[ CAS No. 109299-78-7 ] {[proInfo.proName]}

Name: 109299-78-7|Pyrimidin-5-ylboronic acid|98%
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Quality Control of [ 109299-78-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 109299-78-7 ]

CAS No. :	109299-78-7	MDL No. :	MFCD03002366
Formula :	C₄H₅BN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HZFPPBMKGYINDF-UHFFFAOYSA-N
M.W :	123.91	Pubchem ID :	2795193
Synonyms :		Chemical Name :	Pyrimidin-5-ylboronic acid

Calculated chemistry of [ 109299-78-7 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	31.86
TPSA :	66.24 Å²

Pharmacokinetics

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) :	-7.69 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	-0.89
Log Po/w (WLOGP) :	-1.84
Log Po/w (MLOGP) :	-2.25
Log Po/w (SILICOS-IT) :	-1.51
Consensus Log Po/w :	-1.3

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.47
Solubility :	41.5 mg/ml ; 0.335 mol/l
Class :	Very soluble
Log S (Ali) :	-0.02
Solubility :	119.0 mg/ml ; 0.958 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.5
Solubility :	39.3 mg/ml ; 0.317 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.74

Safety of [ 109299-78-7 ]

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

Application In Synthesis of [ 109299-78-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 109299-78-7 ]
Downstream synthetic route of [ 109299-78-7 ]

[ 109299-78-7 ] Synthesis Path-Upstream 1~6

1
[ 109299-78-7 ]
[ 26456-59-7 ]

Reference： [1] Journal of the American Chemical Society, [2] Journal of the American Chemical Society, 2009, vol. 131, p. 4174 - 4175

2
[ 1003015-89-1 ]
[ 14221-01-3 ]
[ 109299-78-7 ]
[ 26456-59-7 ]
[ 1134120-38-9 ]
[ 98511-61-6 ]

Reference： [1] Journal of the American Chemical Society, [2] Journal of the American Chemical Society, 2009, vol. 131, p. 4174 - 4175

3
[ 75-05-8 ]
[ 109299-78-7 ]
[ 40805-79-6 ]

Reference： [1] Chemistry - A European Journal, 2015, vol. 21, # 38, p. 13246 - 13252

4
[ 4595-59-9 ]
[ 109299-78-7 ]

Yield	Reaction Conditions	Operation in experiment
44%	Stage #1: With n-butyllithium; Triisopropyl borate In tetrahydrofuran; hexane; toluene at -70 - -20℃; for 0.5 h; Stage #2: With hydrogenchloride; water In tetrahydrofuran; hexane; toluene at -20 - 20℃; Stage #3: With potassium hydroxide In water	5-Pyrimidineboronic acid; "BuLi (3.02 ml, 2M solution in hexane, 7.55 mmol) was added dropwise to a stirring solution of 5-bromopyrimidine (1 g, 6.29 mmol) and triisopropylborate (1.46 ml, 7.55 mmol) in anhydrous toluene (16 ml) and anhydrous THF (4 ml) at-70°C under a nitrogen atmosphere. The reaction mixture was stirred at-70°C for 30 mins and then removed from the cold bath. When the internal temp. reached-20°C, the reaction was quenched by the dropwise addition of 2M HCI (10 ml). The mixture was allowed to warm to RT and then separated. The aqueous phase was taken to pH 5.5 with 2M KOH and extracted into THF (3 x 25 ml). The combined organic extracts were dried (MgS04), filtered and concentrated in vacuo to provide a colourless solid. The solid was slurried in acetonitrile (2 ml), collected by filtration and dried on the sinter to give the target boronic acid as a brilliant white solid (340 mg, 44percent). 8H(MeOD; 250MHz) 8.98 (2H, s), 9.14 (1H, s).

Reference： [1] Synthetic Communications, 2003, vol. 33, # 5, p. 795 - 800
[2] Organic and Biomolecular Chemistry, 2004, vol. 2, # 6, p. 852 - 857
[3] Patent: WO2005/103019, 2005, A1, . Location in patent: Page/Page column 16
[4] Journal of Organic Chemistry, 2002, vol. 67, # 15, p. 5394 - 5397
[5] Patent: US2006/111394, 2006, A1, . Location in patent: Page/Page column 17

5
[ 4595-59-9 ]
[ 121-43-7 ]
[ 109299-78-7 ]

Yield	Reaction Conditions	Operation in experiment
64%	With n-butyllithium In tetrahydrofuran; hexane; toluene at -78 - -15℃;	To a solution of compound 5-bromopyrimidine (8 g, 50 mmol), trimethyl borate (4.6g, 60 mmol) in toluene and THF (150 mL,V/V=4: 1) was added n-BuLi (24 mL, 60 mmol, 2.5 M in hexane) at <n="135"/>-78⁰C. The reaction mixture was stirred for 1 h at -78⁰C, then warmed to -15⁰C and quenched with 2 N HCl (50 mL, 100 mmol). The mixture was concentrated and purification by chromatography (MeOHrDCM=I : 10) to give pyrimidin-5-ylboronic acid (4 g, 64percent) as light yellow solid. MS (m/z) (IvT+H): 125.

Reference： [1] Patent: WO2009/155527, 2009, A2, . Location in patent: Page/Page column 133-134

6
[ 109299-78-7 ]
[ 1227164-02-4 ]
[ 1227163-84-9 ]

Reference： [1] Patent: US2011/281894, 2011, A1, . Location in patent: Page/Page column 11

[ 109299-78-7 ] Synthesis Path-Downstream 1~88

1
[ 13195-50-1 ]
[ 109299-78-7 ]
[ 58759-03-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2004,vol. 2,p. 852 - 857

2
[ 26452-81-3 ]
[ 109299-78-7 ]
6-methoxy-[4,5']bipyrimidinyl [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 3977 - 3979

3
[ 108-90-7 ]
[ 109299-78-7 ]
[ 34771-45-4 ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 1282 - 1284

4
[ 862730-04-9 ]
[ 109299-78-7 ]
1-isopropyl-3-(pyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃;	Synthesis of 1-isopropyl-3-(pyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (BA53); A solution of 5-Pyrimidinylboronic acid (15 mg, 0.14 mmol) in EtOH (3.3 ml) was added to a solution of <strong>[862730-04-9]3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine</strong> (40 mg, 0.13 mmol) in DME (12 ml). Pd(PPh3)4 (15 mg, 0.015 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80 C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H2O) to yield BA53. ESI-MS (M+H)+ m/z calcd 256.1, found 256.1.

Reference： [1]Patent: US2007/293516,2007,A1 .Location in patent: Page/Page column 15; 19

5
[ 849354-27-4 ]
[ 109299-78-7 ]
1,1,1-trifluoro-4-methyl-4-(5-pyrimidin-5-yl-2,3-dihydrobenzofuran-7-yl)pentan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%		To a mixture OF 4- (5-BROMO-2, 3-DIHYDROBENZOFURAN-7-YL)-1, 1, 1-TRIFLUORO-4-METHYLPENTAN-2-ONE (1.00 g, 2.8 mmol), pyrimidine-5-boronic acid (529 mg, 4. 3 mmol) and potassium carbonate (787 mg) in a sealed tube was added 20 mL of MEOH-DME-DMF (3: 2: 1). After stirring at room temperature for 10 minutes, tetrakis (triphenylphosphine) palladium (0) (329 mg) was added and the reaction mixture was heated at 120 C for 40 minutes. After cooling to room temperature, the crude mixture was filtered through a cotton plug with the aid of ethyl acetate. The filtrate was CONCENTRATED IN VACUO to remove most of the methanol, redissolved in 160 mL of ethyl acetate, and washed with 80 mL of aqueous 1 N sodium hydroxide solution, 80 mL of water, and 80 mL of brine respectively. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated IN VACUO. Purification by column chromatography with 20% to 30% ethyl acetate-hexanes afforded 620 mg (62% yield) of the title compound
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In methanol; DMF (N,N-dimethyl-formamide); 1,2-dimethoxyethane; at 120℃; for 0.666667h;	To a solution of 4-(5-bromo-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one (1.00 g) in 20 mL of DME/MeOH/DMF (2:3:1) in a sealed tube was added pyrimidine-5-boronic acid (529 mg) and potassium carbonate (787 mg) followed by tetrakis(triphenylphosphine)palladium (0) (329 mg) as catalyst. The resulting mixture was heated at 120 C. for 40 minutes. After cooling to room temperature, the crude mixture was filtered through a cotton plug with the aid of EtOAc and concentrated in vacuo to remove most of the methanol. The resulting material was dissolved in 160 mL of EtOAc, washed sequentially with 80 mL of 1 N aqueous sodium hydroxide solution, 80 mL of water, and 80 mL of brine. The organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with 20% to 30% ethyl acetate-hexanes) afforded 1,1,1-trifluoro-4-methyl-4-(5-pyrimidin-5-yl-2,3-dihydrobenzofuran-7-yl)pentan-2-one (620 mg).

Reference： [1]Patent: WO2005/30213,2005,A1 .Location in patent: Page/Page column 219-220
[2]Patent: US2005/234091,2005,A1 .Location in patent: Page/Page column 46-47

6
C₂₀H₁₅BrF₃N₅O [ No CAS ]
[ 109299-78-7 ]
8-(3-Pyrimidin-5-yl-phenyl)-8-(4-trifluoromethoxy-phenyl)-2,3,4,8-tetrahydro-imidazo[1,5-a]pyrimidin-6-yl-cyanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium carbonate;tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine; In 1,2-dimethoxyethane; water; at 85℃; for 1.08333h;	EXAMPLE 29 Preparation of 8-(3-Pyrimidin-5-yl-phenyl)-8-(4-trifluoromethoxy-phenyl)-2,3,4,8-tetrahydro-imidazo[1,5-a]pyrimidin-6-yl-cyanamide A mixture of ethylene glycol dimethyl ether, tris(dibenzylideneacetone)dipalladium (0) (0.014 g, 16.0 mumol), triphenylphosphine (0.008 g, 32.0 mumol) under a nitrogen atmosphere is stirred for 5 min., treated with 2 (0.153 g, 0.320 mmol), pyrimidine-5-boronic acid (0.047 g, 0.380 mmol), sodium carbonate (0.101 g, 0.96 mmol) and water (2 mL), heated at 85 C. for 1 hr, cooled to room temperature and concentrated. the resultant residue is purified by flash chromatography (silica, 97.5:2.5:0.5 methylene chloride/methanol/concentrated ammonium hydroxide as eluent) to afford the title compound as a white solid, 0.130 g (85% yield), mp 227-231 C.; identified by NMR and mass spectral analyses. 1H NMR (500 MHz, CD3OD) delta 9.13 (s, 1H), 9.02 (s, 2H), 7.77 (d, J=7.5 Hz, 1H), 7.71 (s, 1H), 7.62 (dd, J=7.9, 7.6 Hz, 1H) 7.57 (d, J=8.0 Hz, 1H), 7.50 (d, J=8.9 Hz, 2H), 7.33 (d, J=8.3 Hz, 2H), 3.70 (m, 2H), 3.58 (m, 2H), 1.89 (m, 2H); IR (ATR) 3106, 2187, 1622, 1500, 1412, 1256, 1218, 1159 cm-1; ESI MS m/z 478 [C24H18F3N7O+H

Reference： [1]Patent: US2005/282826,2005,A1 .Location in patent: Page/Page column 14

7
[ 872624-52-7 ]
[ 109299-78-7 ]
2-amino-5-pyrimidin-5-yl-4-trifluoromethyl-benzoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; for 36h;Heating / reflux;	Example 78:; N-(2,4-Dioxo-6-pyrimidin-5-yl-7-trifluoromethyl-l,4-dihydro-2H-quinazolin-3-yI)- methanesulfonamide; 2-Amino-5-pyrimidin-5-yl-4-trifluoromethyl-benzoic acid methyl ester; To a solution of <strong>[872624-52-7]2-amino-5-iodo-4-trifluoromethyl-benzoic acid methyl ester</strong> (1.5 g, 4.35 mmol) in DME (50 mL) were added pyrimidine-5-boronic acid (538.7 mg, 4.35 mmol), Pd(dppf)Cl2-CH2Cl2 (355 mg, 0.43 mmol), Cs2CO3 (2.8 g, 8.7 mmol) and the resultant mixture was stirred at reflux temperature for 36 h. The solvent was removed in vacuo and the residue was purified by flash chromatography (120 g silica gel, hexanes ? EtOAc/hexanes (3:7 to 1:1)) to furnish the title product (528 mg, 41%) as a beige solid. API-ES: m/z 298 [M+H]+, rt 4.06 min.

