Name: 628692-15-9|(2-Methoxypyrimidin-5-yl)boronic acid|98%
Brand: Ambeed
SKU: A110597
Price: 9.0 USD
Availability: InStock
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1
[ 954123-48-9 ]
[ 628692-15-9 ]
2-methoxy-5-(3-(((4-phenylpiperidin-4-yl)methoxy)methyl)-5-(trifluoromethyl)phenyl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 1 2-Methoxy-5-(3-(((4-phenylpiperidin-4-yl)methoxy)methyl)-5-(trifluoromethyl)phenyl)pyrimidine. tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-phenylpiperidine-1-carboxylate (60. 0 mg, 0.11 mmol), 2-methoxy-5-pyridine boronic acid (72.0 mg, 0.47 mmol), and tetrakis(triphenylphosphine) palladium(0) (17.1 mg, 0.011 mmol) were combined in dry tetrahydrofuran (2 mL) in a microwave tube and sealed. The mixture was flushed with nitrogen then 0.35 mL of a 1 N potassium hydroxide aqueous solution was introduced. The mixture was heated at 120° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated and treated with a trifluoroacetic acid/methylene chloride mixture (1:1, 2 mL) for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. Concentration and preparative HPLC afforded 21.0 mg (42percent) of the desired compound as its TFA salt. 1H-NMR (CDCl3, 500 MHz) delta 8.57 (s, 2H), 7.54 (s, 1H), 7.25-7.31 (m, 8H), 4.40 (s, 2H), 4.03 (s, 3H), 3.40 (s, 2H), 2.83-2.88 (m, 2H), 2.64-2.69 (m, 2H), 2.10-2.18 (m, 2H), 1.77-1.86 (m, 2H). Mass spec.: 458.18 (MH)+.

Reference： [1]Patent: US2007/249607,2007,A1 .Location in patent: Page/Page column 94-95

2
[ 958852-14-7 ]
[ 628692-15-9 ]
[ 958852-15-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 8h;	A mixture of 6-(methyloxy)-3-pyridinyl]boronic acid (225 mg, 1.5 mmol), 4- iodo-6-quinolinecarbaldehyde (283 mg, 1 mmol), tetrakistriphenylphosphine palladium (0) (57 mg, 0.05 mmol), 2 M aqueous K2CO3 (2.5 ml. of a 2 M solution), and dioxane (5 ml.) ) was heated at 100 0C for 8 h and cooled to room temperature. The dioxane was removed under reduced pressure and the residue dissolved in 2:1 mixture of methylene chloride/water and the solution filtered. The organic layer was separated and dried with sodium sulfate and the crude product obtained by decanting the solution and evaporation of the methylene chloride. The crude product was purified by silica gel chromatography eluting with methylene chloride/methanol (0-1percent methanol gradient) to give the title compound (250 mg, 95 percent). MS(ES)+ m/e 265 [M+H]+.

Reference： [1]Patent: WO2007/136940,2007,A2 .Location in patent: Page/Page column 43

3
[ 628692-15-9 ]
3-(4-aminophenyl)-7-(2-methoxy-5-pyrimidinyl)thieno[3,2-c]pyridin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 133A 3-(4-aminophenyl)-7-(2-methoxy-5-pyrimidinyl)thieno[3,2-c]pyridin-4-amine The desired product was prepared by substituting 2-methoxy-5-pyrimidinylboronic acid for 4-pyridylboronic acid in Examples 121A-B. MS (ESI(+)) m/e 350 (M+H)+.

Reference： [1]Patent: US2005/43347,2005,A1 .Location in patent: Page/Page column 44

4
[ 84249-14-9 ]
[ 628692-15-9 ]
C₁₀H₁₀N₄O [ No CAS ]

Reference： [1]Patent: WO2005/89763,2005,A1 .Location in patent: Page/Page column 24

5
[ 867256-58-4 ]
[ 628692-15-9 ]
[4-(2-methoxy-pyrimidin-5-yl)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 48h;Heating / reflux;	To a stirred solution of (4-bromo-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl- pyrrolidin-l-yl)-methanone (100mg, 0.297mmol), sodium carbonate (94.4mg, 0.890mmol) and 2-Methoxy-5-pyrimidine boronic acid (230mg, 1.48mmol) in toluene (5ml), water (Iml) and ethanol (1.5ml) under nitrogen was added Tetrakis (triphenylphosphine) palladium (0) (34.3mg, 0.030mmol). The reaction was then heated to reflux for 48h. The reaction was allowed to cool and bound to a SCX-2 cartridge (5g). The cartridge was washed with two cartridge volumes of dimethylformamide and one volume of methanol. The product was eluted using 2M ammonia in methanol. The ammonia/methanol solution was evaporated on a Genevac HT4. The sample was further purified by prep-LCMS. The resulting acetonitrile/water fractions were combined and evaporated using a Genevac to give 51mg of a colourless oil (47percent). MS (ES+) 367.3
47%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 48h;Reflux; Inert atmosphere;	Example 55[4-(2-Methoxy-pyrimidin-5-yl)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone Procedure SS: To a stirred solution of (4-bromo-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone (100 mg, 0.297 mmol), sodium carbonate (94.4 mg, 0.890 mmol) and 2-Methoxy-5-pyrimidine boronic acid (230 mg, 1.48 mmol) in toluene (5 ml), water (1 ml) and ethanol (1.5 ml) under nitrogen was added Tetrakis (triphenylphosphine) palladium (0) (34.3 mg, 0.030 mmol). The reaction was then heated to reflux for 48 h. The reaction was allowed to cool and bound to a SCX-2 cartridge (5 g). The cartridge was washed with two cartridge volumes of dimethylformamide and one volume of methanol. The product was eluted using 2M ammonia in methanol. The ammonia/methanol solution was evaporated on a Genevac HT4. The sample was further purified by prep-LCMS. The resulting acetonitrile/water fractions were combined and evaporated using a Genevac to give 51 mg of a colourless oil (47percent). MS (ES+) 367.3

Reference： [1]Patent: WO2005/97740,2005,A1 .Location in patent: Page/Page column 67-68
[2]Patent: US2010/48580,2010,A1 .Location in patent: Page/Page column 28

6
[ 880770-31-0 ]
[ 628692-15-9 ]
8-[3-(2-methoxy-pyrimidin-5-yl)-pyrrolo[2,3-b]pyridine-1-sulfonyl]-quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 120℃; for 0.166667h;Microwave irradiation;	Step-2 Preparation of 8-[3-(2-methoxy-pyrimidin-5-yl)-pyrrolo[2,3-b]pyridine-1-sulfonyl]-quinoline 43 In a microwave reaction tube, 8-(3-bromo-pyrrolo[2,3-b]pyridine-1-sulfonyl)-quinoline (44, 68 mg, 0.18 mmol), 2-methoxy-pyrimidine-4-boronic acid (67.4 mg, 0.438 mmol), and tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.0088 mmol) were mixed in 1.0 M of potassium carbonate (0.52 mL) and tetrahydrofuran (0.84 mL). The resulting mixture was heated at 120° C. in a CEM Discover microwave unit for 10 minutes. Ethyl acetate and water were added and two layers were separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over sodium sulfate. The product was concentrated under reduced pressure and the resultant crude material was purified by column chromatography (80-90percent ethyl acetate in hexane) to yield the desired product as a white solid (43, 0.005 g, 0.01 mmol). MS(ESI) [M+H+]+=417.8.

Reference： [1]Patent: US2006/100218,2006,A1 .Location in patent: Page/Page column 63

7
[ 873663-39-9 ]
[ 628692-15-9 ]
2-(3-acetamidophenyl)-4-(2-methoxypyrimidin-5-yl)-6-morpholinopyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 60℃; for 36h;	A mixture of 2-(3-acetamidophenyl)-4-bromo-6-morpholinopyrimidine (0.037 g),<strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (0.019 g), tetrakis(triphenylphosphine)palladium(0)(3 mg), a saturated aqueous sodium bicarbonate solution (0.2 ml) and 1,2-dimethoxyethane(2 ml) was stirred and heated to 60°C for 18 hours under an atmosphere of nitrogen. A secondportion of each of <strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (0.019 g),tetrakis(triphenylphosphine)palladium(0) (2 mg), a saturated aqueous sodium bicarbonatesolution (0.2 ml) and 1,2-dimethoxyethane (1 ml) was added and the resultant mixture washeated to 60°C for a further 18 hours. The resultant reaction mixture was evaporated and theresidue was triturated under a 5:1 mixture (1 ml) of methylene chloride and methanol. Thesoluble material was purified by column chromatography on reversed-phase silica using an'Isolute SCX' column (1 g; International Sorbent Technology Limited, Mid Glamorgan, UK)by initially washing the column with methanol (5 ml) followed by elution with a 5:3:2 mixture of methanol, methylene chloride and a 7M methanolic ammonia solution. The material soobtained was dried under vacuum. There was thus obtained the title compound as a solid(0.034 g); NMR Spectrum: (DMSOd6) 2.05 (s, 3H), 3.66-3.8 (m, 8H), 3.97 (s, 3H), 7.3-7.37(m, 2H), 7.82 (d, 1H), 8.03-8.09 (m, 1H), 8.52 (s, 1H), 9.38 (s, 2H), 9.98 (s, 1H); MassSpectrum: M+HM07.

Reference： [1]Patent: WO2006/5915,2006,A1 .Location in patent: Page/Page column 83; 84

8
[ 212267-75-9 ]
[ 628692-15-9 ]
N-[(2,6-dimethylphenyl)methyl]-2,3-dimethyl-6-[2-(methyloxy)-5-pyrimidinyl]imidazo[1,2-a]pyridin-8-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 100℃; for 2h;Microwave irradiation;	Example 75;. iV-[(2,6-Dimethylphenyl)methyI]-2,3-dimethyl-6-[2-(methyIoxy)-5- pyrimidinyl] imidazo [1 ,2-a] pyridin-8-amine EPO <DP n="86"/>A mixture of 6-bromo-iV-[(2,6-dimethylphenyl)methyl]-2,3-dimethylimidazo[l ,2- alpha]rhoyridin-8-amine (500 mg, 1.39 mmol; WO 98/37080) and 2-methoxvpyrimidine-5- boronic acid (430 mg, 2.79 mmol) in 2M aqueous sodium carbonate (3 niL) and dimethylformamide (6 mL) was degassed with argon and then treated with [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium (10 mg, 0.01 mmol). The mixture was heated in an Initiator.(TM). Microwave Synthesizer at 100°C for 2 hours. The resulting reaction mixture was applied to an Isolute.(R). SCX cartridge. Elution with methanol, then 2M and 7M NH3 in methanol gave, after evaporation, the crude product which was further purified by silica gel chromatography eluting with ethyl acetate/hexane mixtures to yield the title compound. MS (ES+ve): [M+H]+ at m/z 388 (C23H25N5O requires [M+H]+ at m/z 388).

Reference： [1]Patent: WO2006/100119,2006,A1 .Location in patent: Page/Page column 84-85

9
1-[3-(4-bromo-phenyl)-trans-cyclobutyl]-(2R)-2-methyl-pyrrolidine [ No CAS ]
[ 628692-15-9 ]
2-methoxy-5-{4-[3-({2R}-2-methyl-pyrrolidin-1-yl)-trans-cyclobutyl]-phenyl}-pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In isopropyl alcohol; at 90℃; for 5h;	Example 16C; 2-Methoxy-5-{4-[3-({2R}-2-methyl-pyrrolidin-1-yl)-trans-cyclobutyl]-phenyl}-pyrimidine; To a solution of the product from Example 16B (50 mg, 0.17 mmol) in isopropyl alcohol (4 mL) under an atmosphere of nitrogen was added 2-methoxypyrimidine-5-boronic acid (Frontier Scientific, Inc., Logan, Utah, USA) (30 mg, 0.2 mmol), dichlorobis(triphenylphosphine)palladium(II) (6 mg, 8.5 mumol), and potassium carbonate (59 mg, 0.43 mmol). The mixture was heated at 90° C. for 5 hrs, cooled to ambient temperature and partitioned between ethyl acetate (25 mL) and H2O (10 mL). The organic extraction was washed with brine, dried (MgSO4), filtered, concentrated, and chromatographed on silica gel eluting with 3percent (9:1 MeOH:concentrated NH4OH) in dichloromethane to provide 41 mg of the title compound. 1H NMR (300 MHz, CD3OD) delta 1.13 (d, J=6 Hz, 3H), 1.47 (m, 1H), 1.77 (m, 2H), 1.99 (m, 1H), 2.27 (m, 1H), 2.41 (m, 2H), 2.62 (m, 3H), 3.05 (m, 1H), 3.38 (m, 1H), 3.55 (m, 1H), 4.05 (s, 3H), 7.46 (d, J=9 Hz, 2H), 7.59 (d, J=9 Hz, 2H), 8.81 (s, 2H); (DCl/NH3) m/z 324 (M+H)+.

