography (eluent: ethylacetate/hexane, 1/1) to give the target compound (5-amino-4-methoxy-2-(1-methyl-1H-pyrazole-4-yl)phenethyl)-2,2,2-trifluoroacetamide as a brown oil (30.0 mg, 0.09 mmol, yield: 15%). 1H-NMR (300 MHz, CDCl3) delta 7.48 (s, 1H), 7.41 (s, 1H), 6.68 (s, 1H), 6.58 (s, 1H), 6.23 (s, br, 1H), 3.96 (s, 3H), 3.84 (s, 1H), 3.44 (q, J=7.2 Hz, 2H), 2.84 (t, J=7.2 Hz 2H)

Reference： [1]Patent: US2018/111905,2018,A1 .Location in patent: Paragraph 0337; 0338; 0339

74
[ 1020174-04-2 ]
[ 130284-52-5 ]
5-chloro-6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; water; at 100.0℃;Inert atmosphere;	Pd2(dba)3 (176.56 mg, 0.19 mmol) and Xphos (183.83 mg, 0.39 mmol) were added to a solution of <strong>[130284-52-5]6-bromo-5-chloropyridin-3-amine</strong> (800 mg, 3.86 mmol), 1 -methyl-3-(4,4,5,5-tetramethyl-i ,3,2-dioxaborolan-2-yl)-1H-pyrazole (1203.52 mg, 5.78 mmol) and K3P04 (2.456 g,11.57 mmol) in dioxane/H20 (6/1, 20 mE) under an N2 atmosphere. The mixture was stirred at 1000 C. overnight. The reaction solution was filtered and the filtrate was concentrated to give a crude product. The crude product was purified by column chromatography over silica gel (petroleum ether/ethyl acetate from 100/0 to 0/100). The desired fractions were collected and the solvent was concentrated under reduced pressure to afford 1 57a (530 mg, 5 9.0% yield) as a yellow solid. ECMS (ESI) mlz M+i: 209.1.

Reference： [1]Patent: US2018/170909,2018,A1 .Location in patent: Paragraph 0887; 0888; 1702; 1703

75
[ 1020174-04-2 ]
5,6-dichloro-2-methylpyridin-3-amine [ No CAS ]
5-chloro-2-methyl-6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; water; at 100℃;Inert atmosphere;	[1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complexed with dichloromethane (113 mg, 0.14 mmol) was added to a solution of 5,6-dichloro-2-methylpyridin-3-amine (350 mg, 1.98 mmol), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (535 mg, 2.57 mmol) and potassium acetate (582 mg, 5.93 mmol) in dioxane/water (3:1, 10 mL) under N2 atmosphere at 100 C. overnight. The mixture was filtered and the filtrate was concentrated to give a crude product. The crude product was purified by flash column chromatography over silica gel (eluent: petroleum ether/ethyl acetate from 100/0 to 0/100). The eluent was collected and the solvent was concentrated under reduced pressure to give the product as a yellow solid (315 mg, 72% yield). LC-MS: (ES, m/z): [M+1]+ 222.9.

Reference： [1]Patent: US2018/170909,2018,A1 .Location in patent: Paragraph 1791; 1792

76
[ 1020174-04-2 ]
[ 13600-46-9 ]
5-amino-2-(1-methyl-1H-pyrazol-3-yl)nicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51.3%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere;	5-Amino-2-chloronicotinonitrile, 12a (100 mg, 0.65 mmol), <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (135.5 mg, 0.65 mmol) and Na2CO3 (138.0 mg, 1.30 mmol) were added to a dioxane/water mixture (9:1, 6 mL) and the reaction was purged with N2. Pd(dppf)Cl2 (47.6, 0.065 mmol) was added and the reaction was stirred at 100 C. for 16 h. The reaction mixture was concentrated to dryness to give a crude black oil. The crude oil was purified by flash column chromatography over silica gel (dichloromethane/MeOH from 100/0 to 90/10) to afford 5-amino-2-(1-methyl-1H-pyrazol-3-yl)nicotinonitrile, 12b (100 mg, 51.3%) as a black solid. LCMS (ESI) m/z M+1: 200.1.