Reference： [1]Patent: WO2006/108591,2006,A1 .Location in patent: Page/Page column 140-141

8
[ 54453-94-0 ]
[ 109299-78-7 ]
[ 918144-17-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃;	To a solution of 6-chloro-2,4-dimethyl-nicotinic acid ethyl ester (0.30 g, 1.40 mmol) and 5-pyriniidine boronic acid (0.522 g, 4.21 mmol) in argon-degassed DME/2 M Na2CO3 (4:1, 12.5 ml) was added Pd(PPh3)4 (162 mg, 0.14 mmol) and the mixture heated to 90C overnight. The reaction was cooled, diluted with EtOAc (25 ml) and H2O (15 ml). The aqueous layer was extracted with EtOAc (2 x 10 ml) and the combined organic extracts were dried (Na2SO4), concentrated and purified by column chromatography on silica gel (Hexanes/EtOAc, 3:2) to afford 2,4-dimethyl-6-pyrimidin-5-yl-nicotinic acid ethyl ester (306 mg, 85%). 1H NMR (CDCl3) delta 1.43 (t, 3H, J= 6 Hz), 2.44 (s, 3H), 2.64 (s, 3H), 4.47 (q, 2H, J= 6 Hz), 7.44 (s, IH), 9.26 (s, IH), 9.32 (s, 2H).

Reference： [1]Patent: WO2006/138350,2006,A2 .Location in patent: Page/Page column 192-193

9
2-amino-5-(3-bromophenyl)-5-(1-ethyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one [ No CAS ]
[ 109299-78-7 ]
2-amino-5-(1-ethyl-1H-pyrrol-3-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 20℃; for 1h;Heating / reflux;	EXAMPLE 52; Preparation of 2-amino-5-(1-ethyl-1H-pyrrol-3-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one; To a solution of 2-amino-5-(3-bromophenyl)-5-(1-ethyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one (80 mg, 0.22 mmol) in DME (3 mL) is added pyrimidin-5-ylboronic acid (57 mg, 0.44 mmol), tetrakis(triphenylphosphine)palladium (25 mg, 0.022 mmo) and a solution sodium carbonate (93 mg, 0.88 mmol) in H2O (0.5 mL) at room temperature. The reaction mixture is refluxed for 1 h and cooled. After evaporation of the solvent, the crude material is purified by chromatography (silica gel, EtOAc/2M ethanolic NH3: 92/8) to give the title compound (60 mg, 75%) as a solid. mp: 100-102 C.; MS(+) ES: 361 (M+H)+.

Reference： [1]Patent: US2007/4786,2007,A1 .Location in patent: Page/Page column 28

10
4-[2-Amino-4-(3-bromo-4-fluoro-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoro-ethyl)-1H-pyrrole-2-carboxylic acid methyl ester [ No CAS ]
[ 109299-78-7 ]
4-[2-amino-4-(4-fluoro-3-pyrimidin-5-yl-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoro-ethyl)-1h-pyrrole-2-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With sodium carbonate;tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine; In methanol; toluene; at 20 - 110℃; for 18.25h;	Step f); 4-[2-Amino-4-(4-fluoro-3-pyrimidin-5-yl-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoro-ethyl)-1H-pyrrole-2-carboxylic acid methyl ester; In a pressure tube was put 2 mL of MeOH and 2 mL of toluene. The solution was degassed with argon and 7.5 mg (0.008 mmol) of Pd2(dba)3 and 8.6 mg of triphenylphosphine was added under an argon atmosphere. After 15 min stirring at room temperature, 47.0 mg (0.38 mmol) of 5-pyrimidyl-boronic acid, 83 mg (0.78 mmol) of Na2CO3, and 125 mg (0.27 mmol) of 4-[2-Amino-4-(3-bromo-4-fluoro-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoro-ethyl)-1H-pyrrole-2-carboxylic acid methyl ester was added and the reaction sealed heated to 110 C. for 18 h. The reaction mixture was cooled, diluted with 100 mL of CHCl3, filtered through celite and the solvent removed at reduced pressure. Chromatography on silica gel using a gradient of EtOAc to 2%-8% MeOH-EtOAc yielded 0.08 gm (64% yield) of a white solid (mp 88-90 C.). 1H NMR (500 MHz, CDCl3) delta: 3.15 (s, 3H), 3.73 (s, 3H), 4.50 (m, 1H), 4.58 (m, 2H), 4.68 (m, 1H), 6.96 (s, 2H), 7.16 (t, 1H, J=8.66 Hz), 7.65 (m, 2H), 8.88 (m, 2H), 9.15 (s, 1H). MS (ESI) m/z 455.1 ([M+H])+; MS (ESI) m/z 453.1 ([M-H])-.

Reference： [1]Patent: US2007/4786,2007,A1 .Location in patent: Page/Page column 42-43; 44

11
C₁₄H₁₄BrN₅O [ No CAS ]
[ 109299-78-7 ]
2-amino-3-methyl-5-(1-methyl-1H-pyrazol-4-yl)-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 4h;	Step f) Preparation of 2-Amino-3-methyl-5-(1-methyl-1H-pyrazol-4-yl)-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4-imidazol-4-one; A mixture of 7 (0.100 g, 0.287 mmol), 5-pyrimidine boronic acid (0.043 g, 0.345 mmol), tetrakistriphenylphosphinopalladium(0) (0.017 g, 0.0144 mmol) and potassium carbonate (0.099 g, 0.718 mmol) in 5:1 dioxane/water (1.8 mL) was heated at 100 C. for 4 h. The mixture was cooled to room temperature, concentrated and the crude product purified by flash chromatography (silica, 95:5:0.25 methylene chloride/methanol/concentrated ammonium hydroxide) to afford the title compound (0.060 g, 60%) as a white solid: Rf 0.36 (92:8:0.25 methylene chloride/methanol/concentrated ammonium hydroxide); 1H NMR (300 MHz, CD3OD) delta 9.13 (s, 1H), 9.01 (s, 2H), 7.75-7.42 (m, 6H), 3.85 (s, 3H), 3.10 (s, 3H); IR (ATR) 1663, 1468, 1413, 1400 cm-1; ESI MS m/z 348 [C18H17N7O+H]+;

Reference： [1]Patent: US2007/4786,2007,A1 .Location in patent: Page/Page column 14
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5164 - 5170

12
C₁₅H₁₄BrN₃OS [ No CAS ]
[ 109299-78-7 ]
2-Amino-5-(2-methylthien-3-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; hexane; for 0.916667h;Heating / reflux;	Step e); Preparation of 2-Amino-5-(2-methylthien-3-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one; A mixture of 24 (0.060 g, 0.166 mmol), 5-pyrimidineboronic acid (0.028 g, 0.224 mmol) and tetrakis(triphenylphosphino)palladium(0) (0.011 g, 92.6 mumol) in dioxane (1.5 mL) was treated with a solution of potassium carbonate (0.074 g, 0.532 mmol) in water (0.3 mL), then heated at reflux for 55 min. The mixture was cooled to room temperature, concentrated, and the residue partitioned between methylene chloride (50 mL) and water (50 mL). The layers were separated, and the aqueous layer was extracted with methylene chloride (2×25 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. Purification by flash chromatography (silica, 96:4:0.5 methylene chloride/methanol/concentrated ammonium hydroxide) afforded the title product (0.046 g, 76%) as a white solid: mp 154-159 C.: 1H NMR (500 MHz, CD3OD) delta 9.12 (s, 1H), 9.01 (s, 2H), 7.73 (d, J=1.8 Hz, 1H), 7.68-7.65 (m, 1H), 7.58-7.51 (m, 2H), 7.05 (s, 1H), 6.77 (d, J=5.3 Hz, 1H), 3.12 (s, 3H), 2.11 (s, 3H); ESI MS m/z 364 [C19H17N5OS+H

Reference： [1]Patent: US2007/4786,2007,A1 .Location in patent: Page/Page column 18; 19
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5164 - 5170

13
cis-3-(6-bromo-benzothiazol-2-yl)-cyclobutanol [ No CAS ]
[ 109299-78-7 ]
cis-3-(6-pyrimidin-5-yl-1,3-benzothiazol-2-yl)cyclobutanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.6%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; CyJohnPhos; In 1,4-dioxane; ethanol; water; at 140℃; for 0.166667h;Microwave irradiation;	Example 81A Cis-3-(6-pyrimidin-5-yl-1,3-benzothiazol-2-yl)cyclobutanol The product of Example 1D (100 mg, 0.35 mmole), pyrimidine-5-boronic acid (65 mg, 0.53 mmole), dichlorobis(triphenylphosphine)palladium(II) (14.8 mg, 0.0021 mmole), 2-(dicyclohexyl-phosphino)biphenyl (7.4 mg, 0.021 mmole), sodium carbonate (1 M solution, 0.53 ml, 0.53 mmole) and 2 ml of ethanol/dioxane (1:1) were mixed under N2 in a capped, sealed vial. The vial was sealed heated in the microwave for 10 minutes at 140 C. using a commercial microwave heating apparatus (i.e. the Emrys Creator). The reaction mixture was quenched with water and extracted with dichloromethane (4*5 ml). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product which was purified by column chromatography (10% methanol in dichloromethane) to give 80.4 mg (84.6% yield) of title compound. 1H NMR (300 MHz, CDCl3) delta ppm 9.25 (s, 1H), 9.03 (s, 2H), 8.14 (d, J=8.48 Hz, 1H), 8.07 (d, J=1.70 Hz, 1H), 7.67 (dd, J=8.48, 2.03 Hz, 1H), 4.40 (m, 1H), 3.50 (m, 1H), 3.01 (m, 2H), 2.46 (m, 2H), 2.17 (brs, 1H). MS: (M+H)+=284.

Reference： [1]Patent: US2007/66588,2007,A1 .Location in patent: Page/Page column 45

14
trans-6-bromo-2-{3-[(2R)-2-methylpyrrolidin-1-yl]cyclobutyl}-1,3-benzothiazole [ No CAS ]
[ 109299-78-7 ]
trans-2-{3-[(2R)-2-methylpyrrolidin-1-yl]cyclobutyl}-6-pyrimidin-5-yl-1,3-benzothiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In isopropyl alcohol; at 85℃;	Example 1F Trans-2-{3-[(2R)-2-methylpyrrolidin-1-yl]cyclobutyl}-6-pyrimidin-5-yl-1,3-benzothiazole A solution of the product of Example 1E (40 mg, 0.114 mmole), pyrimidine-5-boronic acid (CAS # 109299-78-7) (21 mg, 0.169 mmole), dichlorobis(triphenylphosphine)palladium(II) (8 mg, 0.01 mmole) and potassium carbonate (47 mg, 0.34 mmole) in 1 ml isopropanol was heated at 85 C. overnight with stirring. The reaction was then quenched with water and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (eluted by 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane) to give 33 mg (82%/o yield) of title compound. 1H NMR (400 MHz, CDCl3) delta ppm 9.23 (s, 1H), 9.02 (s, 2H), 8.12 (d, J=8.59 Hz, 1H), 8.06 (d, J=1.84 Hz, 1H), 7.67 (dd, J=8.44, 1.99 Hz, 1H), 3.83-3.94 (m, 1H), 3.46-3.62 (m, 1H), 2.99-3.14 (m, 1H), 2.64-2.85 (m, 3H), 2.43-2.64 (m, 2H), 2.23-2.40 (m, 1H), 1.89-2.03 (m, 1H), 1.78-1.91 (m, 1H), 1.67-1.78 (m, 1H), 1.42-1.56 (m, 1H), 1.14 (d, J=4.91 Hz, 3H). MS: (M+H)+=351.

Reference： [1]Patent: US2007/66588,2007,A1 .Location in patent: Page/Page column 29

15
[ 1040275-53-3 ]
[ 109299-78-7 ]
[ 1040280-83-8 ]

Yield	Reaction Conditions	Operation in experiment
62%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 150℃; for 0.166667h;	To a 10 mL microwave vial equipped with a magnetic stir bar was added 8-bromo- 1-(1 H-indol-5-yl)-5,6-dihydrobenzo[f]quinazolin-3-amine (50.0 mgs, 1.0eq) 5- pyrimidinylboronic acid (44.1 mgs, 2.0 eq), and PdCI2(PPh3)2 (7mgs, 0.01eq), in dimethylformamide (3 mLs) and 2N Na2CO3 (1 mL). The reaction mixture was heated to 15O0C for 10 minutes in a microwave. The reaction mixture was allowed to cool to room temperature and then filtered pad of celite. The filter pad was rinsed with EtOAc. The organics were then gravity filtered through an SCX ion exchange column (previously washed with methanol) and resin was washed with <n="74"/>dichloromethane (3x). Wash resin with 2N NH3/MeOH (3x3ml_s) and filtrate was collected. The solvents were removed in vacuo and the crude material was purified on by preparatory HPLC. (10 to 100% acetonitrile/0.02% aqueous NH4OH over 14 min). 31 mgs recovered, 62% yield. 1H NMR (400 MHz, DMSO-D6) delta ppm 2.7 (m, 2 H) 3.0 (m, 2 H) 6.4 (m, 1 H) 6.7 (m, 3 H) 7.1 (dd, J=8.4, 1.5 Hz, 1 H) 7.2 (dd, J=8.4, 2.2 Hz, 1 H) 7.3 (m, 2 H) 7.7 (s, 2 H) 9.1 (s, 2 H) 9.1 (s, 1 H) 1 1.2 (s, 1 H). MS: m/z 391 (M+1 ) +.