Reference： [1]Patent: US2007/78133,2007,A1 .Location in patent: Page/Page column 28-29

10
[ 944058-81-5 ]
[ 628692-15-9 ]
2-(2-methoxypyrimidin-5-yl)-4-(methylsulfonylmethyl)-6-morpholin-4-yl-pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(I) thiophene-2-carboxylate; zinc diacetate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 130℃; for 0.75h;Microwave irradiation;	The compounds shown in table 1 were prepared in an analogous manner to 4- (methylsulfonylmethyl)-6-morpholin-4-yl-2-thiophen-3-yl-pyrimidine (example 1), except where noted. Table 1Example 10: H NMR (300.132 MHz, DMSO) 53.19 (s, 3H), 3.72 (s, 8H), 4.01 (s, 3H),4.50 (s, 2H), 6.94 (s, IH), 9.38 (s, 2H) iPurification/Analysis details for examples 1 to 12:Dissolution Solvent 4 ml DMFInstrument Waters XBridge Prep, Cl 8 5 mum 100 x 19 mmColumn Phenomenex Gemini 5mu, Cl 8 100 x 21.2 mmFraction Trigger uv (at) 254 nmGradient 0 - 1 min 30percent MeCN, 9.5 min 60percent MeCNSolvent A WaterSolvent B AcetonitrileSolvent C - Modifier 5percent 4:3:3 880 Ammonia: Acetonitrile: WaterFlow Rate 20 ml/minAt Column Dilution Solvent AcetonitrileAt Column Dilution Flow Rate 1.0 ml/minTransfer solvent 1 ml DMF per tube + MeOH washLCMS 50 mul made upto 1 ml with MeCNAnalytical LCMS Method Phenomenex Gemini 5mu, C18 50 x 2 mm, 1.2 ml/min0 min 95:0:5 A:B:C, 4 min 0:95:5 A:B:CA MeCN, B H2O, C 1:1 MeCN:H2O 1percent Ammonia acid

Reference： [1]Patent: WO2007/80382,2007,A1 .Location in patent: Page/Page column 101-102

11
[ 39263-32-6 ]
[ 628692-15-9 ]
[ 944279-14-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 100℃; for 12h;	A mixture of Intermediate 3 (602 mg), 2-methoxypyrimidme-5-boronic acid(Frontier, 1.5 eq, 706 mg), and tetrakis(triphenylphosphine)palladium (0) (352 mg) was heated in DME / 2N sodium carbonate (aq, 2:1, 20 ml) at 100 ° for 12 h. Aqueous workup between water and EtOAc gave a brown solid that purified by SPE (Si, 20 g) by elution with DCM (4x10 ml) then EtOAc (4x10 ml), to give a solid that was triturated with DCM / petrol, and filtered to give a light brown solid (660 mg).1H NMR delta 8.85 (2H, s), 7.8 (IH, s), 7.6 (>3H, m), 6.88 (IH, d, J 8.85Hz), 6.3 (2H, s), 3.93 (3H, s); LC-MS rt 2.39 m/z 226 ES-.

Reference： [1]Patent: WO2007/80401,2007,A1 .Location in patent: Page/Page column 45

12
[ 950738-61-1 ]
[ 628692-15-9 ]
[ 950737-16-3 ]

Yield	Reaction Conditions	Operation in experiment
10%	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; water; at 100℃; for 0.277778h;microwave irradiation;	To a solution of N-[3-(3-bromo-pyrazolo[1,5-a]pyrimidin-7-yl)-phenyl]-3-trifluoromethyl-benzamide, (100 mg, 0.216 mmol) in ethylene glycol dimethyl ether (3 mL) was added 2-methoxypyrimidine-5-boronic acid (66 mg, 0.433 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (35 mg, 0.043 mmol), sodium carbonate (2M aqueous solution, 0.43 mL, 0.864 mmol). After microwaving at 100° C. for 1000 seconds, the solution was diluted with ethyl acetate, filtered with celite, concentrated, and purified by HPLC (10 mg, 10percent yield). MS 489.2 [M-H]

Reference： [1]Patent: US2007/219186,2007,A1 .Location in patent: Page/Page column 48-49

13
[ 756503-69-2 ]
[ 628692-15-9 ]
[ 1023327-92-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; ethanol; water; at 100℃; for 0.166667h;Microwave irradiation;	Intermediate 11: Cvclopentyl 5-r(5-(6-amino-5-ri-(2,6-dichloro-3-fluoro phenyl) ethoxv1pvridin-3-vl>pvrimidin-2-vl)oxv1-/V-(ferf-butoxvcarbonvpi-L-norvalinateThe title intermediate was prepared by the method outlined in Scheme 12.Stage 1Scheme 12Stage 1- 3-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-(2-methoxypyrimidin-5-yl) pyridin-2-amineA solution of Intermediate 7 (224 mg, 0.591 mmol), <strong>[628692-15-9](2-methoxypyrimidin-5-yl)boronic acid</strong> (100 mg, 0.650 mmol) and PdCI2(dppf) (48.2 mg, 0.059 mmol) was made up in DME/EtOH (1 ml_). To this was added sodium carbonate (68.9 mg, 0.650 mmol) (0.69 mL of a 1 M solution) and the solution was subjected to microwave irradiation for 10 min at 100 0C. The dark mixture was poured onto water and extracted with EtOAc (5 mL). The combined organic phases were washed with water and brine (2 x 3 mL each), dried EPO <DP n="40"/>(MgSO4) and evaporated. The residue was subjected to column chromatography (40 g) eluting with 40percent EtOAc in hexanes to give the desired material (100 mg) as a colourless solid. ESMS: m/z 409 and 411 (M+H)+

Reference： [1]Patent: WO2008/53157,2008,A1 .Location in patent: Page/Page column 38-39

14
[ 1034131-30-0 ]
[ 628692-15-9 ]
[ 1034131-34-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium fluoride;tris-(dibenzylideneacetone)dipalladium(0); tri tert-butylphosphoniumtetrafluoroborate; In tetrahydrofuran; at 60℃; for 4h;	Example 64; [0203] (a) terf-Butyl 2-(4-hydroxy-6-(2-methoxypyrimidin-5-yl)-l- methyl-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamido)acetate. A mixture of 2-methoxypyrimidine-5-boronic acid (0.34 g, 2.2 mmol), tert-butyl 2- (4-hydroxy-6-iodo- 1 -methyl-2-oxo- 1 ,2-dihydro- 1 , 8-naphthyridine-3 - carboxamido)acetate (0.500 g, 1.1 mmol, Example 26 (g)), t-tert- butylphosphonium tetrafluoroborate (0.063 g, 0.22 mmol), Pd2(dba)3 (0.100 g, 0.11 mmol) and potassium fluoride (0.076 mg, 3.3 mmol) in THF (8 mL) was stirred at 60°C for 4 hours under an argon atmosphere. The reaction mixture was left to reach room temperature and was filtered. The filter cake was washed with EtOAc (3x100 mL). The combined filtrate was evaporated under reduced pressure, and the residue was diluted with DCM (100 mL), and was filtered. The filtrate was washed with deionized water (3x75 mL) and brine (75 mL), dried over MgSOphi and filtered. The filtrate was evaporated under reduced pressure, and the <n="73"/>residue was purified by silica gel column chromatography (gradient: 0-33percent EtOAc/hexanes) to give the title compound.

Reference： [1]Patent: WO2008/76425,2008,A1 .Location in patent: Page/Page column 70-71

15
(trans)-8-(5-bromo-1H-benzimidazol-2-yl)-3-(2-fluorophenyl)-1-oxa-3-azaspiro[4.5]decan-2-one [ No CAS ]
[ 628692-15-9 ]
(trans)-3-(2-fluorophenyl)-8-(1H-benzimidazol-2-yl)-1-oxa-3-azaspiro[4.5]decan-2-one hydrochloride [ No CAS ]
(trans)-3-(2-fluorophenyl)-8-{5-[2-(methyloxy)-5-pyrimidinyl]-1H-benzimidazol-2-yl}-1-oxa-3-azaspiro[4.5]decan-2-one hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18.91%; 14.11%		Examples 57 and 58: (Trans)-3-(2-fluorophenyl)-8-{5-[2-(methyloxy)-5-pyrimidinyl1-1 H- benzimidazol-2-yl)-1-oxa-3-azaspiro[4.51decan-2-one (Example 57) and (trans)-8-(1 H- benzimidazol-2-yl)-3-(2-fluorophenyl)-1-oxa-3-azaspiro[4.51decan-2-one (Example 58); Example 57 Example 58To 8-(5-bromo-1 H-benzimidazol-2-yl)-3-(2-fluorophenyl)-1 -oxa-3-azaspiro[4.5]decan-2- one (Example 55, 50 mg, 0.113 mmol) dissolved in 1 ,4-dioxane (5 ml), Pd2dba3 (3.09 mg, 3.38 mumol), P(t-Bu)3 (22.77 mg, 0.1 13 mmol), [2-(methyloxy)-5-pyrimidinyl]boronic acid (26.0 mg, 0.169 mmol) and cesium carbonate (44.0 mg, 0.135 mmol) were added and the solution was stirred at 90 0C for 2 hours. Then the mixture was irradiated for 15 min at 160 0C. Pd2dba3 (3.09 mg, 3.38 mumol), P(t-Bu)3 (22.77 mg, 0.113 mmol), [2-(methyloxy)-5- pyrimidinyl]boronic acid (26.0 mg, 0.169 mmol) and cesium carbonate (44.0 mg, 0.135 mmol) were added and the mixture was irradiated for further 15 min at 160 0C. The reaction was cooled to room temperature and the mixture partitioned between water (3 ml) and DCM (3X3 ml). The organic layer was eluted through a SCX SPE cartridge (DCM 100, 2 CV, MeOH, 3 CV, MeOH/1 M Ammonia in methanol 8/2, 3 CV). Purification by chromatography on Si SPE cartridge (DCM/MeOH 100percent to 9/1 ) afforded 3-(2- fluorophenyl)-8-{5-[2-(methyloxy)-5-pyrimidinyl]-1 H-benzimidazol-2-yl}-1-oxa-3- azaspiro[4.5]decan-2-one and (trans)-8-(1 H-benzimidazol-2-yl)-3-(2-fluorophenyl)-1-oxa- 3-azaspiro[4.5]decan-2-one which were treated with 1.0M HCI in Et2O (0.135 ml) to afford the title compounds 3-(2-fluorophenyl)-8-{5-[2-(methyloxy)-5-pyrimidinyl]-1 H- benzimidazol-2-yl}-1-oxa-3-azaspiro[4.5]decan-2-one hydrochloride (Example 57, 9 mg, 14.1 1 percent) and (trans)-8-(1 H-benzimidazol-2-yl)-3-(2-fluorophenyl)-1-oxa-3- azaspiro[4.5]decan-2-one hydrochloride (Example 58, 9 mg, 18.91percent).Example 57: 1 H-NMR (400 MHz, CDCI3): delta 8.76 (2H, s), 7.77-7.93 (1 H, m), 7.46-7.61 (2H, m), 7.32-7.46 (1 H, m), 7.12-7.28 (3H, m), 4.09 (3H, s), 3.88-3.91 (2H, m), 3.12 (1 H, br s), 2.28-2.42 (2H, m), 2.12-2.26 (2H, m), 1.90-2.10 (4H, m); UPLC-MS: 0.56 min, m\\z 474 [M+H]+.Example 58: 1 H-NMR (400 MHz, CDCI3): delta 7.54 (2H, td), 7.34 (2H, dd), 7.12-7.23 (4H, m), 3.86 (3H, s), 3.03 (1 H, br s), 2.25-2.38 (2H, m), 2.11-2.22 (3H, m), 1.90-2.06 (4H, m); UPLC-MS: 0.54 min, m\\z 366 [M+H]+.