Reference： [1]Patent: US2018/170909,2018,A1 .Location in patent: Paragraph 0908; 0909

77
[ 1020174-04-2 ]
(S)-isopropyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2-methyl-6-(((trifluoromethyl)sulfonyl)oxy)pyridin-3-yl)acetate [ No CAS ]
(S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2-methyl-6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%		A mixture of (S)-isopropyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-S -(4-(4-fluorophenethoxy)phenyl)-2-methyl-6-(((trifluoromethyl)sulfonyl)oxy)pyridin-3 -yl)acetate (0.025 g, 0.034 mmol), 1 -methyl-3 -(4,4,5,5 -tetramethyl- 1,3 ,2-dioxaborolan-2- yl)-1H-pyrazole (0.0 14 g, 0.068 mmol), Pd(Ph3P)4 (7.82 mg, 6.77 .imol), and 2 M Na2CO3 (0.042 ml, 0.085 mmol) in toluene (1 mL) and ethanol (1 mL) was degassed. The reaction was heated at 90 C for 2 h. After cooling to ambient temperature, the reactionmixture was filtered through a pad of celite and concentrated in vacuo. The residue was taken up in ethanol (1 mL). 5 M NaOH (0.068 mL, 0.338 mmol) was added and the mixture was heated at 80 C for 3 h, cooled to ambient temperature and filtered. The cmde mixture was purified via preparative HPLC to afford the desired product (14.6 mg, 68%). ?H NMR (500 MHz, DMSO-d6) 7.40 - 7.33 (m, 3H), 7.14 (t, J= 8.6 Hz, 3H),7.01 - 6.94 (m, 2H), 6.83 (dd, J= 8.6, 2.4 Hz, 1H), 5.95 (br. s., 1H), 5.51 (d, J= 2.2 Hz,1H), 4.25 -4.13 (m, 2H), 3.72 (s, 3H), 3.23 (br. s., 1H), 3.03 (t, J= 6.6 Hz, 2H), 2.89 (t,J = 11.9 Hz, 1H), 2.55 (s, 4H), 2.20 (d,J= 11.4 Hz, 1H), 1.99- 1.90 (m, 2H), 1.51 (br. s., 1H), 1.30 (d,J= 16.1 Hz, 1H), 1.24- 1.13 (m, 11H), 1.03 (d,J= 12.1 Hz, 1H), 0.86 (s, 3H), 0.61 (s, 3H). LCMS (M+1) = 629.3.

Reference： [1]Patent: WO2018/127800,2018,A1 .Location in patent: Page/Page column 205

78
[ 1020174-04-2 ]
2,4-dichloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline [ No CAS ]
4-chloro-6-methoxy-2-(1-methyl-1H-pyrazol-3-yl)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 6518 - 6545

79
[ 23100-12-1 ]
[ 1020174-04-2 ]
6-(1-methyl-1H-pyrazol-3-yl)nicotinaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	To a mixture of 6-chloronicotinaldehyde (20.0 g) , 1- methyl-3- (4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl) -1H- pyrazole (32.32 g) , potassium carbonate (38.99 g) , DME (400 mL) and water (40 mL) was added PdCl2(dppf) dichloromethane adduct (3.45 g) at room temperature. Under an argon atmosphere, the reaction mixture was stirred overnight at 90C, diluted with ethyl acetate at room temperature, and added to water. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate and the solvent was (1299) evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (25.0 g) . (1300) 1H NMR (400 MHz, CDC13) delta 4.01 (3H, s) , 6.97 (1H, d, J = 2.45 Hz), 7.45 (1H, d, J = 2.45 Hz), 8.08 (1H, d, J = 8.4 Hz), 8.19 (1H, dd, J = 8.31, 1.96 Hz), 9.05 (1H, d, J = 1.47 Hz), 10.09 (1H, s).
		A) 6-(1-methyl-1H-pyrazol-3-yl)nicotinaldehyde The title compound was obtained from 6-chloronicotinaldehyde and <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> by a method similar to that in step F of Example 1. 1H NMR (400 MHz, CDCl3) delta 4.01 (3H, s), 6.97 (1H, d, J = 2.45 Hz), 7.45 (1H, d, J = 2.45 Hz), 8.08 (1H, d, J = 8.4 Hz), 8.19 (1H, dd, J = 8.31, 1.96 Hz), 9.05 (1H, d, J = 1.47 Hz), 10.09 (1H, s).