Reference： [1]Patent: WO2008/86158,2008,A1 .Location in patent: Page/Page column 72-73

16
[ 1749-68-4 ]
[ 109299-78-7 ]
[ 1061357-99-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 160℃; for 1h;	2-Methyl-4,5'-bipyrimidin-6-amine; To a microwave vial were added <strong>[1749-68-4]6-chloro-2-methylpyrimidin-4-amine</strong> (700 mg, 4.88 mmol), pyrimidin-5-ylboronic acid (725 mg, 5.86 mmol), PdCl2(PPh3)2 ( 684 mg, 0.97 mmol), dioxane (10 mL) and Na2CO3 (2 M, 7 mL, 14 mmol) under Argon. The vial was microwave heated for Ih at 160 C. Water was added, and extracted with 10% MeOH/CHCl3 (3*50mL). The organic layers were combined and concentrated under reduced pressure and the crude was purified by silica gel chromatography to yield the title compound as a white solid; MS (m/z): [M+H]+ 188.2.

Reference： [1]Patent: WO2008/115369,2008,A2 .Location in patent: Page/Page column 115

17
[ 1083179-96-7 ]
[ 109299-78-7 ]
[ 1083179-45-6 ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 120℃; for 0.5h;Microwave irradiation;	2-Amino-5-(3-bromo-4-fluorophenyl)-3-methyl-5-[4-(pentafluoro-lambda6-sulfanyl)phenyl]-3,5-dihydro-4H-imidazol-4-one (0.295 g, 0.60 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (complex with dichloromethane (1:1) (0.024 g, 0.03 mmol), potassium acetate (0.119 g, 1.21 mmol) and <strong>[109299-78-7]pyrimidin-5-yl boronic acid</strong> (0.074 g, 0.60 mmol) were dissolved in degassed DME/water (4:1, 4 mL). The reaction mixture was irradiated in a microwave at 120 C. for 30 minutes. The reaction mixture was filtered through celite, the filtrate was washed with ethyl acetate and concentrated. The residue was dissolved in DMSO (2 mL) and purified by preparative HPLC to give the title compound (0.150 g, 49% yield). 1H NMR (400 MHz, CDCl3) delta ppm 9.22 (s, 1H); 8.91 (d, J=10.3 Hz, 2H); 7.70-7.74 (m, 2H); 7.59-7.69 (m, 4H); 7.20 (t, J=9.3 Hz, 1H); 3.14 (s, 3H); MS (ES) m/z 488,0 [M+H]+.

Reference： [1]Patent: US2008/287460,2008,A1 .Location in patent: Page/Page column 18

18
[ 109299-78-7 ]
[ 302964-08-5 ]
[ 1092367-84-4 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; at 120℃;	N-(2-chloro-6-methylphenyl)-2-(2-methyl-4,5'-bipyrimidin-6-ylamino)thiazole-5- carboxamideTo 2-(6-chloro-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6- methylphenyl)thiazole-5-carboxamide (250 mg, 0.634 mmol) in dioxane (10 mL) was added pyrimidin-5-ylboronic acid (94 mg, 0.759 mmol), PdCl2(PPh3)2 (89 mg, 0.127 mmol) and Na2CO3 (2 M, 1 mL, 1.902 mmol). The mixture was stirred under Argon overnight in an oil bath (12O0C). The reaction mixture was cooled to room temperature and water was added, extracted with 10% MeOH in CHCl3 (3x50 mL). The organic layers were washed with brine and dried over anhydrous Na2SO4. The solvent was removed and the crude was purified with preparative HPLC (ACN/ 0.1 % TFA in water) to obtain the title compound as a yellow solid (180 mg, 52%). 1H-NMR (400 MHz, d6-DMSO) delta 12.31 (br s, IH), 10.02 (s, IH), 9.36 (s, 2H), 9.35 (s, IH), 8.34 (s, IH), 7.43 (s, IH), 7.41 (d, J= 1.6 Hz, IH), 7.32-7.25 (m, 2H), 2.71 (s, 3H), 2.26 (s, 3H); MS (m/z): 438.2 [M+l]+.

Reference： [1]Patent: WO2008/150446,2008,A1 .Location in patent: Page/Page column 36

19
[ 1000201-22-8 ]
[ 109299-78-7 ]
[ 1000200-94-1 ]

Yield	Reaction Conditions	Operation in experiment
61%	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; ethanol; water; at 100℃; for 0.25h;Microwave irradiation 2450 MHz;	A mixture of l-(3-bromophenyl)-6-chloro-l-pyridin-4-yl-lH-isoindol-3-amine (0.24 g, 0.60 mmol), pyrimidine-5-boronic acid (0.11 g, 0.90 mmol), potassium carbonate (0.17 g, 1.20 mmol), [l,r-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (0.025 g, 0.030 mmol), dimethoxyethane (3 mL), water (1.5 mL) and ethanol (0.5 mL) under an argon atmosphere was irradiated in a microwave reactor at 100 0C for 15 min. The reaction mixture was filtered through Celite which was washed with EtOAc, the filtrate was concentrated and the residue was purified by preparative HPLC, HPLC to give the title compound (0.147 g, 61 %). 1U NMR (DMSO-J6) delta 9.06 (s, 1 H), 8.93 (s, 2 H), 8.44 - 8.47 (m, 1 H), 8.33 - 8.37 (m, 2 H), 7.88 (d, J= 1.01 Hz, 2 H), 7.53 - 7.59 (m, 2 H), 7.33 - 7.43 (m, 2 H), 7.19 - 7.24 (m, 2 H), 7.02 (br s, 2 H); MS (ESI) m/z 398 [M+l]+.

Reference： [1]Patent: WO2009/5471,2009,A1 .Location in patent: Page/Page column 37-38

20
[ 1123157-74-3 ]
[ 109299-78-7 ]
[ 1123155-80-5 ]

Yield	Reaction Conditions	Operation in experiment
57%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; at 20 - 160℃; for 0.5h;Microwave irradiation;	Step 2: Preparation of 4-{2-(2-carboxy-ethyl)-3-[6-(3,5-di-pyrimidin-5-yl-phenoxy)-hexyl]-phenoxy}-butyric acid; To a solution of 4-{2-(2-carboxy-ethyl)-3-[6-(3,5-dibromo-phenoxy)-hexyl]-phenoxy}-butyric acid (150 mg, 0.26 mmol) in ethanol (2 mL) in a 20 mL microwave tube were added tetrakis(triphenylphosphine)palladium(0) (29.5 mg, 0.03 mmol), pyrimidin-5-ylboronic acid (189 mg, 3.0 mmol), and potassium carbonate (212 mg, 1.53 mmol) at room temperature. The microwave tube was sealed and heated to 160 C. in a microwave oven for 30 minutes. Then, the reaction mixture was cooled to room temperature and diluted with water (20 mL) and ethyl acetate (20 mL). The two layers were separated and the ethyl acetate layer was discarded. Then, the aqueous layer was acidified with 1.0 N hydrochloric acid and the organic compound was extracted into ethyl acetate (2×20 mL). The combined organic extracts were washed with brine solution (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to afford 4-{2-(2-carboxy-ethyl)-3-[6-(3,5-di-pyrimidin-5-yl-phenoxy)-hexyl]-phenoxy}-butyric acid (85 mg, 57%) as a light yellow solid: ES(+)-HRMS m/e calculated for C33H36N4O6 (M+Na)+ 607.2527, found 607.2527.

Reference： [1]Patent: US2009/54466,2009,A1 .Location in patent: Page/Page column 25
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 3502 - 3516

21
[ 910649-46-6 ]
[ 109299-78-7 ]
[ 1012083-39-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	With benzyltriethylammonium carbonate resin;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In methanol; 1,2-dimethoxyethane; at 120℃; for 0.5h;Microwave irradiation;	Example 1775-(5-Pyrimidinyl)-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranoside; 0.2 g (0.45 mM) of 5-bromo-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranoside, obtained according to preparation IX, 66 mg (0.53 mM) of 5-pyrimidineboronic acid, 0.281 g (0.90 mM) of resin grafted with benzyltriethylammonium carbonate and 36 mg (0.044 mM) of the [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane are mixed in 3 ml of DME and 2 ml of methanol. The reaction mixture is brought to 120 C. for 30 minutes by heating under microwave radiation. After filtering and rinsing the solid residue with methanol, the resulting solution is concentrated under reduced pressure. The evaporation residue is purified by chromatography on a silica column (eluent: dichloromethane/methanol 70/30; v/v) and the product is subsequently recrystallized from isopropanol in order to obtain the expected product in the form of pearlescent pink crystals with a yield of 50%.M.p.=213-217 C.[alpha]D30=-4 (c=0.10; DMSO).

Reference： [1]Patent: US2009/182013,2009,A1 .Location in patent: Page/Page column 24

22
[ 1003015-89-1 ]
[ 14221-01-3 ]
[ 109299-78-7 ]
[ 26456-59-7 ]
[ 1134120-38-9 ]
[ 98511-61-6 ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 4174 - 4175

23
[ 109299-78-7 ]
[ 26456-59-7 ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 4174 - 4175

24
[ 1190379-12-4 ]
[ 109299-78-7 ]
[ 1190378-88-1 ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 100℃;Inert atmosphere;	Example 141 below (100 mg, 0.23 mmol), pyrimidine-5-boronic acid (31 mg, 0.25 mmol), Pd(dppf)Cl2 (9.2 mg, 0.01 mmol) and 2M sodium carbonate (248 mul, 0.50 mmol) were mixed together in dioxane (2 ml) and the solution degassed for 5 min.. The reaction mixture was then stirred at 100 0C under nitrogen overnight. The solvents were evaporated and the crude product was purified by flash chromatography using a Biotage SP4 (DCM/methanol gradient) to give a beige solid (50 mg, 50%). 1H NMR (400 MHz, DMS(W6) delta ppm 0.42 - 0.62 (m, 2 H), 0.84 - 0.90 (m, 2 <n="189"/>H), 1.48 - 1.56 (m, 1 H), 1.66 - 1.81 (m, 3 H), 1.85 - 1.95 (m, 1 H), 1.97 - 2.06 (m, 2 H), 2.09 - 2.19(m, 2 H), 2.95 - 3.04 (m, 1 H), 3.09 - 3.18 (m, 2 H), 3.47 (q, J=6.4 Hz, 2 H), 6.92 (t, 7=6.0 Hz, 1 H), 7.29 (d, 7=8.2 Hz, 1 H), 7.43 (t, 7=8.0 Hz, 1 H), 7.69 (s, 1 H), 7.72 (t, 7=5.7 Hz, 1 H), 7.85 (d, j=9.6 Hz, 1 H), 8.31 (s, 1 H), 9.09 (s, 2 H), 9.12 (s, 1 H), 9.23 (s, 1 H); m/z (ES+APCI)+: 444 [M+H]+

Reference： [1]Patent: WO2009/122180,2009,A1 .Location in patent: Page/Page column 187-188

25
[ 1194044-86-4 ]
[ 109299-78-7 ]
[ 1194044-87-5 ]

Yield	Reaction Conditions	Operation in experiment
46%	With caesium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 97℃; for 0.333333h;	Preparation 26 (S)-N-(4-(4-fluoro-3-(pyrimidin-5-yl)phenyl)-4,6,6-trimethyl-5,6-dihydro-4H-1,3-thiazin-2-yl)benzamide To a 97 C. solution of (S)-N-(4-(3-bromo-4-fluorophenyl)-4,6,6-trimethyl-5,6-dihydro-4H-1,3-thiazin-2-yl)benzamide (0.067 g, 0.15 mmoles, 1.0 equiv) in 1,2-dimethoxyethane (1.5 mL), ethanol (0.7 mL) and water (1.0 mL) is added pyrimidine-5-boronic acid (0.095 g, 0.77 mmoles, 5.0 equiv), cesium carbonate (0.301 g, 0.92 mmoles, 6.1 equiv) and bis(triphenylphoshine)palladium (II) chloride (0.022 g, 0.03 mmoles, 0.2 equiv). The reaction mixture is stirred at 97 C. for 20 minutes. After cooling to room temperature, the reaction mixture is poured into water and extracted with ethyl acetate. The organic phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure. The solvent is removed under reduced pressure and the residue is purified by silica gel flash column chromatography eluding with a linear gradient of dichloromethane to 15% ethyl acetate: dichloromethane to give the title compound (46% yield): MS (m/z): 435 (M+1).