Reference： [1]Patent: WO2008/129007,2008,A1 .Location in patent: Page/Page column 93

16
[ 107346-32-7 ]
[ 628692-15-9 ]
4-amino-8-(2-methoxy-pyrimidin-5-yl)-N-propyl-cinnoline-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%		EXAMPLE 7 4-amino-8-(2-methoxypyrimidin-5-yl)-N-propyl-cinnoline-3-carboxamide Using method A, 4-amino-8-bromo-N-propyl-cinnoline-3-carboxamide (100 mg, 0.324 mmol) and <strong>[628692-15-9](2-methoxypyrimidin-5-yl)boronic acid</strong> (104 mg, 0.68 mmol) were reacted to afford the title compound (84 mg, 77percent yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) delta 9.1-9.3 (m, 1.5H), 8.96 (s, 2H), 8.47 (dd, J=8.4, 1.0 Hz, 1H), 8.1-8.4 (bm, 0.5 H), 7.99 (dd, J=7.2, 1.0 Hz, 1H), 7.83 (dd, J=8.4, 7.2 Hz, 1H), 4.01 (s, 3H), 3.32 (apparent q, J=7.4 Hz, 2H), 1.60 (apparent sextet, J=7.2 Hz, 2H), 0.91 (t, J=7.4 Hz, 3H). MS APCI, m/z=339 (M+H) HPLC 1.75 min.

Reference： [1]Patent: US2008/318925,2008,A1

17
[ 628692-15-9 ]
[ 834888-64-1 ]
[ 1092367-90-2 ]

Yield	Reaction Conditions	Operation in experiment
		7V-(2-chloro-6-methylphenyl)-2-(2'-methoxy-2-methyl-4,5'-bipyrimidin-6- ylamino)thiazole-5-carboxamide32 A mixture of 2-(6-chloro-2-methylpyrimidin-4-ylamino)-7V-(2-chloro-6- methylphenyl)-N-(4-methoxybenzyl)thiazole-5-carboxamide (37 mg, 0.072 mmol), 2- methoxypyrimidin-5-boronic acid (15 mg, 0.097 mmol), Pd(PPh3)4 (24 mg, 0.021 mmol), sodium carbonate (24 mg, 0.23 mmol) in THF (3.0 mL) and water (0.30 mL) was microwave heated at 160 0C for 1 h. The solvent was removed and the residue was purified by silica gel chromatography. The product was dissolved in 50percent TFA in DCM (3 mL) and triflic acid (0.2 mL). The reaction mixture was stirred for 3 h at rt, diluted with EtOAc, washed with sat. sodium bicarbonate, brine, dried over sodium sulfate and the solvent was removed. The residue was purified by preparative HPLC (ACN/ 0.1 percent TFA in water) and lyophilized to yield the title compound as a fluffy solid.1H-NMR (400 MHz, d6-DMSO) delta 12.21 (br s, IH), 10.00 (s, IH), 9.18 (s, 2H), 8.32 (s, IH), 7.41 (dd, J = 1.6, 7.6 Hz, IH), 7.33-7.27 (m, 3H), 4.02 (s, 3H), 2.68 (s, 3H), 2.25 (s, 3H); MS (m/z): 468.2 [M+l]+.

Reference： [1]Patent: WO2008/150446,2008,A1 .Location in patent: Page/Page column 38

18
[ 628692-15-9 ]
potassium (2-methoxypyrimidin-5-yl)trifluoroborate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 973 - 980

19
[ 322691-38-3 ]
[ 628692-15-9 ]
[ 1070216-80-6 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 6571 - 6580

20
propane-1-sulfonic acid [3-(2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4-difluoro-phenyl]-amide [ No CAS ]
[ 628692-15-9 ]
propane-1-sulfonic acid {2,4-difluoro-3-[2-(2-methoxy-pyrimidin-5-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-phenyl}-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; acetonitrile; at 160℃; for 0.166667h;Microwave irradiation;	Example 5; Synthesis of propane-1-sulfonic acid {2,4-difluoro-3-[2-(2-methoxy-pyrimidin-5-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-phenyl}-amide P-0004; Propane-1-sulfonic acid {2,4-difluoro-3-[2-(2-methoxy-pyrimidin-5-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-phenyl}-amide P-0004 was prepared in one step from propane-1-sulfonic acid [3-(2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4-difluoro-phenyl]-amide P-0002 as shown in Scheme 3.; Step 1-Preparation of propane-1-sulfonic acid {2,4-difluoro-3-[2-(2-methoxy-pyrimidin-5-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-phenyl}-amide (P-0004); In a microwave tube, propane-1-sulfonic acid [3-(2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4-difluoro-phenyl]-amide (P-0002, 95.0 mg, 0.207 mmol) and 2-methoxypyrimidine-5-boronic acid (10, 38.0 mg, 0.247 mmol) were added, followed by 1.4 mL of acetonitrile and 0.70 mL of 1.00 M potassium carbonate in water. [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (7.6 mg, 0.010 mmol) was added to reaction mixture and the resulting mixture was heated at 160° C. in the microwave for a total of 10 minutes. The reaction solution was extracted with ethyl acetate and water, followed by saturated sodium chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered and the filtrate concentrated under vacuum. The crude material was purified by silica gel chromatography eluting with a gradient of 10 to 70percent ethyl acetate in hexanes. The resulting material was further purified by silica gel chromatography eluting with a gradient of 1 to 3percent methanol in dichloromethane, and fractions containing the desired compound were extracted with 10 mL each of ethyl acetate and 1 M sodium hydroxide. The aqueous layer was treated with 0.8 ml, of 6 N hydrochloric acid, then extracted with 2.x.10 mL of ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound as a white solid (P-0004, 32 mg). MS (ESI) [M+H+]+=489.3.

Reference： [1]Patent: US2009/306087,2009,A1 .Location in patent: Page/Page column 40-41

21
potassium (2-methoxypyrimidin-5-yl)trifluoroborate [ No CAS ]
[ 628692-15-9 ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 7364 - 7369

22
[ 1186112-31-1 ]
[ 628692-15-9 ]
[ 1186110-91-7 ]

Yield	Reaction Conditions	Operation in experiment
29.8%	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 110℃; for 1h;Inert atmosphere; Microwave irradiation;	Example 285 l-Ethyl-3-(5-(2-methoxypyrimidin-5-yl)-4-(4-phenylthiazol-2-yl)pyridin-2-yl)urea To a nitrogen-purged mixture of l-(5-bromo-4-(4-phenylthiazol-2-yl)pyridin-2-yl)-3- ethylurea (Intermediate 16, 125 mg, 0.31 mmol) in DME (3 mL) were added 2- methoxypyrimidin-5-ylboronic acid (57.3 mg, 0.37 mmol), sodium bicarbonate (52.1 mg, 0.62 mmol) and water (1 mL), followed by tetrakis(triphenylphosphine)palladium(0) (71.6 mg, 0.06 mmol). The resulting mixture was microwaved for 60 min at 110°C. The solvent was evaporated from the reaction mixture, and the crude mass was washed with ethyl acetate and purified on reverse phase preparative HPLC to yield pure l-ethyl-3-(5-(2- methoxypyrimidin-5-yl)-4-(4-phenylthiazol-2-yl)pyridin-2-yl)urea (40.0 mg, 29.8 percent) as white solid powder.MS (ES+): 432.8 for C22H20N6O2S1H NMR a(DMSO Do): l.l(t, 3H), 3.2(qn, 2H), 4.0 (s, 3H), 7.32-7.45 (m, 3H), 7.61 (t, IH), 7.78 (d, 2H), 8.24 (s, IH), 8.27 (s, IH), 8.30 (s, IH), 8.61 (s, 2H), 9.40 (s, IH)

Reference： [1]Patent: WO2009/106885,2009,A1 .Location in patent: Page/Page column 228

23
[ 1198319-43-5 ]
[ 628692-15-9 ]
[ 1198319-44-6 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 91℃; for 4h;Inert atmosphere;	Step 3 : 6-(2-Dimethylamino-ethoxy)-5-(2-methoxy-pyrimidin-5-yl)-pyridin-3-ylamine (Intermediatel3). To a stirred solution of 5-bromo-6- (2-(dimethylamino)ethoxy)pyridin-3-amine(800 mg, 3.08 mmol, Intermediated) in dimethoxy ethane (20 mL), 2-methoxypyrimidin- 5-ylboronic acid (710 mg, 4.61 mmol) was added to the reaction mixture, nitrogen was purged for 5-10 minutes to remove dissolved oxygen. To this PalladiumTetrakis (533 mg, 0.46 mmol) was added followed by addition of aq solution of sodium carbonate (652 mg, 6.15 mmol). The resulting reaction mixture was heated at 91 0C for 4 hrs. Solvent from the reaction mixture was evaporated in vacuo and and the crude product was purified by fish chromatography using 8percentMeOH/DCM as solvent system to give 6-(2- (dimethylamino)ethoxy)-5-(2-methoxypyrimidin-5-yl)pyridin-3-amine (400 mg, 45.0 percent). MS (ES+): 290 for C14Hi9N5O2

Reference： [1]Patent: WO2009/147431,2009,A1 .Location in patent: Page/Page column 65

24
[ 1152781-33-3 ]
[ 628692-15-9 ]
5-[1-(2-Chloro-3-fluoro-4-methoxyphenyl)-2-(ethoxymethyl)-3,3,3-trifluoro-2-hydroxypropyl]amino}-7-fluoro-1-(2-methoxypyrimidine-5-yl)-1H-quinolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine;copper diacetate; In dichloromethane; at 20℃; for 156h;	100 mg (0.2 mmol) 5-[1-(2-Chloro-3-fluoro-4-methoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(methoxymethyl)propyl]amino}-7-fluoro-1H-quinolin-2-one, 62.5 mg (0.41 mmol) 2-methoxypyrimidine-5-yl boronic acid and 37 mg (0.2 mmol) water free copper acetate were stirred in 8.6 ml dichloromethane and 330 mul pyridine for 60 hours at room temperature. Then additional 35 mg 2-methoxypyrimidine-5-yl boronic acid and 20 mg water free copper acetate were added. After 4 days the solvent was removed column chromatography on silica gel (ethyl acetate/methanol 0 to 10percent) and additional preparative thin layer chromatography on silica gel (hexane/acetone 1:1) yielded 9.4 mg of the title compound. 1H-NMR (CDCl3); delta=3.25 (d, 1H), 3.29 (s, 3H), 3.64 (d, 1H), 3.89 (s, 3H), 4.09 (s, 3H), 5.24 (d, 1H), 5.66 (dd, 1H), 5.90 (dd, 1H), 6.16 (d, 1H), 6.65 (d, 1H), 6.90 (dd, 1H), 7.27 (d, 1H), 7.86 (d, 1H), 8.37 (d, 1H), 8.44 (d, 1H).