Reference： [1]Patent: WO2018/194181,2018,A1 .Location in patent: Paragraph 0236
[2]Patent: EP3643718,2020,A1

80
[ 3430-26-0 ]
[ 1020174-04-2 ]
5-bromo-4-methyl-2-(1-methyl-1H-pyrazol-3-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 18h;Inert atmosphere; Sealed tube;	Into a vial was weighed 2,5-dibromo-4-methylpyridine (300 mg, 1.20 mmol), 1-Methyl-1H-pyrazole-3-boronic acid pinacol ester (251 mg, 1.20 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (49.3 mg, 0.0600 mmol), and sodium carbonate (380 mg, 3.59 mmol). Under nitrogen, anhydrous 1,4-dioxane (6.0 mL) and water (1.2 mL) was added and the vial was sealed. The reaction mixture was stirred at 100 C. for 18 h. After cooling to rt, the reaction mixture was concentrated and the residue purified by flash column chromatography (100:0-40:60 heptanes/iPrOAc) to afford the target compound as a white solid (144 mg, 48%); 1H NMR (400 MHz, Chloroform-d) delta 8.62 (s, 1H), 7.81 (s, 1H), 7.40 (d, J=2.4 Hz, 1H), 6.84 (d, J=2.4 Hz, 1H), 3.97 (s, 3H), 2.43 (s, 3H).

Reference： [1]Patent: US2018/282328,2018,A1 .Location in patent: Paragraph 2277; 2278

81
[ 552330-86-6 ]
[ 1020174-04-2 ]
C₁₂H₁₁N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere;	A mixture of compound 5-bromoisoindolin-1-one(200 mg, 0.94 mmol, 1.0 eq), 1-methyl-3-(4,4,5,5-tetram-ethyl-i ,3,2-dioxaborolan-2-yl)- 1H-pyrazole (215 mg, 1.04mmol, 1.1 eq), cesium carbonate (922 mg, 2.83 mmol, 1.2eq), and Pd(dppf)C12 (21 mg, 0.03 mmol) in 1,4-dioxane(15mE) and water (2 mE) was stirred at 1000 C. for 16 hours under a nitrogen atmosphere. After cooling to room temperature, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (30%-100% EtOAc in PE) to give 4A (120 mg, 60% yield): ?H NMR (400 MHz, CDC13) oe 7.96 (s, 1H), 7.89 (d, J 0.8 Hz, 2H), 7.43 (d, J 2.2 Hz, 1H), 6.62 (d, J 2.3 Hz, 1H), 6.36 (s, 1H), 4.48 (s, 2H), 3.99 (s, 3H).

Reference： [1]Patent: US2018/291002,2018,A1 .Location in patent: Paragraph 0402; 0403

82
[ 675109-26-9 ]
[ 1020174-04-2 ]
C₁₂H₁₁N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;	A mixture of <strong>[675109-26-9]6-bromoisoindolin-1-one</strong> (287 mg, 1.35 mmol), 1-methyl-5-(tributylstannyl)-1H-imidazole (500 mg, 1.35 mmol), Pd(dppf)Cl2 (33 mg, 0.041 mmol) and Cs2CO3 (1.32 g, 4.05 mmol) in dioxane (50 mL) and water (8 mL) was heated to 100 C. overnight. After cooling, the mixture was concentrated under vacuum and purified by column chromatography on silica gel ((1%-3% MeOH in DCM) to afford 9A (220 mg, 76% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) delta 8.66 (s, 1H), 7.76-7.15 (m, 4H), 7.15 (s, 1H), 4.43 (s, 2H), 3.72 (s, 3H); ESI m/z 214.1 [M+1]+.