Reference： [1]Patent: US2009/275566,2009,A1 .Location in patent: Page/Page column 15

26
[ 1194044-58-0 ]
[ 109299-78-7 ]
[ 1194044-65-9 ]

Yield	Reaction Conditions	Operation in experiment
67%	With caesium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; at 100℃; for 0.666667h;	Preparation 15 (S)-[4-(2,4-Difluoro-5-pyrimidin-5-yl-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]thiazin-2-yl]-carbamic Acid Tert-Butyl Ester To a 100 C. solution of (S)-4-(5-bromo-2,4-difluorophenyl)-4-methyl-5,6-dihydro-4H-1,3-thiazin-2-amine (12.6 g, 29.9 mmol, 1 equiv) in 1,2-dimethoxyethane:water:ethanol (15:7:5, 300 mL) is added a pyrimidine-5-boronic acid (25 g, 203 mmoles, 6.8 equiv) followed by cesium carbonate (58 g, 180 mmoles, 6 equiv) and bis(triphenylphosphine)palladium(II) chloride (4.2 g, 6.0 moles, 0.2 equiv). After 40 minutes, the reaction is cooled to ambient temperature, diluted with water, and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography eluding with a step gradient of hexanes:ethyl acetate (7:3) to hexanes:ethyl acetate (1:1) to give the title compound (67% yield): MS (m/z): 421 (M+1).

Reference： [1]Patent: US2009/275566,2009,A1 .Location in patent: Page/Page column 12

27
[ 1200525-65-0 ]
[ 109299-78-7 ]
[ 1200525-69-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In propan-1-ol; at 80℃;Inert atmosphere;	Preparation of 5-methoxy-2phiyrimidin-5-yl-indole-3-carbaldehyde; To a stirred solution of Pd(PPh3)4 (0.818 g, 0.7 mmol, 0.1 eq.) in propanol (5 ml_), deoxygenated 2M Na2CO3 (4.2 ml_, 8.5 mmol, 1.2 eq.) was added and the resulting mixture was stirred for 10 minutes at room temperature under argon atmosphere. 2-Bromo-5-methoxy- indole-3-carbaldehyde (1.80 g, 7.08 mmol, 1 eq.) and 5-pyrimidinyl boronic acid (1.05 g, 8.5 mmol, 1.2 eq.) in 1 -propanol (20 ml_) were added and the reaction mixture was stirred for 10 minutes. The temperature was slowly raised to 8O0C and the reaction was stirred overnight. T he reaction mass was cooled to room temperature, quenched with water and extracted with EtOAc. The organic layer was washed with 5% NaHCO3 solution, brine, and dried on anhydrous Na2SO4. Evaporation of the solvent afforded a crude mixture that was purified by silica gel column chromatography (eluent: CHCI3/MeOH 100:0 to 95:5). Yield: 50%. MS (m/z): 254.1 (MH+).

Reference： [1]Patent: WO2010/30727,2010,A1 .Location in patent: Page/Page column 102

28
[ 1198319-49-1 ]
[ 109299-78-7 ]
[ 1198318-99-8 ]

Yield	Reaction Conditions	Operation in experiment
52.1%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 115℃; for 1.33333h;Microwave irradiation; Inert atmosphere;	MS (ES+): 376.0 for C12Hi5BrN4O3SStep 5 : l-ethyl-3- [5-(2-methoxyethoxy)-6-pyrimidin-5-yl [ 1 ,3] thiazolo [5,4-b] pyridin-2- yl]urea (Example 44) In a microwave vial l-(6-bromo-5-(2-methoxyethoxy)thiazolo[5,4-b]pyridin-2-yl)-3- ethylurea (125 mg, 0.33 mmol), pyrimidin-5-ylboronic acid (83 mg, 0.67 mmol) and sodium bicarbonate (56.0 mg, 0.67 mmol) were mixed in DME (8 mL) and water (2 mL). The mixture was purged with N2 for 5-10 min. Added Pd(PPh3)4 (57.7 mg, 0.05 mmol) to the mixture and it was microwaved for lhr 20 min at 115 0C. Reaction mixture was concentrated under vacuum. Added water (10ml) to the residue and extracted thrice with dichloromethane. Organic layers were combined, dried over sodium sulphate and concentrated under vacuum. Residue was purified by flash chromatography on silica gel column using 5%MeOH/DCM as eluent. Pure fractions were combined and evaporated under vacuum to afford pure l-ethyl-3-(5-(2-methoxyethoxy)-6-(pyrimidin-5- yl)thiazolo[5,4-b]pyridin-2-yl)urea (65.0 mg, 52.1 %) as white crystalline material. MS (ES+): 375.1 for Ci6Hi8N6O3S <n="71"/>1H NMR (DMSOD6) delta: 1.10 (t, 3H), 3.20 (qn, 2H), 3.30 (s, 3H), 3.68 (t, 2H), 4.50 (t, 2H), 6.68 (t, IH), 8.20 (s, IH), 9.10 (s, 2H), 9.18 (s, IH), 10.75 (b, IH)

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 8834 - 8848
[2]Patent: WO2009/147431,2009,A1 .Location in patent: Page/Page column 69; 70

29
[ 109299-78-7 ]
[ 71-43-2 ]
[ 34771-45-4 ]

Reference： [1]Tetrahedron,2010,vol. 66,p. 1308 - 1312

30
[ 1221134-70-8 ]
[ 109299-78-7 ]
[ 1221161-47-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 110℃; for 1h;Sealed tube;	A mixture of 1E (3.03g, 10.8 mmol), pyrimidine-5-boronic acid (2.0Og, 16.2 mmol), Pd(PPh3J4 (1.25g, 1.08mmol), K2CO3 (2.98g, 21.6 mmol) in 1:1 DMF-H2O (60 mL) were heated at 110 0C in a sealed tube for 1 h. The reaction concentrated, diluted with water and extracted with DCM (4x). The layers were separated. The combined organic layers were dried over Na2SO4, concentrated and chromatographed (2-5% of NHa-MeOH/DCM) to give the title compound (+/-)-1 (2.74g, 90%). LCMS m/z 281 (MH+).

Reference： [1]Patent: WO2010/42473,2010,A1 .Location in patent: Page/Page column 86; 87; 88

31
[ 1221165-90-7 ]
[ 109299-78-7 ]
[ 1221165-91-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 0.25h;Microwaves;	To a solution of 6F (91.8 mg, 0.17 mmol) in DME-water (3:1 , 1.6 ml_) was added Pd(PPh3)4 (19.7 mg, 0.017 mmol), 5-pyrimidylboronic acid (31.6 mg, 0.255 mmol), and NaHCO3 (1 M solution, 0.34 ml_). The mixture was heated using microwave (120 0C, 15 min) and treated with EtOAc (15 ml_) and 1 N NaOH (5 ml_). The organic layer was dried (Na2SO-O, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (15% EtOAc/Hexanes) to give compound 6G as a white solid (71 mg, 89%, LCMS m/z 470, MH+).

Reference： [1]Patent: WO2010/42473,2010,A1 .Location in patent: Page/Page column 98

32
[ 1224436-05-8 ]
[ 109299-78-7 ]
[ 1224434-53-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; water; at 80℃; for 5h;Inert atmosphere;	Pd(PPh3)2Cl2 (1.2 mg, 0.0017 mmol), 5-pyrimidinylboronic acid (61 mg, 0.49 mmol) and Na2 CO3 (2 M, 0.65 mL, 1.3 mmol) were added consecutively to a stirred solution of (4aR,4bS,6aS,9aS,9bR)-1,4a,6a-trimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,9,9a,9b,10-dodecahydro-1H-indeno[5,4-f]quinolin-7-yl trifluoromethanesulfonate (125 mg, 0.29 mmol) in THF (15 mL). The reaction was heated to 80 C. under N2 for 5 hours. Then cooled to room temperature and partitioned between ethyl acetate (100 mL) and water (100 mL). The layers were separated and the aqueous layer extracted with ethyl acetate (25 mL×3). The combined organic layers were dried over Na2 SO4. After filtration, the organic phase was concentrated under vacuum and the residue was purified by prep-chromatogram to afford (4aR,4bS,6aS,9aS,9bS)-1,4a,6a-trimethyl-7-(pyrimidin-5-yl)-4,4a,4b,5,6,6a,9,9a,9b,10-decahydro-1H-indeno[5,4-f]quinolin-2(3H)-one as a white solid (80 mg, yield 75%). 1H NMR (CDCl3, 400 MHz) major characteristic peaks: delta 9.12 (s, 1H), 8.80 (s, 2H), 6.17 (m, 1H), 5.12 (m, 1H), 3.16 (s, 3H), 1.12 (s, 3H), 1.08 (s, 3H). LC-MS (m/z) 364 [M+H]+.

Reference： [1]Patent: US2010/105700,2010,A1 .Location in patent: Page/Page column 48-49

33
[ 1226799-86-5 ]
[ 109299-78-7 ]
[ 1226799-37-6 ]

Yield	Reaction Conditions	Operation in experiment
55%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 150℃; for 0.25h;Microwave irradiation;	Example 12 5-(4-(Difluoromethoxy)-3,5-dimethylphenyl)-5-(3-(pyrimidin-5-yl)phenyl)-5H-pyrrolo[3,4-b]pyridin-7-amine 5-(3-Bromophenyl)-5-(4-(difluoromethoxy)-3,5-dimethylphenyl)-5H-pyrrolo[3,4-b]pyridin-7-amine (100 mg, 0.22 mmol), pyrimidin-5-ylboronic acid (35.1 mg, 0.28 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (17.82 mg, 0.02 mmol), potassium carbonate 2 M (aq) (0.327 mL, 0.65 mmol) and DMF (2 mL) were microwaved for 15 min at 150 C. The resulting mixture was diluted with brine and EtOAc and the phases separated. The aq phase was extracted with EtOAc (*2), the organics combined, dried (Na2SO4), filtered and concentrated. Purification was achieved by preparative chromatography to give the title compound (55 mg, 55% yield): 1H NMR (600 MHz, DMSO-d6) delta ppm 9.17 (s, 1H), 9.02 (s, 2H), 8.63 (dd, 1H), 8.48 (dd, 1H), 7.67 (s, 1H), 7.64 (d, 1H), 7.53 (d, 1H), 7.43-7.51 (m, 2H), 7.16 (s, 2H), 6.75-7.02 (t, 1H), 6.78 (br s, 2H), 2.16 (s, 6H); MS (ES+) m/z 458 [M+1]+.

Reference： [1]Patent: US2010/125081,2010,A1 .Location in patent: Page/Page column 34-35

34
[ 1226800-02-7 ]
[ 109299-78-7 ]
[ 1226799-57-0 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 90℃; for 16h;Inert atmosphere; Sealed tube;	Example 30 5-(3-Cyclopropyl-4-difluoromethoxy-5-methyl-phenyl)-5-(2-pyrimidin-5-yl-pyridin-4-yl)-5H-pyrrolo[3,4-b]pyridin-7-ylamine A mixture of 5-(2-chloro-pyridin-4-yl)-5-(3-cyclopropyl-4-difluoromethoxy-5-methyl-phenyl)-5H-pyrrolo[3,4-b]pyridin-7-ylamine (0.16 g, 0.36 mmol), pyrimidine-5-boronic acid (67.5 mg, 0.54 mmol), Pd(PPh3)4 (84 mg, 0.073 mmol), Na2CO3 (2M, 1 mL, 2 mmol) in DME (4 mL) was degassed using nitrogen for 15 minutes and then heated at 90 C. in a sealed tube for 16 hours. The mixture was cooled to room temperature, diluted with EtOAc (20 mL) and washed with saturated NaHCO3 solution (10 mL), H2O (10 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford 80 mg (45% yield) of the title compound: 1H NMR (400 MHz, CDCl3) delta ppm 9.21-9.27 (m, 3H) 8.68 (d, 1H) 8.64 (d, 1H) 7.87-7.92 (m, 1H) 7.69 (s, 1H) 7.41 (dd, 1H) 7.22-7.25 (m, 1H) 6.94 (s, 1H) 6.67 (d, 1H) 6.44 (t, 1H) 5.48 (s, 2H) 2.26 (s, 3H) 2.03-2.12 (m, 1H) 0.95 (d, 2H) 0.50-0.59 (m, 2H); MS (ES+) m/z: 485.17 [M+1]+.