Reference： [1]Patent: US2010/16338,2010,A1 .Location in patent: Page/Page column 14

25
[ 1186395-80-1 ]
[ 628692-15-9 ]
4-(cyclohexylmethyl)-6-(2-methoxypyrimidin-5-yl)-2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]pyrido[2,3-b]pyrazin-3(4H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 4088 - 4091

26
[ 1186395-86-7 ]
[ 628692-15-9 ]
6-(2-methoxypyrimidin-5-yl)-2-[(2-morpholin-4-ylethyl)amino]-4-(2-propoxyethyl)pyrido[2,3-b]pyrazin-3(4H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 4088 - 4091

27
[ 1152781-33-3 ]
[ 628692-15-9 ]
[ 1205685-03-5 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; copper diacetate; In dichloromethane; at 20℃; for 60h;	Example 5 5-[1-(2-Chloro-3-fluoro-4-methoxyphenyl)-2-(methoxymethyl)-3,3,3-trifluoro-2-hydroxypropyl]amino}-7-fluoro-1-(2-methoxypyrimidine-5-yl)-1H-quinolin-2-one 100 mg (0.2 mmol) 5-[1-(2-Chloro-3-fluoro-4-methoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(methoxymethyl)propyl]amino}-7-fluoro-1H-quinolin-2-one, 62.5 mg (0.41 mmol) 2-methoxypyrimidine-5-yl boronic acid and 37 mg (0.2 mmol) water free copper acetate were stirred in 8.6 ml dichloromethane and 330 mul pyridine for 60 hours at room temperature. Then additional 35 mg 2-methoxypyrimidine-5-yl boronic acid and 20 mg water free copper acetate were added. After 4 days the solvent was removed column chromatography on silica gel (ethyl acetate / methanol 0 to 10percent) and additional preparative thin layer chromatography on silica gel (hexane / acetone 1:1) yielded 9.4 mg of the title compound. 1H-NMR (CDCl3); delta = 3.25 (d, 1H), 3.29 (s, 3H), 3.64 (d, 1H), 3.89 (s, 3H), 4.09 (s, 3H), 5.24 (d, 1H), 5.66 (dd, 1H), 5.90 (dd, 1H), 6.16 (d, 1H), 6.65 (d, 1H), 6.90 (dd, 1H), 7.27 (d, 1H), 7.86 (d, 1H), 8.37 (d, 1H), 8.44 (d, 1H).

Reference： [1]Patent: EP2149558,2010,A1 .Location in patent: Page/Page column 23

28
[ 870521-18-9 ]
[ 628692-15-9 ]
C₂₆H₂₂F₃N₃O₆S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 77 - 105

29
[ 870637-75-5 ]
[ 628692-15-9 ]
C₂₆H₂₂F₃N₃O₇ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 77 - 105

30
[ 1208499-98-2 ]
[ 628692-15-9 ]
[ 1208500-54-2 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 1652 - 1658

31
(4s)-4-(5-bromothiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane N-borane complex [ No CAS ]
[ 628692-15-9 ]
(4s)-4-[5-(2-methoxypyrimidin-5-yl)-1,3-thiazol-2-yl]oxy}-1-azatricyclo[3.3.1.13,7]decane N-borane complex [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 65℃; for 18h;	To a solution of the product of Example 20A (80 mg, 0.243 mmol) in DMF (2.5 mL) was added <strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (70.4 mg, 0.457 mmol), bis(triphenylphosphine)-palladium(II) chloride (8.5 mg, 0.012 mmol) and cesium carbonate (206 mg, 0.632 mmol). The reaction mixture was stirred at 65 °C for 18 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (30 mL) and partitioned between ethyl acetate (2 x 30 mL) and water (30 mL). The organic layers were combined and washed with brine (200 mL), dried (sodium sulfate) and concentrated in vacuo The residue was purified by silica gel flash <n="161"/>chromatography to afford the N-borane complex, which was then processed as described in Method C. The resulting mixture in 3 N HCl was concentrated to dryness and stirred in 10:1 diethyl ether/MeOH The precipitate was filtered and dried under vacuum to afford the titled compound as hydrochloride salt: 1H NMR (500 MHz, methanol-D4) delta ppm 1.94 - 2.02 (m, 2 H), 2.22 (br s, 1 H), 2.28 - 2.38 (m, 2 H), 2,62 - 2.71 (m, 2 H), 3.59 (br s, 2 H), 3 62 - 3.79 (m, 4 H), 4.04 (s, 3 H), 5.43 (t, J=3.2 Hz, 1H), 7.51 (s, 1 H), 8.71 - 8.75 (m, 2 H).. MS (ESI) m/z - 345 (M+H)+. Anal. Calcd. for C17H20N4O2S- 1.3 HCl: C, 52.11; H, 5.48; N, 14.30; Found: C, 52.08; H, 5.52; N, 14.33.

Reference： [1]Patent: WO2008/58096,2008,A2 .Location in patent: Page/Page column 159-160

32
[ 1220416-67-0 ]
[ 628692-15-9 ]
[ 1220127-41-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; XPhos;tris-(dibenzylideneacetone)dipalladium(0); In water; acetonitrile; at 90℃; for 1h;	A suspension of 5-bromo-N2-(3-chloro-4-fluoro-phenyl)-//-(3-dimethylamino-propyl)- pyrimidine-2,4-diamine (Intermediate 26, 160 mg, 0.40 mmol), 2-methoxy-5-pyrimidineboronic acid (92 mg, 0.60 mmol), tris(dibenzylideneacetone)dipalladium(0) (36.3 mg, 0.04 mmol), 2- dicyclohexylphosphino-2',4',6'-triiso-propyl-l,r-biphenyl (56.7 mg, 0.12 mmol) and sodium carbonate (42.0 mg, 0.40 mmol) in acetonitrile/water (4ml: ImI) was degassed with bubbling nitrogen for 10 min. and then heated to 90 0C. After 1 h LC-MS indicated complete reaction, and the reaction mixture was diluted with ethyl acetate (50 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated. Flash chromatography (12g column, 0-6percent MeOH/CH2Cl2 with 0.75percent triethylamine) provided 125 mg of the desired product. MS: ES+ 432 for C20H23ClFN7O.IH NMR (300 MHz, DMSO-D6) delta ppm 1.58 - 1.75 (m, 2 H) 2.02 (s, 6 H) 2.27 (t, J=6.59 Hz, 2 H) 3.34 - 3.44 (m, 2 H) 3.95 (s, 3 H) 7.23 - 7.37 (m, 2 H) 7.55 - 7.67 (m, 1 H) 7.74 - 7.80 (m, 1 H) 8.25 (dd, J=6.78, 2.64 Hz, 1 H) 8.56 (s, 2 H) 9.42 (s, 1 H).

Reference： [1]Patent: WO2010/38081,2010,A2 .Location in patent: Page/Page column 289

33
[ 1254171-04-4 ]
[ 628692-15-9 ]
[ 1254168-10-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 150℃; for 0.166667h;Inert atmosphere; Microwave irradiation;	Synthessis of 2-(2-chloro-6-fluorophenyl)-5-(2-methoxypyrimidin-5-yl)- lH-imidazole-4-carbonitrile (EX-42) [000264] To a solution of <strong>[628692-15-9]2-methoxypyrimidin-5-yl-5-boronic acid</strong> (R-41) (0.13 mmol) in 1 : 1: 1.5 = toluene : ethanol : water solution (0.9 rnL) was added 5-bromo-2-(2-chloro-6- fluorophenyl)-lH-imidazole-4-carbonitrile (1-10) (0.083 mmol) and Na2CO3 (0.25 mmol). The reaction mixture was degassed for 5 minutes with nitrogen and Pd(PPh3)4 (0.083 mmol) was added. The reaction was heated in a microwave oven at 150 0C for 10 minutes. Upon cooling the reaction was partitioned with EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered and reduced to dryness. The crude product was purified by flash column chromatography (EtOAc : hexanes = 2 : 1) to afford 2-(2-chloro-6- fluorophenyl)-5-(2-methoxypyrimidin-5-yl)-lH-imidazole-4-carbonitrile (EX-42) as a glassy white solid. 1H NMR (400MEtaz, J6-DMSO) delta 9.02 (2, IH), 7.68 (m, IH), 7.58 (d, J = 8.0 Hz, IH), 7.50 (t, J = 8.0 Hz, IH), 4.02 (s, 3H). MS (m/z) (M+l)+: 330.5.

Reference： [1]Patent: WO2010/127152,2010,A2 .Location in patent: Page/Page column 100-101

34
[ 494773-35-2 ]
[ 628692-15-9 ]
[ 1253936-62-7 ]

Yield	Reaction Conditions	Operation in experiment
54%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 100℃; for 0.5h;Inert atmosphere;	4-(2-Bromophenyl)-piperazine-l-carboxylic acid, t-butyl ester (10 g, 29.30 mmol) and 2- methoxypyrimidine-5-boronic acid (5 g, 32.48 mmol) are dissolved in DMF (200 mL) under a stream of nitrogen. To this mixture is added a 2M aqueous solution of sodium carbonate (73.26 mL, 150 mmol) followed by bis(triphenylphosphine) palladium (II) chloride (2.06 g, 2.93 mmol). The resulting mixture is allowed to stir at 100 0C for 30 min. A precipitate forms. Water is added and the resulting mixture is filtered to provide a gray colored solid which is air dried. The solid is then re-dissolved in dichloromethane (20 mL) and loaded on a 34Og Biotage SNAP column and eluted with 35percent ethyl acetate in hexanes to provide 4-[2-(2-methoxy-pyrimidin-5-yl)-phenyl]-piperazine-l-carboxylic acid t-butyl ester (5.87 g, 54percent yield).

Reference： [1]Patent: WO2010/126811,2010,A1 .Location in patent: Page/Page column 135-136

35
[ 1253936-66-1 ]
[ 628692-15-9 ]
[ 1253936-83-2 ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 100℃; for 0.5h;microwave irradiation;	The above intermediate (150 mg, 0.32 mmol), 2-(methoxy) pyrimidine-5-boronic acid (70 mg. 0.38 mmol), bis(triphenylphosphine)palladium (II) chloride (23 mg, 0.032 mmol), aqueous Na2CO3 solution (2N, 803mul, l.betammol) and dimethylformamide (2mL) are added to a 2-5 mL microwave tube. The reaction is carried out in a microwave oven at 100 0C for 30 min. The mixture turns black. The reaction mixture is filtered and washed with a bit MeOH/water (1/0.ImL). The clear filtrate is purified through prep- HPLC. Removal of the solvent gives the title compound as a colorless foam (1 lOmg, 69percent).

Reference： [1]Patent: WO2010/126811,2010,A1 .Location in patent: Page/Page column 137; 139

36
[ 1254567-35-5 ]
[ 628692-15-9 ]
[ 1254567-36-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; acetonitrile; at 160℃; for 0.25h;Microwave irradiation;	In a microwave vial, (3-ammo-2,6-difluoro-phenyl)-(5-iodo-lH-pyrrolo[2,3-b]pypidin-3-yl)- methanone (19, 1 36 g, 3 41 mmol), 2-methoxy-pypimidme-5-boronic acid (20. 1 05 g, 6 81 mmol), and [l,r-bis(diphenylphosphmo)ferrocene]dichloropalladium(II) (0 25 g, 0 34 mmol) were mixed in 22 mL of 1 00 M potassium carbonate in water and 18 mL of acetonitrilc I he resulting mixture was heated at 160 UC in the microwave for 15 minutes The resulting mixture was filteied through a thin la\\er of celite, and the celite bed was washed witn a mixture of w ater and etiiyl acetate The two layers of the filtrate were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and the filtrate concentrated under vacuum The residue was purified by flash silica gel chromatography eluting with ethyl acetate and dichloromethane to provide the desired compound (21, 0 567 g). MS(HSl) [M+H"]+ = 382 1.