Reference： [1]Patent: US2018/291002,2018,A1 .Location in patent: Paragraph 0423; 0424

83
[ 1020174-04-2 ]
5-[(2,5-dichloropyrimidin-4-yl)amino]-3-(3-hydroxy-3-methylbutyl)-1-methylbenzimidazol-2-one [ No CAS ]
5-((5-chloro-2-(1-methyl-1H-pyrazol-3-yl)pyrimidin-4-yl)amino)-3-(3-hydroxy-3-methylbutyl)-1-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,4-dioxane; water; at 130℃; for 0.5h;Microwave irradiation;	A mixture of 5-[(2,5-dichloropyrimidin-4-yl)amino]-3-(3-hydroxy-3-methyl-butyl)-1- methyl-benzimidazol-2-one (intermediate D2a, 20 mg, 0.05 mmol), 1-methyl-3-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (12.6 mg, 0.06 mmol), sodium carbonate (1 1 mg, 0.10 mmol) and bis(triphenylphosphine)palladium (II) chloride (1.8 mg, 0.0025 mmol) in dioxane:water 1 : 1 (1 mL in total) was heated in the microwave at 130 C for 30 min. The mixture was partitioned between DCM and water and pH adjusted to 5 using 10% citric acid before separation and extraction with further DCM. The organic layers were combined and evaporated, and the resulting solution was purified by preparative HPLC (ACE 5 C18-PFP column (5mu, 250x21.2mm), 15 minute gradient elution from 40:60 to 25:75 water: methanol (both modified with 0.1 % formic acid) at a flow rate of 20ml_/min) to give yellow solid that required further purification by normal phase chromatography (0 to 6% MeOH in DCM, 10 g column) to obtain 5-[[5-chloro-2-(1-methylpyrazol-3-yl)pyrimidin-4-yl]amino]-3-(3-hydroxy-3- methyl-butyl)-1-methyl-benzimidazol-2-one (10 mg, 40%, 0.0204 mmol) as a solid. LCMS (Method T4) Rt 2.63 min, m/z 442.1738, expected 442.1753 for C21 H25CIN7O2 [M+H]+. 1 H NMR (500 MHz, acetone-de): delta 8.42-8.36 (1.4H, br m, including partly exchanged NH), 8.00 (1 H, d, J 2.0 Hz), 7.65 (1 H, br s), 7.48 (1 H, dd, J 8.4, 2.0 Hz), 7.08 (1 H, d, J 8.4 Hz), 6.88 (1 H, br s), 4.09 (2H, m), 3.98 (3H, s), 3.39 (3H, s), 1.90 (2H, m), 1.22 (6H, s). OH not observed.

Reference： [1]Patent: WO2018/215801,2018,A1 .Location in patent: Paragraph 00276

84
[ 1020174-04-2 ]
6-chloro-5-(8-chloroquinolin-6-yl)pyrazin-2-amine [ No CAS ]
5-(8-chloroquinolin-6-yl)-6-(1-methyl-1H-pyrazol-3-yl)pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 16h;	To a stirred solution of 6-chloro-5-(8-chloroquinolin-6-yl)pyrazin-2-amine (0.460 g, 1.57 mmol, 1.0 eq.) and <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.394 g, 1.89 mmol, 1.2 eq.) in dioxane (10 mL) was added Na2CO3 (0.334 g, 3.15 mmol, 2.0 eq.) and 2 mL water. Then reaction was purged with N2 for about 5 min. To this reaction mixture was added Pd(dppf)Cl2.DCM complex (0.129 g, 10 mol %) and N2 was purged again for another 5 min. Then reaction mixture was heated at 100 C. for 16 h, allowed to cool to RT and extracted using ethyl acetate (3*50 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum to obtain the solid residue which was purified by reversed phase column chromatography to afford the desired product as yellow solid (0.005 g, 1%). LCMS: 337[M+1]+. 1H NMR: (400 MHz, DMSO-d6) delta 8.97 (d, J=2.63 Hz, 1H), 8.39 (d, J=7.89 Hz, 1H), 7.97 (s, 2H), 7.76 (s, 1H), 7.66 (br. S, 1H), 7.61 (dd, J=4.17, 8.11 Hz, 1H), 6.72 (s, 2H), 6.26 (br. S, 1H), 3.71 (s, 3H).