Reference： [1]Patent: US2010/125081,2010,A1 .Location in patent: Page/Page column 40

35
[ 1226800-05-0 ]
[ 109299-78-7 ]
[ 1226799-61-6 ]

Yield	Reaction Conditions	Operation in experiment
55%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; ethanol; water; at 100℃; for 1.5h;Inert atmosphere; Sealed tube;	Example 34 5-[4-Difluoromethoxy-3-(2-fluoro-ethyl)-phenyl]-5-(3-pyrimidin-5-yl-phenyl)-5H-pyrrolo[3,4-b]pyridin-7-ylamine A mixture of 5-(3-bromo-phenyl)-5-[4-difluoromethoxy-3-(2-fluoro-ethyl)-phenyl]-5H-pyrrolo[3,4-b]pyridin-7-ylamine (494 mg, 1.04 mmol), pyrimidin-5-ylboronic acid (192.8 mg, 1.56 mmol) and potassium carbonate (430.3 mg, 3.11 mmol) in a mixture of DME, water and ethanol (6:2:1, 15 mL) was degassed using nitrogen for 10 minutes. Pd(dppf)Cl2 (75.9 mg, 0.10 mmol) was added in one portion and the reaction mixture was heated at 100 C. in a sealed tube for 1.5 hours. The mixture was cooled to room temperature, diluted with ethyl acetate (50 mL) and filtered. The filtrate was washed with water, brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC to afford 270 mg (55% yield) of the title compound: 1H NMR (400 MHz, CDCl3) delta ppm 9.17 (s, 1H) 8.85 (s, 2H) 8.66 (d, 1H) 7.92 (d, 1H) 7.18-7.59 (m, 7H) 7.03 (d, 1H) 6.50 (t, 1H) 5.40 (br.s., 2H) 4.62 (t, 1H) 4.50 (t, 1H) 3.04 (m, 1H) 2.97 (m, 1H); 19F NMR (376 MHz, CHLOROFORM-d) delta ppm-82.17, -219.24; MS (ES+) m/z: 476.01 [M+1]+.

Reference： [1]Patent: US2010/125081,2010,A1 .Location in patent: Page/Page column 41

36
[ 1227163-10-1 ]
[ 109299-78-7 ]
[ 1227163-12-3 ]

Yield	Reaction Conditions	Operation in experiment
74%		Example 39i (5-(3-Amino-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol (5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol (338 mg, 0.74 mmol), pyrimidine-5-boronic acid (110 mg, 0.89 mmol), cesium carbonate (726 mg, 2.23 mmol) and dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (60.6 mg, 0.07 mmol) were dissolved in DME:EtOH:water (6:3:1) (5 mL) and irradiated in a microwave oven for 20 min at 150 C. The solvent was evaporated in vacuo and to the residue was added water, 2 M HCl solution to reach pH~7, and EtOAc. The organic phase was collected, dried and filtered. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC to give 250 mg (74%) of the title compound. 1H NMR (500 MHz, DMSO-d6) delta ppm 9.17 (s, 1H) 8.99 (s, 2H) 7.57-7.72 (m, 3H) 7.47-7.57 (m, 1H) 7.45 (d, 2H) 7.15-7.29 (m, 2H) 7.02 (d, 1H) 6.47 (br. s., 2H) 4.85-5.11 (m, 1H) 4.45 (br. s., 2H) 3.61 (s, 3H) 2.13 (s, 3H); MS (ES+) m/z 455 (M+H)+

Reference： [1]Patent: US2010/125082,2010,A1 .Location in patent: Page/Page column 27

37
[ 4269-17-4 ]
[ 109299-78-7 ]
[ 1021018-85-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; In ethanol; at 140℃; for 0.3h;Microwave irradiation;	Stage 1: In a microwave tube, dissolve 0.5 g of <strong>[4269-17-4]4-bromo-fluoren-9-one</strong>, which can be obtained according to J. Amer. Chem. Soc, 57, 2443-6, 1935, in 12 mL of ethanol, then add successively 0.27 g of bis(triphenylphosphine) palladium (II) chloride, 0.25 g of pyrimidino-5-boronic acid and 0.54 mL of triethylamine. After reaction at 140 C. for 18 minutes, concentrate to dryness, take up in dichloromethane and in water, dry over magnesium sulphate, filter and concentrate to dryness. Purify the raw solid obtained by flash chromatography on silica gel (20-40 mum), eluting with a mixture of cyclohexane and ethyl acetate (80-20 by volume). We thus obtain 0.3 g of 4-(pyrimidin-5-yl)-fluoren-9-one in the form of a yellow solid, to be used as it is in the next stage and having the following characteristics:Melting point (Kofler): 188 C.

Reference： [1]Patent: US2010/130503,2010,A1 .Location in patent: Page/Page column 20

38
[ 1227162-91-5 ]
[ 109299-78-7 ]
[ 1227163-68-9 ]

Yield	Reaction Conditions	Operation in experiment
54%	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; ethanol; water; at 150℃; for 0.333333h;Microwave irradiation;	Example 27 4-Fluoro-1-(2-methoxypyridin-4-yl)-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine 1-(3-Bromophenyl)-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-3-amine (100 mg, 0.24 mmol), 5-pyrimidinylboronic acid (31.6 mg, 0.25 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (9.90 mg, 0.01 mmol), cesium carbonate (0.058 mL, 0.73 mmol) and DME:EtOH:water (6:3:1) (3.00 mL) were mixed in a microwave vial and heated in a microwave reactor at 150 C. for 20 min. The resulting product mixture was filtered and purified by preparative-HPLC to give 58 mg (54% yield of the title compound (after pooling and freeze drying of the fractions). 1H NMR (400 MHz, DMSO-d6) delta ppm 9.17 (s, 1H) 9.02 (s, 2H) 8.04 (d, 1H) 7.77 (d, 1 H) 7.68 (dd, 1H) 7.64 (s, 1H) 7.55 (td (m), 1H) 7.47 (d, 2H) 7.28 (t, 1H) 6.91 (dd, 1H) 6.66 (s, 1H) 3.79 (s, 3H) 1.91 (s, 2H); MS (ES+) m/z 412 [M+H]+.

Reference： [1]Patent: US2010/125082,2010,A1 .Location in patent: Page/Page column 42
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

39
[ 1227162-92-6 ]
[ 109299-78-7 ]
[ 1227163-48-5 ]

Yield	Reaction Conditions	Operation in experiment
51%		Example 12 4-Fluoro-1-(4-fluoro-3-(pyrimidin-5-yl)phenyl)-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine 1-(3-Bromo-4-fluorophenyl)-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine (0.30 g, 0.64 mmol) and 5-pyrimidinylboronic acid (0.104 g, 0.84 mmol) in DMF (5.00 mL) was heated to 90 C. under argon atmosphere. Dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.039 g, 0.05 mmol) and aqueous potassium carbonate (2.00 M) (0.961 mL, 1.92 mmol) were added and the resulting mixture was stirred at 90 C. for 1 h. The reaction mixture was cooled to room temperature, and then filtered through a syringe filter and purified by preparative HPLC to give the title compound (0.158 g, 51% yield). 1H NMR (500 MHz, DMSO-d6) delta ppm 9.21 (s, 1H) 8.95 (d, J=1.10 Hz, 2H) 8.70 (d, J=5.20 Hz, 1H) 7.86 (d, J=7.57 Hz, 1H) 7.71 (s, 1H) 7.68 (dd, J=5.20, 1.26 Hz, 1H) 7.55-7.63 (m, 2H) 7.51 (ddd, J=8.63, 4.93, 2.52 Hz, 1H) 7.27-7.41 (m, 2H) 6.83 (br. s., 2H) 1.90 (s, 0.68H); MS (ES+) m/z 468 [M+H]+.

Reference： [1]Patent: US2010/125082,2010,A1 .Location in patent: Page/Page column 37; 38
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

40
[ 1227162-93-7 ]
[ 109299-78-7 ]
[ 1227163-73-6 ]

Yield	Reaction Conditions	Operation in experiment
62%	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; ethanol; water; at 150℃; for 0.333333h;	Example 31 1-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine To a solution of 1-(3-bromophenyl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (97 mg, 0.23 mmol) in DME:EtOH:water (6:3:1) (5 mL) was added pyrimidin-5-ylboronic acid (37.0 mg, 0.30 mmol), dichloro[1,1'-bis(diphenylphosphino)ferrocene]-palladium (II) dichloromethane adduct (9.38 mg, 0.01 mmol) and cesium carbonate (225 mg, 0.69 mmol). The vial was sealed and heated in a microwave reactor at 150 C. for 20 minutes. The reaction was diluted with EtOAc and brine, the layers were separated and the aqueous layer was extracted with EtOAc. The organics were combined, dried (Na2SO4), filtered and the solvent was removed under reduced pressure. The crude was purified by preparative HPLC, appropriate fractions combined and the MeOH removed by evaporation. The remaining aqueous phase was basified by addition of sat. aqueous NaHCO3 (pH~9) and extracted with dichloromethane (*3). The organics were combined, washed once with sat. aqueous NaHCO3, dried (Na2SO4), filtered and evaporated to give 60 mg (62%) of the title compound. 1H NMR (600 MHz, DMSO-d6) delta ppm 9.16 (s, 1H) 9.01 (s, 2H) 8.26 (d, 1H) 7.78 (d, 1 H) 7.64-7.70 (m, 1H) 7.63 (s, 1H) 7.53 (td, 1H) 7.43-7.49 (m, 2H) 7.26 (t, 1H) 7.21 (d, 1H) 7.03 (dd, 1H) 6.62 (br. s., 2H) 1.94-2.03 (m, 1H) 0.78-0.90 (m, 4H); MS (ES+) m/z 422 [M+H]+

Reference： [1]Patent: US2010/125082,2010,A1 .Location in patent: Page/Page column 43
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

41
[ 1227163-02-1 ]
[ 109299-78-7 ]
[ 1227163-83-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; ethanol; water; at 150℃; for 0.666667h;Microwave irradiation;	Example 40 1-(2-(Difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine 1-(3-Bromophenyl)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (0.168 g, 0.39 mmol), 5-pyrimidinylboronic acid (0.063 g, 0.51 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (0.016 g, 0.02 mmol), cesium carbonate (0.093 mL, 1.17 mmol) and DME:EtOH:water (6:3:1) (10.0 mL) were added to a microwave vial and heated at 150 C. in a microwave reactor for 20 min. Additional 5-pyrimidinylboronic acid (0.048 g, 0.39 mmol) was added. The reaction mixture was heated at 150 C. in a microwave reactor for 20 min. The reaction mixture was filtered through a syringe filter, concentrated in vacuo, redissolved in methanol and purified by preparative HPLC to afford the title compound (0.115 g, 60%). 1H NMR (400 MHz, DMSO-d6) delta ppm 9.18 (s, 1H) 9.03 (s, 2H) 8.59 (d, 1H) 7.82 (d, 1 H) 7.70 (dt, 1H) 7.63-7.67 (m, 1H) 7.54-7.61 (m, 2H) 7.44-7.53 (m, 3H) 7.30 (dd, 1H) 6.92 (t, 1H); MS (ES+) m/z 432 [M+H]+.

Reference： [1]Patent: US2010/125082,2010,A1 .Location in patent: Page/Page column 45
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 9346 - 9361,16

42
[ 1227163-22-5 ]
[ 109299-78-7 ]
[ 1227163-95-2 ]

Yield	Reaction Conditions	Operation in experiment
47%	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; ethanol; water; at 150℃; for 0.333333h;Microwave irradiation;	Example 52 1-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amine 1-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (92 mg, 0.22 mmol), 5-pyrimidinylboronic acid (35.0 mg, 0.28 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride (8.87 mg, 10.87 mumol), cesium carbonate (0.052 mL, 0.65 mmol) and DME:EtOH:water (6:3:1) (3.00 mL) were put in a microwave vial and heated at 150 C. in a microwave reactor for 20 min. The mixture was filtered through a syringe filter and purified by prep-HPLC. The desired fractions were pooled and concentrated in vacuo. The residue was redissolved in acetonitrile and water was added. The mixture was freeze dried to give the title compound (46.9 mg, 47%). 1H NMR (400 MHz, DMSO-d6) delta ppm 9.33 (s, 2H) 9.24 (s, 1H) 8.67 (d, 1H) 8.29 (d, 1 H) 7.96 (d, 1H) 7.87 (d, 1H) 7.58 (td, 1H) 7.46 (dd, 1H) 7.31 (dd, 1H) 7.21 (d, 1H) 7.03 (dd, 1H) 6.79 (br. s., 2H) 1.96-2.07 (m, 1H) 0.80-0.96 (m, 4H); MS (ES+) m/z 423 [M+1]+.