Reference： [1]Patent: WO2010/129567,2010,A1 .Location in patent: Page/Page column 71-72

37
[ 1031432-16-2 ]
[ 628692-15-9 ]
[ 1186110-91-7 ]

Yield	Reaction Conditions	Operation in experiment
29.8%	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 110℃; for 1h;Inert atmosphere; Microwave irradiation;	Example 285l-Ethyl-3-(5-(2-methoxypyrimidin-5-yl)-4-(4-phenylthiazol-2-yl)pyridin-2-yl)ureaTo a nitrogen-purged mixture of l-(5-bromo-4-(4-phenylthiazol-2-yl)pyridin-2-yl)-3- ethylurea (Intermediate 16, 125 mg, 0.31 mmol) in DME (3 mL) were added 2- methoxypyrimidin-5-ylboronic acid (57.3 mg, 0.37 mmol), sodium bicarbonate (52.1 mg, 0.62 mmol) and water (1 mL), followed by tetrakis(triphenylphosphine)palladium(0) (71.6 mg, 0.06 mmol). The resulting mixture was microwaved for 60 min at 110°C. The solvent was evaporated from the reaction mixture, and the crude mass was washed with ethyl acetate and purified on reverse phase preparative HPLC to yield pure l-ethyl-3-(5-(2- methoxypyrimidin-5-yl)-4-(4-phenylthiazol-2-yl)pyridin-2-yl)urea (40.0 mg, 29.8 percent) as white solid powder.MS (ES+): 432.8 for C22H20N6O2S1H NMR O(DMSO DO): l.l(t, 3H), 3.2(qn, 2H), 4.0 (s, 3H), 7.32-7.45 (m, 3H), 7.61 (t, IH), 7.78 (d, 2H), 8.24 (s, IH), 8.27 (s, IH), 8.30 (s, IH), 8.61 (s, 2H), 9.40 (s, IH)

Reference： [1]Patent: WO2011/24004,2011,A1 .Location in patent: Page/Page column 222

38
[ 1272353-93-1 ]
[ 628692-15-9 ]
[ 1272354-28-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 12h;Inert atmosphere;	To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4- amine (300 mg, 0.87 mmol) in DMF (20 mL) and 3/40 (2 mL) under nitrogen was added <strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (199 mg, 1.30 mmol) and potassium carbonate (239 mg, 1.73 mmol). The resulting mixture was degassed with nitrogen for 15 min and then tetrakis(triphenylphosphine)palladium (100 mg, 0.086 mmol) was added. Upon completion of addition, the reaction mixture was again degassed with nitrogen for 10 min. After this time, the reaction mixture was heated to 90 °C where it stirred for 12h. After this time, the reaction mixture was allowed to cool to room temperature and then quenched by the addition of water. The reaction mixture was extracted with ethyl acetate and the organic layer was washed successively with water and brine. The combined organic layers were dried over Na2S04, filtered and concentrated under reduced pressure. The resulting concentrate was purified by preparative HPLC to afford 2-(2-methoxypyrimidin-5-yl)-5-phenyl-N-(pyridin-2- ylmethyl)quinazolin-4-amine (205 mg) as an off-white solid. Preparative HPLC Conditions: Column: Sunfire C18 (250 x 19 mm), Mobile Phase A: 0.1percent TFA in H20, Mobile Phase B: CH3CN, Gradient: 0 to 40percent B over 35 min, 100percent B for 10 min., Flow Rate: 14 niL/min., Retention time: 28 min. XH NMR (400 MHz, DMSO- d6) delta (ppm): 9.50 (s, 2H), 8.27 (d, J= A J Hz, 1H), 7.92 (d, J= 3.6 Hz, 2H), 7.85-7.81 (t, J= 8.0 Hz, 1H), 7.60-7.52 (m, 5H), 7.42-7.38 (m, 2H), 7.34-7.31 (m, 1H), 4.83 (d, J= 4.2 Hz, 2H), 4.04 (s, 3H). LCMS Method O: retention time 1.45 min, [M+l] = 421.2. HPLC Method B: purity 98.7percent, retention time 5.53 min.

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 831 - 834
[2]Patent: WO2011/28741,2011,A1 .Location in patent: Page/Page column 238

39
[ 944401-95-0 ]
[ 628692-15-9 ]
[ 1262940-12-4 ]

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 34 - 38

40
[ 1304777-36-3 ]
[ 628692-15-9 ]
[ 1304777-39-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 2484 - 2488

41
[ 628692-15-9 ]
[ 1192814-37-1 ]

Reference： [1]Patent: WO2011/53292,2011,A1
[2]Patent: JP5714745,2015,B2

42
[ 5305-59-9 ]
[ 628692-15-9 ]
[ 1192814-36-0 ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 125℃; for 0.333333h;Microwave irradiation;	Step A: 2'-methoxy-4,5'-bipyrimidin-6-amine6-Chloropyrimidin-4-amine (0.35 g, 2.70 mmol), 2-methoxypyrimidin-5- ylboronic acid (0.520 g, 3.38 mmol), Na2C03 (0.859 g, 8.11 mmol) andbis(triphenylphosphine)palladium(II) chloride (0.038 g, 0.054 mmol) were suspended in a mixture of DME/EtOH/water. (15:2:3 mL). The mixture was heated in the microwave synthesizer at 125 °C for 20 min and concentrated. The residue was purified by silica gel chromatography (0-5 percent 9: 1 methanol: ammonium hydroxide- ethyl acetate) to afford 6-(pyridin-3-yl)pyrimidin-4-amine (0.28 g, 1.378 mmol, 51 percent yield) as an off-white solid. LCMS R.T. = 0.53; [M+H]+ = 204.11.
51%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 125℃; for 0.333333h;Microwave irradiation;	6-Chloropyrimidin-4-amine (0.35 g, 2.70 mmol),<strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (0.520 g, 3.38 mmol),Na2CO3 (0.859 g, 8.11 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.038 g, 0.054 mmol) were suspendedin a mixture of DME/EtOH/water. (15:2:3 mL). Themixture was heated in the microwave synthesizer at 125° C.for 20 min and concentrated. The residue was purified bysilica gel chromatography (0-5percent 9:1 methanol:ammoniumhydroxide-ethyl acetate) to afford 6-(pyridin-3-yl)pyrimidin4-amine (0.28 g, 1.378 mmol, 51percent yield) as an off-white solid.

Reference： [1]Patent: WO2011/53292,2011,A1 .Location in patent: Page/Page column 251
[2]Patent: JP5714745,2015,B2 .Location in patent: Paragraph 0449; 0450

43
[ 1300583-90-7 ]
[ 628692-15-9 ]
[ 1300585-25-4 ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; N,N-dimethyl-formamide; at 80℃; for 12.5h;Inert atmosphere;	Example 1122-(1-(4-amino-3-(2-methoxypyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-oneTo a solution of Example 57c (0.400 g, 0.758 mmoles) in DMF (4 ml), ethanol (2 ml) and water (2 ml), 2-methoxypyrimidine-5-boronic acid (0.233 g, 1.517 mmoles) and sodium carbonate (0.241 g, 2.27 mmoles) were added and the system is degassed for 30 min.Tetrakistriphenylphosphine Palladium (0.043 g, 0.037 mmoles) was added under nitrogen atmosphere and heated to 80° C.After 12 h, the reaction mixture was celite filtered, concentrated and extracted with ethyl acetate.The organic layer was dried over sodium sulphate and concentrated under reduced pressure.The crude product was purified by column chromatography with methanol:dichloromethane to afford the title compound as off-white solid (0.200 g, 51percent yield). MP: 224-227° C. 1H-NMR (delta ppm, DMSO-d6, 400 MHz): delta 8.72 (s, 2H), 8.09 (s, 1H), 8.04 (dd, J=7.9, 1.4 Hz, 1H), 7.84 (m, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.52 (t, J=7.8 Hz, 1H), 7.32 (m, 1H), 7.12-6.95 (m, 5H), 6.03 (q, J=7.1 Hz, 1H), 1.90 (d, J=7.0 Hz, 3H). Mass: 509.99 (M+).

Reference： [1]Patent: US2011/118257,2011,A1 .Location in patent: Page/Page column 123

44
[ 1283639-04-2 ]
[ 628692-15-9 ]
[ 1283639-85-9 ]

Reference： [1]ACS Combinatorial Science,2011,vol. 13,p. 265 - 271

45
[ 1334167-41-7 ]
[ 628692-15-9 ]
[ 1334166-05-0 ]

Yield	Reaction Conditions	Operation in experiment
60%		Tetrakis(triphenylphosphine)palladium (0) (362 mg, 0.31 mmol) was added to a stirred solution of intermediate 27 (3.1 g, 10.4 mmol) and commercially available 2- methoxypyrimidine-5-boronic acid (1.93 g, 12.5 mmol) in a mixture of 1,4-dioxane (30 ml) and a saturated solution of sodium carbonate (10 ml). The mixture was stirred at 150 °C for 15 min. in a sealed tube under nitrogen and under microwave irradiation and then diluted with water and extracted with DCM. The organic layer was separated, extracted with brine, dried (Na2S04), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 2/98). The desired fractions were collected and evaporated in vacuo to yield compound 32 (2.06 g, 60percent) as a white solid.
60%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 150℃; for 0.25h;Sealed tube; Microwave irradiation; Inert atmosphere;	Example B323-(2-Methoxy-pyrimidin-5-yl)-2-methyl-8-morpholin-4-yl-imidazo[1,2-a]pyrazineTetrakis(triphenylphosphine)palladium (0) (362 mg, 0.31 mmol) was added to a stirred solution of intermediate 27 (3.1 g, 10.4 mmol) and commercially available 2-methoxypyrimidine-5-boronic acid (1.93 g, 12.5 mmol) in a mixture of 1,4-dioxane (30 ml) and a saturated solution of sodium carbonate (10 ml).The mixture was stirred at 150° C. for 15 min. in a sealed tube under nitrogen and under microwave irradiation and then diluted with water and extracted with DCM.The organic layer was separated, extracted with brine, dried (Na2SO4), filtered and the solvents evaporated in vacuo.The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 2/98).The desired fractions were collected and evaporated in vacuo to yield compound 32 (2.06 g, 60percent) as a white solid.

Reference： [1]Patent: WO2011/110545,2011,A1 .Location in patent: Page/Page column 113
[2]Patent: US2012/329792,2012,A1 .Location in patent: Page/Page column 55-56

46
[ 1350643-73-0 ]
[ 628692-15-9 ]
[ 1350643-67-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; ruphos;palladium diacetate; In 1,4-dioxane; water; at 125℃; for 3h;Inert atmosphere; microwave heating;	Compound 76 was prepared from compound 2 in two steps: A 2mL thick-walled microwave- reaction tube with stir bar was charged with compound 2 (120 mg, 0.24 mmol, 1 eq.), 2-methoxypyrimidine-5-boronic acid (74 mg, 2 eq.), sodium carbonate (130 mg, 5 eq.), palladium diacetate (8 mg, 0.15 eq.) and RuPhos (34 mg, 0.30 eq.), then capped with a septum and purged three time with vacuum, refilling with dry argon. 1,4-Dioxane (1.6 mL) and water (0.4 mL) were added and the reaction subjected to microwave heating at 125 °C during 3h, at which time LC/MS showed complete consumption of the starting chloride. The reaction mixture was diluted with DCM, treated with silica gel (0.5 g) and concentrated, then purified by flash chromatography, eluting 15g silica gel (gradient 1-4percentmethanol/methylene chloride) to provide 140 mg of compound 75 as an off-white powder. ESI-MS m/z 575.36[M+H]+.

Reference： [1]Patent: WO2011/146882,2011,A1 .Location in patent: Page/Page column 140

47
[ 513-37-1 ]
[ 628692-15-9 ]
[ 1352124-40-3 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 203 - 205

48
[ 930-29-0 ]
[ 628692-15-9 ]
[ 1352124-39-0 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 203 - 205

49
[ 575501-45-0 ]
[ 628692-15-9 ]
[ 1352124-41-4 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 203 - 205

50
[ 1359973-18-4 ]
[ 628692-15-9 ]
3-cyclopentyl-2-(2-methoxypyrimidin-5-yl)-3H-imidazo[4,5-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 20 - 110℃; under 1500.15 Torr; for 0.65h;Inert atmosphere; Microwave irradiation;	General procedure: To a solution of 3-substituted-2-iodo imidazo[4,5-b] pyridine derivative (1 equiv) in dimethoxyethane/MeOH (4:1), was added (A-taphos)2PdCl2 (5molpercent). The solution was purged with nitrogen and stirred at room temperature for 0.15 h, at which time the boronic acid (1.8equiv), and cesium fluoride (2 equiv) were added. The reaction solution was purged again with nitrogen and then placed in the microwave and heated for 10 to 30 mts at 110 C. When TLC and LCMS showed full consumption of starting materials, the reaction mixture was diluted with ethyl acetate, separated the ethyl acetate layer, given water wash, brine wash and was dried over anhydrous sodium sulphate and concentrated to get the crude material. The crude product was directly purified by column chromatography (0-20percent hexane/EtOAc) to isolate the 3-substituted-2-aryl/heteroarylimidao[4,5-b] pyridine derivatives.