Reference： [1]Patent: US2019/23666,2019,A1 .Location in patent: Paragraph 0580; 0581; 0582

85
[ 1020174-04-2 ]
6-chloro-5-(1H-indazol-5-yl)pyrazin-2-amine [ No CAS ]
5-(1H-indazol-5-yl)-6-(1-methyl-1H-pyrazol-3-yl)pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
6%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In sulfolane; at 100℃; for 16h;	To a stirred solution of 6-chloro-5-(1H-indazol-5-yl)pyrazin-2-amine (0.150 g, 0.61 mmol, 1.0 eq.) and <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.152 g, 0.73 mmol, 1.2 eq.) in dioxane (10 mL) was added Na2CO3 (0.129 g, 1.22 mmol, 2.0 eq.) and 2 mL water. Then reaction was purged with N2 for about 5 min. To this reaction mixture was added Pd(dppf)Cl2.DCM complex (0.025 g, 5 mol %) and N2 was purged again for another 5 min. The reaction mixture was heated at 100 C. for 16 h. After that reaction mixture was allowed to cool to RT and extracted using ethyl acetate (3*50 mL). The combined organic layers were washed (brine), dried (anhydrous Na2SO4) and concentrated under vacuum to get the solid residue which was purified by reversed phase column chromatography to afford the desired product as off white solid (0.010 g, 6%). LCMS: 292.2 [M+1]+. 1H NMR: (400 MHz, DMSO-d6) delta 13.01 (br. S, 1H), 8.01 (s, 1H), 7.90 (s, 1H), 7.69 (s, 1H), 7.53 (d, J=1.75 Hz, 1H), 7.40 (d, J=8.77 Hz, 1H), 7.25 (d, J=8.77 Hz, 1H), 6.48 (s, 2H), 5.89 (d, J=2.19 Hz, 1H), 3.74 (s, 3H).

Reference： [1]Patent: US2019/23666,2019,A1 .Location in patent: Paragraph 0586; 0587; 0588

86
[ 1020174-04-2 ]
[ 33332-28-4 ]
6-(1-methyl-1H-pyrazol-3-yl)pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 16h;	To a stirred solution of 6-chloropyrazin-2-amine (1 g, 7.72 mmol, 1.0 eq.) and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.76 g, 8.49 mmol, 1.1 eq.) in dioxane (40 mL) was added Na2CO3 (1.63 g, 15.4 mmol, 2.0 eq.) and 8 mL of water. The reaction mixture was purged with N2 for about 5 min and Pd(dppf)Cl2.DCM complex (0.315 g, 5 mol percent) was added. Reaction mixture was re-purged with N2 and heated at 100° C. for 16 h. Following this, reaction was allowed to cool to RT and extracted using ethyl acetate (3*150 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum to obtain the solid residue which was purified by normal phase column chromatography to afford the desired product as brown solid (0.380 g, 28percent).

Reference： [1]Patent: US2019/23666,2019,A1 .Location in patent: Paragraph 0601; 0602; 0603

87
[ 1020174-04-2 ]
[(2S,5'R)-7-chloro-1' ,4-dimethoxy-5'-methyl-3,3'-dioxospiro[benzofuran-2,6'-cyclohexene]-6-yl]trifluoromethanesulfonate [ No CAS ]
(2S,5'R)-7-chloro-3',4-dimethoxy-5'-methyl-6-(1-methylpyrazol-3-yl)spiro[benzofuran-2,4'-cyclohex-2-ene]-1',3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With potassium carbonate; In N,N-dimethyl-formamide;	(3b) (2S,5'R)-7-Chloro-3' ,4-dimethoxy-5'-methyl-6-(1-methylpyrazol-3-yl)spiro[benzofuran-2,4'-cyclohex-2-ene]-1',3-dione The compound of Example 3 (3a): [(2S,5'R)-7-chloro-1',4-dimethoxy-5'-methyl-3,3'-dioxo-spiro[benzofuran-2,6'-cyclohexene]-6-yl] trifluoromethanesulfonate (76 mg) was dissolved in N,N-dimethylformamide (1.6 mL). To this, <strong>[1020174-04-2]1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.0403 g), potassium carbonate (0.0669 g) and [1,1'-bis(diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane additive (0.0131 g) were added at room temperature. The mixture was stirred at 80C for 3 hours. After the temperature of the reaction mixture had returned to room temperature, the reaction mixture was diluted with ethyl acetate and insoluble matter was filtered off. The filtrate was poured into water and extracted with ethyl acetate. The organic layer was washed with water and saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure and the resultant residue was purified by silica gel column chromatography [elution solvent: n-hexane/ethyl acetate = 1/1-0/1 (V/V)] to obtain the title compound (27 mg (yield: 42%)) as a white solid.