Reference： [1]Patent: US2010/125082,2010,A1 .Location in patent: Page/Page column 49

43
2-(4'-bromo-5,6-difluoro-2'-oxospiro[1-benzofuran-3,3'-indol]-1'(2'H)-yl)-N-(2-fluorophenyl)acetamide [ No CAS ]
[ 109299-78-7 ]
2-(5,6-difluoro-2'-oxo-4'-pyrimidin-5-ylspiro[1-benzofuran-3,3'-indol]-1'(2'H)-yl)-N-(2-fluorophenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium carbonate;Pd(PPh3)4; In 1,4-dioxane;	Example 4.2 Synthesis of 2-(5,6-difluoro-2'-oxo-4'-pyrimidin-5-ylspiro[1-benzofuran-3,3'-indol]-1'(2'H)-yl)-N-(2-fluorophenyl)acetamide To a solution of 2-(4'-bromo-5,6-difluoro-2'-oxospiro[1-benzofuran-3,3'-indol]-1'(2'H)-yl)-N-(2-fluorophenyl)acetamide (0.15 g, 0.30 mmol) in anhydrous 1,4-dioxane (5.00 mL) was added Pd(PPh3)4 (0.03 g, 0.03 mmol) and stirred at ambient temperature for 10 min. Pyrimidine-5-boronic acid (0.06 g, 0.45 mmol) and sodium carbonate (0.90 mL of 2 M solution, 1.80 mmol) were added. The reaction mixture was reluxed at 120 C. for 16 h, diluted with ethyl acetate (50.0 mL). The organic layer was washed with water, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/1) to give the title compound (0.13 g, 84%): 1H NMR (300 MHz, CDCl3) delta 9.13 (s, 1H), 8.29-8.10 (m, 3H), 7.62 (s, 1H), 7.44 (t, 1H), 7.16-7.03 (m, 4H), 6.91 (d, 1H), 6.85-6.76 (m, 1H), 6.46-6.37 (m, 1H), 4.85-4.73 (m, 2H), 4.61-4.47 (m, 2H); 13C NMR (75 MHz, CDCl3) delta 177.1, 163.9, 157.7, 156.4, 155.7, 141.9, 132.9, 130.0, 126.0, 124.7, 121.9, 115.0, 111.6, 109.8, 100.2, 79.4, 57.9, 44.7; MS (ES+) m/z 503.5 (M+1).
84%		To a solution of 2-(4'-bromo-5,6-difluoro-2'-oxospiro[1-benzofuran-3,3'-indol]-1'(2' /-/)-yl)-Lambda/-(2-fluorophenyl)acetamide (0.15 g, 0.30 mmol) in anhydrous 1 ,4-dioxane (5.00 mL) was added Pd(PPh3)4 (0.03 g, 0.03 mmol) and stirred at ambient temperature for 10 min. Pyrimidine-5-boronic acid (0.06 g, 0.45 mmol) and sodium carbonate (0.90 mL of 2 M solution, 1.80 mmol) were added. The reaction mixture was reluxed at 120 0C for 16 h, diluted with ethyl acetate (50.0 mL). The organic layer was washed with water, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/1) to give the title compound (0.13 g, 84%): 1H NMR (300 MHz, CDCI3) delta 9.13 (S, 1 H), 8.29-8.10 (m, 3H), 7.62 (s, 1 H), 7.44 (t, 1 H), 7.16-7.03 (m, 4H), 6.91 (d, 1 H), 6.85-6.76 (m, 1 H), 6.46-6.37 (m, 1 H), 4.85-4.73 (m, 2H), 4.61-4.47 (m, 2H); 13C NMR (75 MHz, CDCI3) delta 177.1 , 163.9, 157.7, 156.4, 155.7, 141.9, 132.9, 130.0, 126.0, 124.7, 121.9, 115.0, 111.6, 109.8, 100.2, 79.4, 57.9, 44.7; MS (ES+) m/z 503.5 (M + 1). EPO <DP n="213"/>

Reference： [1]Patent: US2010/173967,2010,A1
[2]Patent: WO2006/110917,2006,A2 .Location in patent: Page/Page column 211

44
[ 1262039-70-2 ]
[ 109299-78-7 ]
[ 1262039-73-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	With caesium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 97℃; for 0.5h;Inert atmosphere;	A solution of N-((4aR,6R,7aS)-7a-(3-bromo-4-fluorophenyl)-6-hydroxy-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-yl)benzamide (0.588 g, 1.31 mmol) in a mixture of 1,2-dimethoxyethane (8 mL), ethanol (4 mL) and water (4 mL) is purged with nitrogen and is heated to 97 C. Pyrimidine-5-boronic acid (0.810 g, 6.54 mmol), cesium carbonate (2.56 g, 7.84 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.184 g, 0.261 mmol) is added in a single portion and the reaction is heated at 97 C. for 30 minutes. The reaction is cooled, diluted with water and is extracted twice with ethyl acetate. The organic layer is dried over sodium sulfate and the crude product is purified by silica gel chromatography with a linear gradient of 0% to 40% ethyl acetate in dichloromethane over 20 minutes to give the title compound (0.464 g, 79%). ES/MS m/e: 449 (M+1).

Reference： [1]Patent: US2011/9395,2011,A1 .Location in patent: Page/Page column 32

45
racemic tert-butyl (4aRS,7aSR)-7a-(3-bromophenyl)-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-ylcarbamate [ No CAS ]
[ 109299-78-7 ]
[ 1262036-78-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; at 100 - 110℃; for 0.333333h;Inert atmosphere;	A mixture of tert-butyl (4aR,7aS)-7a-(3-bromophenyl)-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-ylcarbamate (0.860 g, 2.09 mmol), pyrimidine-5-boronic acid (0.423 g, 3.34 mmol), (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) chloride (0.171 g, 0.209 mmol) in 1,2-dimethoxyethane (10 mL) is heated to 100 C. under nitrogen atmosphere. Aqueous 2 M sodium carbonate (3.14 mL, 6.27 mmol) is added to the reaction mixture by syringe. The resulting mixture is stirred at 110 C. for 20 minutes. The reaction is cooled and extracted three times with dichloromethane and the combined extracts are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography, eluting with a linear gradient of methanol in dichloromethane 0 to 20% over 30 minutes to give the title compound as a freebase (0.482 g, 74%). ES/MS m/e: 311 (M+1).

Reference： [1]Patent: US2011/9395,2011,A1 .Location in patent: Page/Page column 39

46
[ 1262038-39-0 ]
[ 109299-78-7 ]
[ 1262038-86-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With caesium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 97℃; for 0.333333h;Inert atmosphere;	A mixture of tert-butyl 8a-(5-bromo-2,4-difluorophenyl)-4,4a,5,7,8,8a-hexahydropyrano[4,3-d][1,3]thiazin-2-ylcarbamate (0.300 g, 0.647 mmol) in 1,2-dimethoxyethane (10 mL), ethanol (4 mL) and water (5 mL) is purged with nitrogen and heated to 97 C. Pyrimidine-5-boronic acid (0.655 g, 5.18 mmol), cesium carbonate (1.90 g, 5.83 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.091 g, 0.129 mmol) is added in a single portion and the reaction is heated at 97 C. for 20 minutes. The reaction is cooled, diluted with water, and extracted with EtOAc. The organic layer is dried over Na2SO4 and the crude product is purified by silica gel chromatography eluting with a linear gradient of 5% to 100% EtOAc in hexanes to give the title compound (0.258 g, 86%). ES/MS (m/e): 463 (M+1).

Reference： [1]Patent: US2011/9395,2011,A1 .Location in patent: Page/Page column 19

47
[ 1260432-26-5 ]
[ 109299-78-7 ]
[ 1260432-27-6 ]

Yield	Reaction Conditions	Operation in experiment
46%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 130℃; for 0.25h;Inert atmosphere; Sealed tube; Microwave irradiation;	2-(3-Bromophenyl)-2-(4-methoxy-3-methylphenyl)-5-methyl-2H-imidazol-4-amine (300 mg, 0,81 mmol), <strong>[109299-78-7]pyrimidin-5-yl boronic acid</strong> (120 mg, 0,97 mmol), [1,1'- bis(diphenylphosphino)ferrocene]palladium(II) chloride (33,1 mg, 0,04 mmol), 2M aqueous potassium carbonate (1,209 mL, 2,42 mmol) and dioxane (4 mL) were mixed in a vial under Ar. The obtained mixture was heated in a microwave reactor at 130 0C for 15 min. The mixture was diluted with MeOH (5 mL), filtered and purified by preparative HPLC. The product was partitioned between saturated aqueous NaHCO3 and DCM (3 x 3 mL). The organic layer was concentrated to give 2-(4-methoxy-3-methylphenyl)-5-methyl- 2-(3-(pyrimidin-5-yl)phenyl)-2H-imidazol-4-amine 38 mg (46% yield). 1H NMR (500 MHz, DMSO-J6) delta ppm 9.18 (s, 1 H), 9.01 (s, 2 H), 7.81 (t, 1 H), 7.51 - 7.69 (m, 2 H), 7.27 - 7.50 (m, 3 H), 6.79 (d, 1 H), 6.60 (br. s, 2 H), 3.71 (s, 3 H), 2.24 (s, 3 H), 2.08 (s, 3 H); MS (ES) m/z 372 [M+l]+.

Reference： [1]Patent: WO2011/2407,2011,A1 .Location in patent: Page/Page column 90-91
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 9297 - 9311,15

48
[ 1260214-82-1 ]
[ 109299-78-7 ]
[ 1260215-52-8 ]

Yield	Reaction Conditions	Operation in experiment
67%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 80℃; for 2h;	Example 5 2-cyclohexyl-5-methyl-2-(3-(pyrimidin-5-yl)phenyl)-2H-imidazol-4-amine 2-(3-Bromophenyl)-2-cyclohexyl-5-methyl-2H-imidazol-4-amine (60 mg, 0.18 mmol), pyrimidin-5-ylboronic acid (44.5 mg, 0.36 mmol) and bis(triphenylphosphine)- palladium(II) chloride (25.2 mg, 0.04 mmol) were taken up in DME (2 mL) and water (1 mL). Sodium carbonate (IM in water) (0.449 mL, 0.45 mmol) was added and the reaction was heated to 80 0C for 2 h. Preparative HPLC yielded 39.9 mg (67% yield) of the titleo compound: 1H NMR (400 MHz, CDCl3) delta ppm 9.20 (s, 1 H) 8.98 (s, 2 H) 7.84 (s, 1 H) 7.67 - 7.76 (m, 1 H) 7.48 (d, 2 H) 5.19 (br. s., 2 H) 2.31 (s, 3 H) 2.05 - 2.15 (m, 1 H) 1.42 - 1.76 (m, 5 H) 0.86 - 1.26 (m, 5 H); MS (ES+) m/z 334 [M+H]+.

Reference： [1]Patent: WO2011/2408,2011,A1 .Location in patent: Page/Page column 82

49
[ 1260214-94-5 ]
[ 109299-78-7 ]
[ 1260215-56-2 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 80℃; for 2h;	Example 9 2-BenzyI-5-methyI-2-(3-(pyrimidin-5-yI)phenyI)-2H-imidazoI-4-amine 2-Benzyl-2-(3-bromophenyl)-5-methyl-2H-imidazol-4-amine (66.5 mg, 0.19 mmol), pyrimidin-5-ylboronic acid (48.2 mg, 0.39 mmol) and bis(triphenylphosphine)-palladium(II) chloride (27.3 mg, 0.04 mmol) were taken up in DME (1 mL) and water (0.5 mL). Sodium carbonate (IM in water) (0.486 mL, 0.49 mmol) was added and the reaction was heated to 80 C for 2 h. The reaction mixture was extracted with DCM. The combined organic phases were dried over MgSO4, filtered and the solvent evaporated. Preparative HPLC yielded 30 mg (45% yield) of the title compound: MS (ES+) m/z 342 [M+H]+.

Reference： [1]Patent: WO2011/2408,2011,A1 .Location in patent: Page/Page column 84
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 9297 - 9311,15

50
[ 1260248-27-8 ]
[ 109299-78-7 ]
[ 1260248-02-9 ]

Yield	Reaction Conditions	Operation in experiment
56%	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In ethanol; Dimethyl ether; water; at 140℃; for 0.416667h;Microwave irradiation;	Example 15-(4-Methoxy-3,5-dimethylphenyl)-5-(3-(pyrimidin-5-yl)phenyl)-5H-pyrrolo[3,4- b] pyrazin-7-aminePyrimidin-5-ylboronic acid (1.030 g, 8.32 mmol), 5-(3-bromophenyl)-5-(4-methoxy-3,5- dimethylphenyl)-5/f-pyrrolo[3,4-delta]pyrazin-7-amine (1.6 g, 3.78 mmol), cesium carbonate (3.69 g, 11.34 mmol) and dichloro[l,r-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.247 g, 0.30 mmol) were dissolved in DME :EtOH: Water (6:3:1, 12 mL) and irradiated in a microwave reactor for 25 min at 140 0C. EtOAc, water (10 mL) and brine were added. The organic phase was collected, filtered through celite, washed with brine, dried over MgSO4 and concentrated. The residue was dissolved in DMSO and purified using preparative HPLC to give 895 mg (56%) of the title compound.1H NMR (500 MHz, DMSO-J6) delta ppm 9.18 (s, 1 H) 8.97 (s, 2 H) 8.74 (d, 1 H) 8.71 (d, 1 H) 7.89 (t, 1 H) 7.71 - 7.75 (m, 1 H) 7.62 - 7.65 (m, 1 H) 7.47 (t, 1 H) 7.22 (s, 2 H) 7.04 (br. s., 2 H) 3.58 (s, 3 H) 2.13 (s, 6 H); MS (ES) m/z 423 [M+l]+.