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 1036 - 1041

51
[ 589-87-7 ]
[ 628692-15-9 ]
[ 27956-15-6 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 1662 - 1670

52
[ 628692-15-9 ]
[ 1358778-94-5 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 1662 - 1670

53
[ 628692-15-9 ]
[ 1358778-95-6 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 1662 - 1670

54
[ 628692-15-9 ]
[ 1312477-65-8 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 1662 - 1670

55
[ 1374260-87-3 ]
[ 628692-15-9 ]
[ 1374263-50-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium carbonate; In water; N,N-dimethyl-formamide; at 160℃; for 1h;Microwave irradiation;	Step 1:Preparation of tert-butyl (1-{4-[2-(2-methoxypyrimidin-5-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamateA mixture of tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (50 mg, 0.090 mmol), (2-methoxy pyrimidin-5-yl)boronic acid (28 mg, 0.18 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6 mg, 0.09 mmol), and 2M Na2CO3 aq. (0.090 mL, 0.18 mmol) in DMF (2.5 mL) was treated with microwave (160° C. for 1 hour).The mixture was diluted with AcOEt, washed with water (*3), brine, dried over Na2SO4, then filtrated through Celite pad.The filtrate was concentrated and the residue was purified by preparative thin-layer chromatography (n-hexane/AcOEt=1:2) to afford the desired product (45 mg, 86percent) as a yellow solid. 1HNMR (CDCl3) 400 MHz delta: 8.70 (s, 2H), 8.12 (dd, J=7.4 Hz and 1.7 Hz, 1H), 8.02 (d, J=3.4 Hz, 1H), 7.40 (d, J=8.0 Hz, 2H), 7.33 (td, J=8.0 Hz and 1.7 Hz, 1H), 7.18-7.14 (m, 2H), 6.97-6.94 (m, 1H), 6.82-6.79 (m, 1H), 6.61 (dd, J=8.0 Hz and 5.2 Hz, 1H), 6.25 (s, 1H), 5.07 (br s, 1H), 4.01 (s, 3H), 2.57-2.38 (m, 4H), 2.19-2.12 (m, 1H), 1.94-1.86 (m, 1H), 1.39 (br s, 9H). LCMS: 588 [M+H].

Reference： [1]Patent: US2012/108574,2012,A1 .Location in patent: Page/Page column 128

56
[ 1380106-79-5 ]
[ 628692-15-9 ]
C₁₉H₂₀ClN₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 86℃; for 5h;	General procedure: A mixture of 3-(4-bromo-2-chloro-phenyl)-N-(tetrahydropyran-2-yloxy)-acrylamide (70 mg, 0.194 mmol), pyridine-3-boronic acid (35.8 mg, 0.291 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (14.2 mg, 0.019 mmol) and potassium carbonate (42.9 mg, 0.31 mmol) in 1,4-dioxane (1.5 mL) and water (0.5 mL) was heated at 86 °C for 5 h. After cooling down the reaction mixture was partitioned between water and ethyl acetate, the organic layer was dried over sodium sulfate, filtered, concentrated and purified by thin layer chromatography (1 mm) eluting with 40percent ethyl acetate/hexanes to give the product as a white solid. This intermediate was dissolved in dichloromethane (1 mL), 4 N hydrogen chloride in dioxane (1 mL) was added. The reaction mixture was stirred at room temperature for 4 h and the precipitates were filtered. The solid was dried under vacuum to give 39 mg (Yield 65percent, HPLC purity 100percent) product as a white solid.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3754 - 3757

57
[ 1380106-79-5 ]
[ 628692-15-9 ]
[ 1380106-68-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3754 - 3757

58
[ 1381891-01-5 ]
[ 628692-15-9 ]
[ 1381889-75-3 ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 403 - 414

59
[ 1072854-55-7 ]
[ 628692-15-9 ]
[ 1072855-04-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 5618 - 5624

60
[ 1404115-45-2 ]
[ 628692-15-9 ]
C₂₈H₂₉N₃O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 6108 - 6115

61
[ 1404115-46-3 ]
[ 628692-15-9 ]
C₂₈H₂₉N₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 6108 - 6115

62
[ 1404115-47-4 ]
[ 628692-15-9 ]
C₂₈H₂₉N₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 6108 - 6115

63
[ 1404115-48-5 ]
[ 628692-15-9 ]
C₂₈H₂₈FN₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 6108 - 6115

64
[ 1411980-65-8 ]
[ 628692-15-9 ]
[ 1411980-74-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; isopropyl alcohol; toluene; at 85℃; for 3h;	Example 123; 2-(2-(4-(2-methoxypyrimidin-5-yl)-1H-pyrazol-1-yl)ethyl)-7-(4-(trifluoromethoxy)phenyl)phthalazin-1(2H)-one (Compound III-34) A mixture of 2-(2-(4-bromo-1H-pyrazol-1-yl)ethyl)-7-(4-(trifluoromethoxy)phenyl)phthalazin-1(2H)-one (35 mg, 0.073 mmol), <strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (13 mg, 0.087 mmol), dppf(Pd)Cl2 (2.7 mg, 0.0037 mmol), potassium carbonate (20 mg, 0.015 mmol) in degassed toluene (1 mL), degassed water (0.5 mL) and degassed isopropanol (0.5 mL) was heated at 85° C. for 3 hours. The layers were separated, the organic layer was concentrated and the residue was purified by reverse phase HPLC to provide 2-(2-(4-(2-methoxypyrimidin-5-yl)-1H-pyrazol-1-yl)ethyl)-7-(4-(trifluoromethoxy)phenyl)phthalazin-1(2H)-one as a white powder. C25H19F3N6O3. 509.2 (M+1). 1H NMR (DMSO) delta 8.74 (s, 1H), 8.38-8.44 (m, 2H), 8.26 (dd, J=2.0, 8.0 Hz, 1H), 8.20 (s, 1H), 8.03 (d, J=8.4 Hz, 1H), 7.94 (d, J=8.8 Hz, 2H), 7.84 (s, 1H), 7.51 (d, J=8.4 Hz, 2H), 4.56 (s, 4H), 3.87 (s, 3H).

Reference： [1]Patent: US2012/289493,2012,A1 .Location in patent: Page/Page column 97

65
[ 1417541-06-0 ]
[ 628692-15-9 ]
[ 1417541-07-1 ]

Yield	Reaction Conditions	Operation in experiment
32%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; at 120℃; for 0.416667h;Inert atmosphere; Microwave irradiation;	To a degassed mixture of ethanol and water (4:1, 20 mL) was added <strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (0.67 g, 4.4 mmol), Na2CO3 (1.24 g, 11.7 mmol) and N-[2-(4-bromophenyl)ethyl]-4,14-dihydroxy-17-methyl-6-oxomorphinan-3-carboxamide (2) (1.5 g, 2.9 mmol). The reaction mixture was further degassed and then Pd(PPh3)4 (0.32 g, 0.3 mmol) added. The reaction mixture was heated in a microwave reactor at 120° C. for 25 min. and cooled. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with 1:1 brine/water (3.x.35 mL). The organic phase was dried over MgSO4, filtered and evaporated. The resulting residue was further purified on silica eluting with dichloromethane/methanol (9:1) to give 4,14-dihydroxy-N-{2-[4-(2-methoxypyrimidin-5-yl)phenyl]ethyl}-17-methyl-6-oxomorphinan-3-carboxamide (3) (0.50 g, 32percent) as a yellow foam.

Reference： [1]Patent: US2013/5755,2013,A1 .Location in patent: Page/Page column 23

66
[ 1420620-43-4 ]
[ 628692-15-9 ]
[ 1420620-46-7 ]

Yield	Reaction Conditions	Operation in experiment
97 mg	With bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); sodium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere;	A mixture of compound 1-96 (100 mg, 0.219 mmol, 1 equiv.), 2-Methoxypyrimidine-5-boronic acid (67.4 mg, 0.438 mmol, 2 equiv.), sodium carbonate (116 mg, 1.094 mmol, 5 equiv.), and Pd-AMPHOS catalyst (31.0 mg, 0.044 mmol, 0.2 equiv.) in 2.9 mL degassed 4: 1 dioxane-water was sparged with argon for 2 min. The mixture was sealed and heated at 100 °C for lh, cooled, diluted with 10 mL each of DCM and water. The organic layer was collected, the aqueous layer was extracted with DCM (3x10 mL), the combined DCM layers were washed with water (10 mL), brine (10 mL), dried over sodium sulfate and the solvents were removed in vacuo. The residue was purified on silica gel (12 g, ISCO) using 0-10percent methanol in 1 : 1 DCM-EtOAc as eluent to provide 97 mg of compound 1-97 as a light yellow solid. ESI-MS m/z: 531.3 [M+H]+.

Reference： [1]Patent: WO2013/12915,2013,A1 .Location in patent: Paragraph 00820

67
[ 1350643-72-9 ]
[ 628692-15-9 ]
[ 1420627-92-4 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In N,N-dimethyl acetamide; water; at 120℃; for 16h;Sealed tube;	0740] To a mixture of (S)-3-(1-aminoethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one 1 (1.41 g, 4.72 mmol) and <strong>[628692-15-9](2-methoxypyrimidin-5-yl)boronic acid</strong> (1.09 g, 7.08 mmol) in anhydrous DMA (20 mL) in a sealed tube, PdCl2(dppf) (309 mg, 0.38 mmol) and aqueous Na2CO3 solution (1 M, 14.2 mL, 14.2 mmol) were added and the resulting mixture was stirred at 120° C. for 16 h. The reaction mixture was allowed to cool to RT, quenched with water, and then extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was slurried in ether for 10 min. The solid was collected by filtration, rinsed with ether and dried in vacuo to afford a first amount of product 2. The filtrate was concentrated in vacuo and the residue was further purified by ISCO column chromatography using a silica gel cartridge and eluting with 0-8percent MeOH-DCM to afford a second amount of product 2.