Reference： [1]Patent: EP3438103,2019,A1 .Location in patent: Paragraph 0152; 0153

88
[ 1020174-04-2 ]
4-{8-amino-5-chloroimidazo[1,2-a]pyrazin-6-yl}benzonitrile [ No CAS ]
4-[8-amino-6-(1-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyrazin-5-yl]-2-chlorophenol hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 130℃; for 30h;Inert atmosphere;	General procedure: In a pressure tube were mixed 4-{8-amino-5-chloroimidazo[1 ,2-a]pyrazi n-6-yl}benzonitrile (145 mg, 0.54 mmol), 3-chloro-4-hydroxyphenylboronic acid (139 mg, 0.81 mmol, 1.5 equiv.) andNa2003 (114 mg, 1.08 mmol, 2 equiv.) in a 10:1 mixture of 1,4-dioxane:water(6 mL). The reaction mixture was sparged with argon for 10 mi Pd(PPh3)4 (31 mg, 0.03 mmol, 5 mol%) was then added and the tube was capped and the reaction mixture was warmed to 130O and stirred for 3h. After that time, the reaction mixture was then cooled down to r.t., diluted with water and separated aqueous layer was extracted with DOM (3x1 0 mL), EtOAc (2x 10 mL) thenwith 3:1 0H013:i-PrOH mixture (lx 10 mL). Oombined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the crude material as a brown residue. The obtained crude material was purified by flash chromatography on silica eluting with DOM:MeOH (10:0 - 9:1). Additional purification by HPLO led to the title product (20 mg, 0.055 mmol, 10%) as a white solid. ESl-MS: 362.5 [M+H]+. 1 H NMR (300MHz, DMSO-d6)67.72 (d, J = 8.0 Hz, 2H), 7.54 (s, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.41 (s, 1H), 7.36 (s, 1H), 7.13 (d, J = 9.4 Hz, 3H), 7.04 (d, J = 8.3 Hz, 1 H).

Reference： [1]Patent: WO2019/2606,2019,A1 .Location in patent: Page/Page column 93; 95; 104

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	1020174-04-2	MDL No. :	MFCD04114000
Formula :	C₁₀H₁₇BN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BJMSXWLXFYZHIU-UHFFFAOYSA-N
M.W :	208.07	Pubchem ID :	2760077
Synonyms :

Num. heavy atoms :	15
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.7
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	59.96
TPSA :	36.28 Å²

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) :	-6.68 cm/s

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

[ CAS No. 1020174-04-2 ] {[proInfo.proName]}

Quality Control of [ 1020174-04-2 ]

Related Doc. of [ 1020174-04-2 ]

Product Details of [ 1020174-04-2 ]

Calculated chemistry of [ 1020174-04-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1020174-04-2 ]

Application In Synthesis of [ 1020174-04-2 ]

[ 1020174-04-2 ] Synthesis Path-Upstream 1~6

[ 1020174-04-2 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 1020174-04-2 ]

Organoboron

Related Parent Nucleus of
[ 1020174-04-2 ]

Pyrazoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.25
Log Po/w (WLOGP) :	0.72
Log Po/w (MLOGP) :	0.3
Log Po/w (SILICOS-IT) :	0.29
Consensus Log Po/w :	0.51

Log S (ESOL) :	-2.1
Solubility :	1.66 mg/ml ; 0.00798 mol/l
Class :	Soluble
Log S (Ali) :	-1.61
Solubility :	5.1 mg/ml ; 0.0245 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.4
Solubility :	0.823 mg/ml ; 0.00395 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.05

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

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P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
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P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
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P401
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