Reference： [1]Patent: WO2011/2409,2011,A1 .Location in patent: Page/Page column 49-50

51
[ 1272353-93-1 ]
[ 109299-78-7 ]
[ 1272353-73-7 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 20 - 100℃;Inert atmosphere; Microwave irradiation;	2-Chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (225 mg, 0.649 mmol), pyrimidin-5-ylboronic acid (121 mg, 0.973 mmol), and bis(triphenylphosphine)palladium (II) chloride (23 mg, 0.032 mmol) were combined in a microwave tube which was sealed, evacuated and then backfilled with argon. Under argon, previously degassed dioxane (1 mL) and a sodium carbonate (0.33 mL, 0.330 mmol) in water (0.33 mL) solution were added to the reaction mixture. The resulting mixture was heated under microwave irradiation to 100 C where it was maintained for 60 min. After this time, additional pyrimidin-5-ylboronic acid (91 mg, 0.7773 mmol) and bis (triphenylphosphine)palladium (II) chloride (17 mg, 0.024 mmol) were added. Upon completion of addition, the resulting mixture was heated under microwave irradiation at 100 C for 40 min and then allowed to cool to room temperature where it stirred for 14 h. At the conclusion of this period, the reaction mixture was diluted with 50 mL each of water and ethyl acetate. The organic layer was separated and the aqueous portion was extracted with ethyl acetate. The combined organic portions were washed with 50 mL of brine, dried over Na2S04, decanted and concentrated under reduced pressure to yield a crude residue. The crude residue was purified by ISCO (40 g silica gel column) eluting with 0-5% MeOH over 15 min and then 5% MeOH for 10 min to yield Example 1 (212 mg, 84 %). XH NMR (400 MHz, CDC13) ppm 4.74 (d, J=4.27 Hz, 2 H) 6.73 - 6.81 (m, 1 H) 7.09 - 7.16 (m, 2 H) 7.25 - 7.29 (m, 1 H) 7.44 - 7.52 (m, 5 H) 7.58 (dt, J=7.72, 1.88 Hz, 1 H) 7.73 (dd, J=8.28, 7.28 Hz, 1 H) 7.93 (dd, J=8.28, 1.25 Hz, 1 H) 8.23 - 8.26 (m, 1 H) 9.29 (s, 1 H) 9.78 (s, 2 H). LCMS Method D: retention time 0.76min, [M+l] = 391 ; HPLC Method B: purity 99%, retention time 5.6 min.

Reference： [1]Patent: WO2011/28741,2011,A1 .Location in patent: Page/Page column 205
[2]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 831 - 834

52
10-bromo-2-(1-(2-chlorophenyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine [ No CAS ]
[ 109299-78-7 ]
[ 1282516-11-3 ]

Yield	Reaction Conditions	Operation in experiment
64.2%	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 130℃; for 0.5h;Microwave irradiation; Sealed tube; Inert atmosphere;	Example 565 2-(1-(2-chlorophenyl)-1H-1,2,4-triazol-5-yl)-10-(pyrimidin-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 565 A mixture of 10-bromo-2-(1-(2-chlorophenyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (0.5 mmol), pyrimidin-5-ylboronic acid (200 mg, 0.75 mmol), Cs2CO3 (490 mg, 1.5 mmol) was stirred in dioxane and water (5:1, 3.0 mL) followed by the addition of Pd(dppf)Cl2 (30 mg). The reaction mixture was bubbled with N2 gas for 10 min, the reaction tube was sealed, and the contents were stirred at 130 C. under microwave irradiation for 30 min. The mixture was filtered through celite and the filtrate was concentrated and purified with prep-HPLC to give 565 (283 mg, 64.2%). 1H NMR (CDCl3, 400 MHz): delta 9.25 (s, 1H), 8.81 (s, 2H), 8.09-8.01 (m, 2H), 7.54 (s, 1H), 7.19-7.47 (m, 3H), 7.43-7.41 (dd, J=8 Hz, 2H), 7.11-7.09 (d, J=8 Hz, 1H), 4.47-4.45 (d, J=8 Hz, 4H), MS (ESI) m/z 442.11 [M+H+]

Reference： [1]Patent: US2011/76292,2011,A1 .Location in patent: Page/Page column 292

53
[ 1301612-83-8 ]
[ 109299-78-7 ]
[ 1301612-90-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 120℃; for 0.333333h;Sealed tube; Microwave irradiation; Inert atmosphere;	Step 1: tert-Butyl 1-(4-(7-phenyl-2-(pynmidin-5-yl)furo[2,3-b]pyrazin-6- yl)phenyl)cyclobutylcarbamate: Tetrakis(triphenylphosphine)palladium(0) (4.1 mg, 0.004 mmol) was added to a pre-degassed (bubbling nitrogen) solution of fe/ -butyl 1-(4-(2- chloro-7-phenylfuro[2,3-/3]pyrazin-6-yl)phenyl)cyclobutylcarbamate (33.6 mg, 0.071 mmol), pyrimidine-5-boronic acid (13.1 mg, 0.106 mmol) and potassium phosphate, tribasic (45.0 mg, 0.212 mmot) in DMF (1.0 ml)/water (0.25 ml) at RT in a microwave vial. The reaction vessel was sealed and subjected to microwave irradiation at 20 C for 20 minutes with stirring. LCMS showed complete conversion to product. The reaction mixture was partitioned between EtOAc and 1 :1 brine/water, separated, extracted (EtOAc x 2), dried (Phase Separator), solvents removed in vacuo and purified by flash chromatography (Si02, 0-50%, EtOAc in cyclohexane) to give the title compound (28.5 mg, 78%) as a pale yellow solid. LCMS (Method A): RT = 7.61 min, M+H+ = 520.3.

Reference： [1]Patent: WO2011/55115,2011,A1 .Location in patent: Page/Page column 204

54
2-amino-7'-bromo-1,3',3'-trimethyl-2'H-spiro[imidazole-4,1'-naphthalene]-4',5(1H,3'H)-dione 2,2,2-trifluoroacetate [ No CAS ]
[ 76-05-1 ]
[ 109299-78-7 ]
[ 1338093-56-3 ]

Yield	Reaction Conditions	Operation in experiment
85%		A solution of 2-amino-7'-bromo-l,3',3,-trimethyl-2'H- spiro[imidazole-4,l*-naphthalene]-4',5(lH,3'H)-dione 2,2,2-trifluoroacetate (26 mg, 0.0560 mmol), pyrimidin-5-ylboronic acid (9.72 mg, 0.0784 mmol), Pd(PPh3)4 (6.47 mg, 0.00560 mmol), Na2C03 (112 mu, 0.224 mmol; 2M aqueous) in dioxane (280 mu, 0.0560 mmol) was degassed with nitrogen for 5 minutes, sealed in a vial and stirred at 80C for 1 day. The reaction mixture was filtered, and the filtrate was purified by C18 semi -prep HPLC eluting with 5-95% ACN/H20 +0.1% TFA. The product containing fractions was concentrated in vacuo to afford 2-amino-l,3',3'-trimethyl-7'-(pyrimidin-5-yl)-2'H-spiro[imidazole-4,r- naphthalene]-4',5(lH,3'H)-dione 2,2,2-trifluoroacetate (22 mg, 0.0475 mmol, 85%). m/z 350.1 (100%), 351.1 (20%).

Reference： [1]Patent: WO2011/123674,2011,A1 .Location in patent: Page/Page column 158

55
[ 1338094-89-5 ]
[ 76-05-1 ]
[ 109299-78-7 ]
[ 1338093-58-5 ]

Yield	Reaction Conditions	Operation in experiment
87%		A solution of 2-amino-7'-bromo-4',4,-difluoro-l,3,,3'-trimethyl-3',4'- dihydro-2'H-spiro[imidazole-4,l'-naphthalen]-5(lH)-one 2,2,2-trifluoroacetate (3 mg, 0.00617 mmol), pyrimidin-5-ylboronic acid (1.07 mg, 0.00864 mmol), Pd(PPh3)4 (0.713 mg, 0.000617 mmol), Na2C03 (12.3 ih, 0.0247 mmol; 2M aqueous) in dioxane (30.8 mu,, 0.00617 mmol) was degassed with nitrogen for 1 minute, sealed in a vial and stirred at 80C for 1 day. The reaction mixture was filtered and purified by CI 8 semi-prep HPLC eluting with 5-95% ACN/H20 + 0.1% TFA. The product containing fractions were concentrated in vacuo to afford 2-amino-4',4,-difluoro-l,3',3'-trimethyl-7'-(pyrimidin-5-yl)-3',4'-dihydro-2'H- spiro[imidazole-4,l'-naphthalen]-5(lH)-one 2,2,2-trifluoroacetate (2.6 mg, 0.00536 mmol, 87%). m/z 372.1 (40%), 352.1 (100%).

Reference： [1]Patent: WO2011/123674,2011,A1 .Location in patent: Page/Page column 159

56
[ 1338094-33-9 ]
[ 109299-78-7 ]
[ 1338092-74-2 ]

Yield	Reaction Conditions	Operation in experiment
75.7%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 17h;	(R)-2-Amino-7'-bromo- 1,3 ',3 '-trimethyl-3 4'-dihydro-2'H- spiro[imidazole-4, -naphthalen]-5(lH)-one (1.00 g, 2.97 mmol), pyrimidin-5-ylboronic acid (0.479 g, 3.87 mmol), and Pd(PPh3)4 (0.0859 g, 0.0744 mmol) were combined with dioxane (15 mL) and 2M Na2C03 (3.72 mL, 7.44 mmol) (both degassed with nitrogen sparge for 30 min prior to use), and the reaction mixture was heated in a 100C reaction block and stirred for 17 hours. The reaction mixture was then concentrated, and the residue was combined with ethyl acetate and water. The mixture was extracted with ethyl acetate (2 X), and the combined extracts were dried (Na2S04), filtered, and concentrated. The crude was purified on silica gel (5-20% MeOH in dichloromethane gradient) to give (R)-2-amino-l ,3',3'- trimethyl-7'-(pyrimidin-5-yl)-3',4'-dihydro-2'H-spiro[imidazole-4,r-naphthalen]-5(lH)-one (0.755 g, 2.25 mmol, 75.7% yield) as a powder. NMR (400 MHz, CDC13) delta 9.16 (s, 1H), 8.83 (s, 2H), 7.40 (dd, J = 7.8, 2.0 Hz, 1H), 7.25 (d, J = 7.8 Hz, 1H), 7.08 (d, J = 1.6 Hz, 1H), 5.09 (br s, 2H), 3.18 (s, 3H), 2.85 (d, J = 16.4 Hz, 1H), 2.62 (dd, J = 16.0, 2.3 Hz, 1H), 2.29 (d, J = 13.7 Hz, 1 H), 1.80 (dd, J = 13.7, 2.3 Hz, 1 H), 1.17 (s, 3H), 1.01 (s, 3H); m/z (APCI- pos) M+l = 336.

Reference： [1]Patent: WO2011/123674,2011,A1 .Location in patent: Page/Page column 106-107

57
[ 1338094-52-2 ]
[ 109299-78-7 ]
[ 1338092-88-8 ]

Yield	Reaction Conditions	Operation in experiment
77%		7-Bromo-3,3-dimethyl-3,4,5',6'-tetrahydro-2H-spiro[naphthalene-l ,4'- [l,3]oxazin]-2'-amine (0.0195 g, 0.0603 mmol) and pyrimidin-5-ylboronic acid (0.011 g, 0.090 mmol) were dissolved in dioxane (0.8 mL), and a saturated sodium carbonate (0.09 g, 0.170 mmol) solution was added. The reaction was degassed with Ar for 10 minutes. PdCl2 (dppf)2 (0.002 mg, 0.002 mmol) was added, and the vial was sealed under Ar and heated at 80C for 14 hours. The reaction was diluted with EtOAc, washed with water (2 X), brine, dried (MgS04) and concentrated. The crude product was purified by column chromatography (5 to 10% MeOH/CH2Cl2 with 5% NH4OH in MeOH) to provide 3,3- dimethyl-7-(pyrimidin-5-yl)-3,4,5',6'-tetrahydro-2H-spiro[naphthalene-l,4'-[l,3]oxazin]-2'- amine (15 mg, 77%). MS: m/z (APCI-pos) M+l = 323.