Reference： [1]Patent: US2013/53362,2013,A1 .Location in patent: Paragraph 0740

68
[ 1431542-54-9 ]
[ 628692-15-9 ]
[ 1431542-10-7 ]

Yield	Reaction Conditions	Operation in experiment
43%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 140℃; for 0.166667h;Inert atmosphere; Microwave irradiation;	To a mixture of 2-methoxypyrimidin-5-yl boronic acid (36.9 mg, 0.240 mmol) and Pd(PPh3)4 (1 1 .56 mg, 0.010 mmol) was added a solution of 1 -{4-[4-(6-Bromo-quinazolin-4-yl)-pyridine- 2-carbonyl]-piperazin-1 -yl}-ethanone (88 mg, 0.200 mmol) in 2 mL of acetonitrile. The reaction mixture was flushed with argon and a 1 M aqueous solution of Na2C03 (0.400 mL, 0.400 mmol) was added and the vial capped. The reaction mixture was heated to 120°C for 10 min using a microwave oven then cooled down to rt, diluted with EtOAc, filtered through a Celite pad and concentrated. Purification by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HC03 MP gave the title compound (40 mg, 43percent yield) as a white powder. 1 H-NMR (400 MHz, DMSO-d6, 298 K): ? ppm 2.01 - 2.06 (d, 3 H) 3.48 (br.s., 3 H) 3.58 (br.s., 3 H) 3.65 (br.s., 1 H) 3.73 (br.s., 1 H) 3.99 (s, 3 H) 8.01 (dd, 1 H) 8.06 (br.s., 1 H) 8.28 (d, 1 H) 8.34 (d, 1 H) 8.49 (dd, 1 H) 8.87 (d, 1 H) 9.09 (s, 2 H) 9.47 (s, 1 H). MS: 470.6 [M+1 ]+, Rt(2) = 0.78 min.
43%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; acetonitrile; at 120℃; for 0.166667h;Inert atmosphere; Microwave irradiation;	To a mixture of 2-methoxypyrimidin-5-yl boronic acid (36.9 mg, 0.240 mmol) and Pd(PPh3), (11.56 mg, 0.010 mmol) was added a solution of 1 -{4-[4-(6-Bromo-quinazolin-4-yl)-pyridine- 2-carbonyl]-piperazin-1 -yl}-ethanone (88 mg, 0.200 mmol) in 2 ml_ of acetonitrile. The reaction mixture was flushed with argon and a 1 M aqueous solution of Na2CC>3 (0.400 mL, 0.400 mmol) was added and the vial capped. The reaction mixture was heated to 120°C for 10 min using a microwave oven then cooled down to rt, diluted with EtOAc, filtered through a Celite pad and concentrated. Purification by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HC03 MP gave the title compound (40 mg, 43percent yield) as a white powder. 1H-NMR (400 MHz, DMSO-d6, 298 K): delta ppm 2.01 - 2.06 (d, 3 H) 3.48 (br.s., 3 H) 3.53 (br.s., 3 H) 3.65 (br.s., 1 H) 3.73 (br.s., 1 H) 3.99 (s, 3 H) 8.01 (dd, 1 H) 8.06 (br.s., 1 H) 8.28 (d, 1 H) 8.34 (d, 1 H) 8.49 (dd, 1 H) 8.87 (d, 1 H) 9.09 (s, 2 H) 9.47 (s, 1 H). MS: 470.6 [Mi-1]+, Rt(2,) = 0.78 min.
43%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; acetonitrile; at 120℃; for 0.166667h;Inert atmosphere; Microwave irradiation;	Example 112' 1-(4-{4-[6-(2-Methoxy-pyrimidin-5-yl)-quinazolin-4-yl]-pyridine-2-carbonyl}-piperazin-1-yl)-ethanone To a mixture of 2-methoxypyrimidin-5-yl boronic acid (36.9 mg, 0.240 mmol) and Pd(PPh3)4 (11.56 mg, 0.010 mmol) was added a solution of 1-{4-[4-(6-Bromo-quinazolin-4-yl)-pyridine-2-carbonyl]-piperazin-1-yl}-ethanone (88 mg, 0.200 mmol) in 2 mL of acetonitrile. The reaction mixture was flushed with argon and a 1M aqueous solution of Na2CO3 (0.400 mL, 0.400 mmol) was added and the vial capped. The reaction mixture was heated to 120° C. for 10 min using a microwave oven then cooled down to rt, diluted with EtOAc, filtered through a Celite pad and concentrated. Purification by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HCO3 MP gave the title compound (40 mg, 43percent yield) as a white powder. 1H-NMR (400 MHz, DMSO-d6, 298 K): delta ppm 2.01-2.06 (d, 3H) 3.48 (br.s., 3H) 3.58 (br.s., 3H) 3.65 (br.s., 1H) 3.73 (br.s., 1H) 3.99 (s, 3H) 8.01 (dd, 1H) 8.06 (br.s., 1H) 8.28 (d, 1H) 8.34 (d, 1H) 8.49 (dd, 1H) 8.87 (d, 1H) 9.09 (s, 2H) 9.47 (s, 1H). MS: 470.6 [M+1]+, Rt(2')=0.78 min.

Reference： [1]Patent: WO2013/57711,2013,A1 .Location in patent: Page/Page column 134-135
[2]Patent: WO2013/88404,2013,A1 .Location in patent: Page/Page column 263; 264
[3]Patent: US2015/342951,2015,A1 .Location in patent: Paragraph 1075-1076

69
[ 1431542-30-1 ]
[ 628692-15-9 ]
{3-[7-(2-methoxy-pyrimidin-5-yl)-naphthalen-1-yl]-phenyl}-(4-methyl-piperazin-1-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 140℃; for 0.166667h;Inert atmosphere; Microwave irradiation;	To a mixture of [3-(6-Bromo-quinazolin-4-yl)-phenyl]-(4-methyl-piperazin-1 -yl)-methanone (50 mg, 0.122 mmol), 2-Methoxy-pyrimidine-5-boronic acid (22mg, 0.146 mmol) and Pd(PPh3)4 (7 mg, 0.006 mmol) was added 2 ml. of DME. The reaction mixture was flushed with argon and a 1 M aqueous solution of Na2C03 (0.243 ml_, 0.243 mmol) was added and the vial was capped. The reaction mixture was heated to 140°C for 10min using a microwave oven then cooled down to rt, diluted with CH2CI2, filtered through a Celite pad and portioned between H20/CH2CI2. The organic layer was washed with brine, dried over MgS04, filtered and evaporated. Purification by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HC03 MP gave the title compound (38 mg, 71 percent yield). 1H-NMR (400 MHz, DMSO-d6, 298 K): ? ppm 2.15 (s, 3 H) 2.20-2.38 (m, 4 H) 3.37-3.70 (m, 4 H) 3.99 (s, 3 H) 7.65 (d, 1 H) 7.73 (t, 1 H) 7.86 (s, 1 H) 8.02 (d, 1 H) 8.24 (d, 1 H) 8.33 (s, 1 H) 8.43 (d, 1 H) 9.05 (s, 2 H) 9.41 (s, 1 H) MS: 441.1 [M+1]+ , Rt (2)= 0.75min.
71%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 140℃; for 0.166667h;Microwave irradiation;	To a mixture of [3-(6-Bromo-quinazolin-4-yl)-phenyl]-(4-methyl-piperazin-1 -yl)-methanone (50 mg, 0.122 mmol), 2-Methoxy-pyrimidine-5-boronic acid (22mg, 0.146 mmol) and Pd(PPh3)4 (7 mg, 0.006 mmol) was added 2 mL of DME. The reaction mixture was flushed with argon and a 1 M aqueous solution of Na2C03 (0.243 mL, 0.243 mmol) was added and the vial was capped. The reaction mixture was heated to 140°C for 10min using a microwave oven then cooled down to rt, diluted with CH2CI2, filtered through a Celite pad and portioned between H2O/CH2CI2. The organic layer was washed with brine, dried over MgSC , filtered and evaporated. Purification by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HCO3 MP gave the title compound (38 mg, 71percent yield). 1H-NMR (400 MHz, DMSO-d6, 298 K): delta ppm 2.15 (s, 3 H) 2.20-2.38 (m, 4 H) 3.37-3.70 (m, 4 H) 3.99 (s, 3 H) 7.65 (d, 1 H) 7.73 (t, 1 H) 7.86 (s, 1 H) 8.02 (d, 1 H) 8.24 (d, 1 H) 8.33 (s, 1 H) 8.43 (d, 1 H) 9.05 (s, 2 H) 9.41 (s, 1 H) MS: 441.1 [M+1 ]+ , Rt (2,)= 0.75min.

Reference： [1]Patent: WO2013/57711,2013,A1 .Location in patent: Page/Page column 57-58
[2]Patent: WO2013/88404,2013,A1 .Location in patent: Page/Page column 186; 187

70
[ 1435972-38-5 ]
[ 628692-15-9 ]
[ 1435972-33-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3443 - 3447

71
[ 1431626-43-5 ]
[ 628692-15-9 ]
[ 1013101-57-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2787 - 2792

72
2-[trans-4-(2-amino-6-bromo-4-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)cyclohexyl]oxy}acetamide [ No CAS ]
[ 628692-15-9 ]
[ 1013101-61-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2787 - 2792

73
2-[cis-4-(2-amino-6-bromo-4-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)cyclohexyl]oxy}acetamide [ No CAS ]
[ 628692-15-9 ]
[ 1013101-43-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2787 - 2792

74
2-[trans-4-(2-amino-6-bromo-4-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)cyclohexyl]oxy}acetamide [ No CAS ]
[ 628692-15-9 ]
[ 1013101-37-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2787 - 2792

75
C₁₈H₁₆INO [ No CAS ]
[ 628692-15-9 ]
C₂₃H₂₁N₃O₂ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2013,vol. 15,p. 247 - 254

76
C₁₅H₁₀INO [ No CAS ]
[ 628692-15-9 ]
C₂₀H₁₅N₃O₂ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2013,vol. 15,p. 247 - 254

77
[ 1346245-14-4 ]
[ 628692-15-9 ]
[ 1431703-34-2 ]

Yield	Reaction Conditions	Operation in experiment
73%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; water; at 90℃; for 5h;Inert atmosphere;	A mixture of intermediate 5a (500 mg; 1.02 mmol), 2-methoxypyrimidine-5-boronic acid (237 mg; 1.54 mmol), K3P04 (435 mg; 2.05 mmol) and S-Phos (84 mg; 0.21 mmol) in 1 ,4-dioxane (12.25 ml_) and H20 (5 ml.) was degassed with N2. After 10 min, Pd2(dba)3 (94 mg; 0.10 mmol) was added portionwise. The r.m. was heated at 90°C for 5 h, cooled to r.t., poured onto ice water and extracted with EtOAc. The organic layer was washed with brine, dried over MgS04, filtered and evaporated to dryness. The residue was purified by chromatography over silica gel (Irregular SiOH 15-40pm 300g; mobile phase: 98percent DCM, 2percent MeOH). The pure fractions were collected and evaporated to dryness yielding 420 mg (73percent) of intermediate 56.

Reference： [1]Patent: WO2013/61081,2013,A1 .Location in patent: Page/Page column 181; 182

78
[ 13535-01-8 ]
[ 628692-15-9 ]
[ 1258620-56-2 ]

Yield	Reaction Conditions	Operation in experiment
47.5%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 120℃;Inert atmosphere;	The mixture of 5-bromo-pyriden-3-ylamine (2.6 g, 15 mmol), boronic acid (1.9 g, 12.5 mmol), Pd(PPh3)4 (1.45g, 1.25 mmol), K2C03 (5.18 g, 37.5 mmol) in DMF (50 mL) was stirred at 120°C under N2 overnight. The reaction mixture was concentrated in vacuum. The residue was purified by chromatography on silica gel eluting with EA, to give 1.2 g (yield: 47.5percent) of 5-(2-methoxypyrimidn-5-yl)-3-pyridylamine as yellow solid. [00824] 1H NMR (CDC13, 400 MHz): delta = 8.70 (2H, s), 8.17 (IH, d), 8.13 (IH, d), 7.07 (IH, dd), 4.07 (3H, s).

Reference： [1]Patent: WO2013/126608,2013,A1 .Location in patent: Paragraph 00823-00824

79
[ 13535-01-8 ]
[ 628692-15-9 ]
[ 1451274-22-8 ]

Reference： [1]Patent: WO2013/126608,2013,A1

80
C₁₉H₁₅BrN₄OS [ No CAS ]
[ 628692-15-9 ]
C₂₄H₂₀N₆O₂S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6172 - 6177

81
3-iodo-4-methyl-N-(4-(trifluoromethoxy)phenyl)benzamide [ No CAS ]
[ 628692-15-9 ]
3-(2-methoxypyrimidin-5-yl)-4-methyl-N-(4-(trifluoromethoxy)phenyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 125℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	3-Iodo-4-methyl-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 13.1, 84 mg, 0.2 mmol), <strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (61.6 mg, 0.4 mmol), Na2CC>3 (63.6 mg, 0.600 mmol), Pd(PPh3)2Cl2 (7.02 mg, 10.00 muiotaetaomicron), water (200 mu ), EtOH (133 muGamma) and DME (1 mL) were added to a vial, which was sealed, evacuated / purged with argon and subjected to MW irradiation at 125°C for 20 min The RM was diluted with THF (1 mL) and stirred with Si-Thiol (69.4 mg, 0.100 mmol) for a 2 h. The filtrate was evaporated to dryness under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 4 g, DCM / MeOH + 1percent NH4OH, gradient from 1percent to 15percent MeOH + 1percent NH4OH) to afford the title compound as a beige solid. UPLC-MS (Condition 1) tR = 2.89 min, m/z = 404.1 [M+H]+, m/z = 402.2 [M-H]"; -NuMuRho (400 MHz, DMSO-d6) delta ppm 2.35 (s, 3 H) 3.99 (s, 3 H) 7.37 (d, J=8.6 Hz, 2 H) 7.52 (d, J=8.1 Hz, 1 H) 7.88 (d, J=9.3 Hz, 2 H).7.90 (br. s,br. s, 1 H) 7.93 (dd, 1 H) 8.74 (s, 2 H) 10.36 (s, 1 H).

Reference： [1]Patent: WO2013/171641,2013,A1 .Location in patent: Paragraph 00275

82
2-bromo-N-(4-(trifluoromethoxy)phenyl)isonicotinamide [ No CAS ]
[ 628692-15-9 ]
2-(2-methoxypyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)isonicotinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 12℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	2-Bromo-N-(4-(trifluoromethoxy)phenyl)isonicotinamide (Stage 69.1, 70 mg, 0.194 mmol), 2-methoxypyrimidine boronic acid (45 mg, 0.291 mmol), Pd(PPh3)2Cl2 (5.44 mg, 7.75 muiotaetaomicron), Na2C03 (71.9 mg, 0.678 mmol), water (194 muGamma), EtOH (129 mu) and DME (969 muGamma) were added to a vial, which was sealed, evacuated / purged with argon and subjected to MW irradiation at 125°C for 20 min. The RM was stirred with Si-Thiol (53.8 mg, 0.078 mmol) for 30 min. The resin was filtered off and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (Biotage Silica gel column, 4 g, DCM / MeOH + 1percent NH40H from 1.5percent to 20percent MeOH + 1percent NH40H) to yield the title compound as an off-white solid. UPLC-MS (Condition 1) tR2.58 min, m/z = 391 [M+H]+; XH-NMR (400 MHz, DMSO-d6) delta ppm 4.01 (s, 3 H) 7.42 (d, J=8.56 Hz, 2 H) 7.84 (dd, J=5.01, 1.35 Hz, 1 H) 7.90 (m, J=9.30 Hz, 2 H) 8.46 (s, 1 H) 8.89 (d, J=5.14 Hz, 1 H) 9.34 (s, 2 H) 10.71 (s, 1 H).

Reference： [1]Patent: WO2013/171641,2013,A1 .Location in patent: Paragraph 00351

83
5-bromo-6-((3-hydroxypropyl)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide [ No CAS ]
[ 628692-15-9 ]
2-((3-hydroxypropyl)amino)-6'-methoxy-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 125℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	[00528] A mixture of 5-bromo-6-((3-hydroxypropyl)amino)-N-(4- (trifluoromethoxy)phenyl)nicotinamide (Stage 161.1, 72 mg, 0.15 mmol), (6-methoxypyridin-3- yl)boronic acid (23.1 mg, 0.15 mmol) and Na2CC>3 (48 mg, 0.450 mmol) in a mixture of DME (3.2 mL), EtOH (0.43 niL) and water (0.64 mL) was flushed with argon for 5 min. Pd(PPh3)2Cl2 was added (5.3 mg, 0.0075 mmol) and the mixture subjected to MW irradiation at 125°C for 20 min. The vial was cooled to RT and the RM was evaporated to dryness under reduced pressure to give a residue that was triturated with THF and filtered. The filtrate was evaporated to dryness under reduced pressure and the crude product was purified by preparative LC-MS. TFA was removed using a SPE PL-HCO3 (StratoSpheres? VariPure IPE) cartridge to afford the title compound. UPLC-MS (Condition 8) tR = 2.33 min, m/z = 463.1 [M+H]+, m/z = 461.1 [M-H]\

Reference： [1]Patent: WO2013/171640,2013,A1 .Location in patent: Paragraph 00528

84
5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide [ No CAS ]
[ 628692-15-9 ]
6-(3-hydroxypyrrolidin-1-yl)-5-(2-methoxypyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 80℃; for 2h;Microwave irradiation; Sealed tube; Inert atmosphere;	[00316] 5-bromo-6-(3-hydroxypyrrolidin- 1 -yl)-N-(4- (trifluoromethoxy)phenyl)nicotinamide (60 mg, 0.134 mmol), (6-methoxypyridin-3-yl)boronic acid (62.1 mg, 0.403 mmol), Pd(PPh3)2Cl2 (5.66 mg, 8.07 muiotaetaomicron) and Na2C03 (42.8 mg, 0.403 mmol) were added to a MW vial and treated with a mixture of DME (570 muKappa), water (163 mu^) and EtOH (81 mu). The vial was sealed, evacuated / purged with argon and the RM was subjected to MW irradiation at 80°C for 2 h. The RM was cooled to RT, diluted with THF (2 mL), treated with Si-Thiol (Silicycle, 1.27 mmol/g, 52.9 mg, 0.067 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 13, from 25percent to 55percent in 12 min) to afford the title compound as an off- white solid. UPLC-MS (condition 1) tR = 2.19 min, m/z = 473.0 [M+H]+, m/z = 474.1 [M-H]"; XH-NMR (400 MHz, DMSO-de) delta ppm 1.68 - 1.80 (m, 1 H) 1.79 - 1.92 (m, 1 H) 2.94 (d, J = 11.00 Hz, 1 H) 3.21 - 3.29 (m, 2 H) 3.35 - 3.46 (m, 1 H) 3.98 (s, 3 H) 4.18 - 4.29 (m, 1 H) 4.87 (br. s, 1 H) 7.35 (d, J = 8.80 Hz, 2 H) 7.85 (d, J = 9.05 Hz, 2 H) 8.02 (d, J = 2.45 Hz, 1 H) 8.67 (s, 2 H) 8.77 (d, J = 2.20 Hz, 1 H) 10.15 (s, 1 H).

Reference： [1]Patent: WO2013/171640,2013,A1 .Location in patent: Paragraph 00316

85
(R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide [ No CAS ]
[ 628692-15-9 ]
(R)-2-(3-hydroxypyrrolidin-1-yl)-6'-methoxy-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In butan-1-ol; at 100℃; for 16h;Microwave irradiation; Sealed tube; Inert atmosphere;	[00352] (R)-5-Bromo-6-(3-hydroxypyrrolidin-l-yl)-N-(4- (trifluoromethoxy)phenyl)nicotinamide (Stage 35.1, 60 mg, 0.134 mmol), (6-methoxypyridin-3- yl)boronic acid (25.2 mg, 0.161 mmol), Pd2(dba)3 (2.463 mg, 2.69 muetaiotaomicron), 2- diclyclohexylphosphino-2',4',6'-triisoprophylbiphenyl (2.56 mg, 5.38 muetaiotaomicron) and K3PO4 (86 mg, 0.403 mmol) were added to a MW vial. The vial was sealed, evacuated / purged with argon, and BuOH (269 muGamma) was added. The RM was stirred at 100°C for 16 h, diluted with THF (1 mL), treated with Si-Thiol (Silicycle, 1.27 mmol/g, 52.9 mg, 0.067 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 12, from 30percent to 60percent in 12 min.) to afford the title compound as a white solid. UPLC- MS (condition 1) tR = 2.36 min, m/z = 475.2 [M+H]+, m/z = 473.2 [M-H]"; XH-NMR (400 MHz, DMSO-de) delta ppm 1.68 - 1.78 (m, 1 H) 1.77 - 1.90 (m, 1 H) 2.93 (d, J = 11.74 Hz, 1 H) 3.18 - 3.26 (m, 2 H) 3.35 - 3.46 (m, 1 H) 3.91 (s, 3 H) 4.20 (br. s, 1 H) 4.83 (d, J = 3.42 Hz, 1 H) 6.91 (d, J = 8.56 Hz, 1 H) 7.34 (d, J = 8.56 Hz, 2 H) 7.72 (dd, J = 8.56, 2.45 Hz, 1 H) 7.86 (d, J = 9.05 Hz, 2 H) 7.97 (d, J = 2.20 Hz, 1 H) 8.21 (d, J = 2.45 Hz, 1 H) 8.74 (d, J = 2.20 Hz, 1 H) 10.14 (s, 1 H).

Reference： [1]Patent: WO2013/171640,2013,A1 .Location in patent: Paragraph 00352

86
[ 1552300-42-1 ]
[ 628692-15-9 ]
[ 1552300-49-8 ]

Yield	Reaction Conditions	Operation in experiment
47%	With bis(triphenylphosphine)palladium(II) chloride; potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 3h;Inert atmosphere;	General procedure: To a mixture of compound 8a (30 mg, 0.076 mmol), (6-methoxypyridin-3-yl)boronic acid (17.4 mg, 0.115 mmol) and potassium carbonate (166 mg, 1.20 mmol) in DMF (3 mL) and water (0.6 mL) was added bis(triphenylphosphine)palladium (II) chloride (11 mg, 0.0152 mmol). The resulting mixture was degassed and stirred at 100 °C under Argon atmosphere for 3 hrs. The reactions were cooled and concentrated in vacuo. The residue was diluted with water (30 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography (silica gel, dichloromethane/methanol/ammonium water 200:10:1, v/v) to give the title compound 9a (29 mg, 90percent yield) as a yellow solid.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 790 - 793

87
[ 1609169-25-6 ]
[ 628692-15-9 ]
[ 1533399-24-4 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 828 - 835

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	628692-15-9	MDL No. :	MFCD03094664
Formula :	C₅H₇BN₂O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YPWAJLGHACDYQS-UHFFFAOYSA-N
M.W :	153.93	Pubchem ID :	2736778
Synonyms :

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.2
Num. rotatable bonds :	2
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	38.35
TPSA :	75.47 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.66 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	-0.59
Log Po/w (WLOGP) :	-1.84
Log Po/w (MLOGP) :	-1.99
Log Po/w (SILICOS-IT) :	-1.62
Consensus Log Po/w :	-1.21

[ CAS No. 628692-15-9 ] {[proInfo.proName]}

Quality Control of [ 628692-15-9 ]

Related Doc. of [ 628692-15-9 ]

Product Details of [ 628692-15-9 ]

Calculated chemistry of [ 628692-15-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 628692-15-9 ]

Application In Synthesis of [ 628692-15-9 ]

[ 628692-15-9 ] Synthesis Path-Upstream 1~2

[ 628692-15-9 ] Synthesis Path-Downstream 1~87

Related Functional Groups of
[ 628692-15-9 ]

Organoboron

Ethers

Related Parent Nucleus of
[ 628692-15-9 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-0.69
Solubility :	31.1 mg/ml ; 0.202 mol/l
Class :	Very soluble
Log S (Ali) :	-0.52
Solubility :	46.1 mg/ml ; 0.299 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.66
Solubility :	34.1 mg/ml ; 0.221 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.13

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P264-P270-P280-P301+P312+P330-P305+P351+P338-P337+P313-P501	UN#:	N/A
Hazard Statements:	H302-H319	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 628692-15-9 ] {[proInfo.proName]}

Quality Control of [ 628692-15-9 ]

Related Doc. of [ 628692-15-9 ]

Product Details of [ 628692-15-9 ]

Calculated chemistry of [ 628692-15-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 628692-15-9 ]

Application In Synthesis of [ 628692-15-9 ]

[ 628692-15-9 ] Synthesis Path-Upstream 1~2

[ 628692-15-9 ] Synthesis Path-Downstream 1~87

Related Functional Groups of [ 628692-15-9 ]

Organoboron

Ethers

Related Parent Nucleus of [ 628692-15-9 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 628692-15-9 ]

Related Parent Nucleus of
[ 628692-15-9 ]