Reference： [1]Patent: WO2011/123674,2011,A1 .Location in patent: Page/Page column 118

58
[ 102568-21-8 ]
[ 109299-78-7 ]
[ 1338094-95-3 ]

Yield	Reaction Conditions	Operation in experiment
68%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In dioxane-1,4-; water; at 100℃; for 3.01667h;	A round bottom flask was charged with 7-bromo-3,3-dimethyl-3,4- dihydronaphthalen-l(2H)-one (2.66 g, 10.5 mmol), 1.4-dioxane (32.8 mL), water (15.1 mL), pyrimidin-5-ylboronic acid (1.43 g, 11.6 mmol), Pd(PPh3) (607 mg, 0.525 mmol) and sodium carbonate (3.34 g, 31.5 mmol). The mixture was sparged with N2 for 1 minute and then heated to 100C for 3 hours with stirring. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and washed with saturated aqueous sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by silica gel chromatography eluting with a linear gradient of 0-70% heptane / ethyl acetate to yield 3,3-dimethyl-7-(pyrimidin-5-yl)-3,4- dihydronaphthalen-l(2H)-one (1.80 g, 7.13 mmol, 68% yield).

Reference： [1]Patent: WO2011/123674,2011,A1 .Location in patent: Page/Page column 163

59
isopropyl 4-((1r,4r)-4-(6-bromo-2-methylpyridin-3-yloxy)cyclohexyloxy)piperidine-1-carboxylate [ No CAS ]
[ 109299-78-7 ]
isopropyl 4-((1r,4r)-4-(2-methyl-6-(pyrimidin-5-yl)pyridin-3-yloxy)cyclohexyloxy)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55.5%	With caesium carbonate;bis(tri-t-butylphosphine)palladium(0); In 1,4-dioxane; water; at 120℃; for 1h;microwave irradiation;	A mixture of isopropyl 4-((lr,4r)-4-(6-bromo-2-methylpyridin-3- yloxy)cyclohexyloxy)piperidine-l-carboxylate (see Example 1.103, 125 mg, 0.274 mmol), pyrimidin-5-ylboronic acid (60.2 mg, 0.486 mmol), cesium carbonate (178 mg, 0.546 mmol), and bis(tri-t-butylphosphine)palladium(0) (5 mg, 9.78 muiotaetaomicron) in 4.5 mL dioxane/water (10: 1) was heated under microwave irradiation at 120 C for 1 h. The mixture was partitioned between water and EtOAc. The aqueous phase was removed. The organic phase was dried over MgS04, filtered, and concentrated. Residue was purified by Biotage flash chromatography (Si02, hexane/EtOAc) to give isopropyl 4-((lr,4r)-4-(2-methyl-6-(pyrimidin-5-yl)pyridin-3- yloxy)cyclohexyloxy)piperidine-l-carboxylate (69.2 mg, 0.152 mmol, 55.5% yield) as a white solid. Exact mass calculated for C25H34N4O4: 454.26, found: LCMS mlz = 455.2 [M+H]+; lU NMR (400 MHz, CDC13) delta 1.23 (d, J = 6.3 Hz, 6H), 1.48-1.67 (m, 6H), 1.77-1.81 (m, 2H), 1.96-2.01 (m, 2H), 2.10-2.15 (m, 2H), 2.54 (s, 3H), 3.12-3.19 (m , 2H), 3.56-3.60 (m, 2H), 3.79- 3.82 (m, 2H), 4.37-4.39 (m, 1H), 4.90-4.94 (m, 1H), 7.18 (d, J = 8.6 Hz, 1H), 7.53 (d, J = 8.6 Hz, 1H), 9.18 (s, 1H), 9.26 (s, 2H).

Reference： [1]Patent: WO2011/127051,2011,A1 .Location in patent: Page/Page column 196

60
1-(3-bromophenyl)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1H-isoindol-3-amine hemifumarate [ No CAS ]
[ 109299-78-7 ]
[ 1227164-02-4 ]
[ 1227163-84-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;3-(di-tert-butylphosphino)-propane-1-sulfonic acid; palladium diacetate; In water; butan-1-ol; at 80.0℃;Inert atmosphere;	Example 5; (1S)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine; Inert atmosphere (nitrogen) was used throughout the reaction. 1-(3-bromophenyl)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1H-isoindol-3-amine hemifumarate (1.51 g, 2.66 mmol) and 5-pyrimidineboronic acid (0.43 g, 2.92 mmol) were dissolved in n-butanol (10.5 mL). Aqueous potassium carbonate (K2CO3, 1.64 g, 11.9 mmol in 4.5 mL water) was added, then 3-(di-tert-butylphosphonium)propane sulfonate (DTBPPS, 7.4 mg, 0.027 mmol) and palladium(II) diacetate (6.2 mg, 0.028 mmol). The formed two phase system was heated to 80 C. (bath) over 30 minutes, and then stirred at this temperature over night (it had completed after approximately 3 h). The reaction mixture was cooled to 50 C. over 30 min. n-Butanol (4 mL) was added. The lower aqueous phase was separated off and the organic layer washed with brine (10% w/w, 7 mL). The organic phase was filtered through a PALL syringe filter (0.8 mum) which was rinsed with n-butanol (4 mL). The collected organic phase was distilled to a final weight of 13.75 g with solid material present. This was heated in 90 C. and stirred for approximately 1 hour then the heating was switched off and the mixture slowly cooled in the bath. The mixture was then cooled on an ice-bath for approximately 1 hour. The solids were filtered off, washed with cool 1-butanol (2*5 mL) and dried to give 0.32 g 28% of a racemic mixture of the title compound. The mother liquors, 17.65 g n-butanol solution contained 3.8% w/w equivalent to 0.671 g (59% yield) of the title compound with an enantiomeric excess of 93.6% (3.2% opposite enantiomer).

Reference： [1]Patent: US2011/281894,2011,A1 .Location in patent: Page/Page column 11

61
trans-rac-5-(5-bromo-2,4-difluorophenyl)-6-fluoro-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine [ No CAS ]
[ 109299-78-7 ]
(RS,RS)-5-(2,4-difluoro-5-pyrimidin-5-ylphenyl)-6-fluoro-5-methyl-5,6-dihydro-2H-1,4-oxazin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere;	Intermediate 39 (0.25 g, 0.774 mmol), 5-pyrimidinylboronic acid (0.143 g, 1.16 mmol) and tetrakis(triphenylphosphine) palladium(O) (0.089 g, 0.077 mmol) were dissolved in a mixture of 1 ,4-dioxane (11 mL) and aqueous NaHC03 (sat. sol, 7.5 mL). The resulting mixture was flushed with N2 and then heated at 80 C for 2 hours. The reaction mixture was then diluted with water and then extracted with DCM. The organic layer was separated, dried (Na2S04), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; 7 M solution of ammonia in methanol/DCM 0/100 to 10/90). The desired fractions were collected and concentrated in vacuo to yield compound 83 (0.18 g, 72%). This racemic compound was then purified by preparative SFC on Chiralpak Diacel AD (30 x 250 mm), mobile phase (C02, iPrOH with 0.2% iPrNH2), yielding compound 82 and compound 148 (0.050 g, 20% yield) as pure enantiomers (both as solid compounds).

Reference： [1]Patent: WO2011/154431,2011,A1 .Location in patent: Page/Page column 117

62
7-tert-butoxycarbonyl-2-exo-(2'-amino-3'-bromo-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane [ No CAS ]
[ 109299-78-7 ]
7-tert-butoxycarbonyl-2-exo-[2'-amino-3'-(pyrimidin-3-yl)-5'-pyridinyl]-7-azabicyclo[2.2.1]-heptane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 100℃; for 24h;Inert atmosphere;	To a resealable reaction pressure vessel under nitrogen was added 7 (827, 2.25 mmol, 1.0 equiv), Pd(PPh3)4 (130, 0.1 12 mmol, 5 mol %), Na2C03 (476 mg, 4.49 mmol, 2.0 equiv), pyrimidine boronic acid (362 mg, 2.92 mmol, 1.3 equiv), DME (12 mL), and water (1.5 mL). The mixture was degassed through bubbling nitrogen for 40 min and heated at 100 C for 24 h. After cooling to room temperature the mixture was poured into 30 mL of H20 and extracted with CHC13 (3 x 40 mL). The combined organic layers were dried over MgS04, filtered through Celite and the solvent removed in vacuo. The resultant residue was purified by flash chromatography using hexanes/EtOAc to furnish 585 mg (71%) of 66 as yellowish oil. lR NMR (300 MHz, CDC13) delta 1.44 (br s, 9H), 1.49-1.62 (m, 3H), 1.81-1.85 (m, 3H), 1.95-2.02 (m, 1H), 2.80-2.84 (dd, J= 9.0 Hz, 1H), 4.16 (s, 1H), 4.35 (br s, 1H), 7.37 (d, J= 1.7 Hz, 1H), 8.01 (d, J= 2.0 Hz, 1H) 8.86 (s, 2H), 9.18 (s, 1H); 13C NMR (CDC13) delta; 28.2 (3 C), 28.7, 29.6, 40.2, 44.7, 55.8, 62.1, 79.5, 114.3, 132.1, 132.4, 137.0, 147.5, 154.6, 154.9, 156.6, 157.5; MS (ESI) Jz 368.4 (M+H)+.

Reference： [1]Patent: WO2012/24615,2012,A1 .Location in patent: Page/Page column 75

63
7-tert-butoxycarbonyl-2-exo-(3'-bromo-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane [ No CAS ]
[ 109299-78-7 ]
7-tert-butoxycarbonyl-2-exo-[3'-(pyrimidin-5-yl)-5'-pyridinyl]-7-azabicyclo[2.2.1]heptane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 100℃; for 24h;Inert atmosphere;	To a resealable reaction pressure vessel under nitrogen was added 48 (316 mg, 0.895 mmol, 1 .0 equiv), Pd(PPh3)4 (52 mg, 0.045 mmol, 0.1 equiv), Na2C03 (190 mg, 1.79 mmol, 2.0 equiv), pyrimidine boronic acid (144 mg, 1.16 mmol, 1.3 equiv), DME (16 mL), and water (1.5 mL). The mixture was degassed through bubbling nitrogen for 40 min and heated at 100 C for 24 h. After cooling to room temperature the mixture was poured into 30 mL of H20 and extracted with CHC13 (3 x 40 mL). The combined organic layers were dried over MgS04, filtered through Celite and the solvent removed in vacuo. The resultant residue was purified by flash chromatography using hexanes/EtOAc to furnish 285 mg (90%) of 69 as a colorless oil. 1H NMR (300 MHz, CDC13) delta 1.44 (br s, 9H), 1.58-1.69 (m, 3H), 1.87-1.94 (m, 3H), 2.05-2.12 (m, 1H), 2.99-3.04 (dd, J = 9.0 Hz, 1H), 4.30 (s, 1H), 4.43 (br s, 1H), 7.91 (t, J= 1.9 Hz, 1H), 8.61 (d, J= 1.7 Hz, 1H), 8.70 (d, J= 2.0 Hz, 1H) 8.98 (s, 2H), 9.27 (s, 1H); 13C NMR (CDC13) delta; 28.4 (3 C), 29.0, 29.8, 40.6, 45.5, 56.2, 61.9, 80.1, 130.1 , 131.7, 132.7, 141.9, 145.9, 149.7, 155.2, 158.2; MS (ESI) m/z 353.5 (M+H)+.

Reference： [1]Patent: WO2012/24615,2012,A1 .Location in patent: Page/Page column 77

64
[ 1369543-18-9 ]
[ 109299-78-7 ]
[ 1369543-19-0 ]

Yield	Reaction Conditions	Operation in experiment
59%	With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In ethanol; toluene; at 20 - 150℃; for 0.5h;Inert atmosphere; Microwave irradiation;	Example A27Preparation of intermediate 27: rac-4-methyl-4-(3-pyrimidin-5-ylphenyl)-4,5- dihydropyrazolo\|"L5-a"\|pyrazin-6-onePalladium(II) acetate (0.017 g, 0.075 mmol) was added to a stirred suspension of rac-4- (3-chloro-phenyl)-4-methyl-4,5-dihydro-pyrazolo[l,5-a]pyrazin-6-one (0.13 g, 0.50 mmol), pyrimidine-5-boronic acid (0.19 g, 1.49 mmol), 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl (0.061 g, 0.149 mmol) and potassium phosphate (0.21 g, 0.99 mmol) in toluene (5 mL) and EtOH (0.5 mL) at room temperature and under nitrogen. The mixture was stirred at 150 C for 30 minutes under microwave irradiation. Then the mixture was filtered through diatomaceous earth and washed with AcOEt. The filtrate was evaporated in vacuo. The residue was purified by flash columnchromatography (silica gel; AcOEt). The desired fractions were collected and concentrated in vacuo to yield rac-4-methyl-4-(3-pyrimidin-5-yl-phenyl)-4,5-dihydro- pyrazolo[l,5-a]pyrazin-6-one (0.09 g, 59% yield) as a white solid.
59%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In ethanol; toluene; at 20 - 150℃; for 0.5h;Inert atmosphere; Microwave irradiation;	Palladium(II) acetate (0.017 g, 0.075 mmol) was added to a stirred suspension of rac-4-(3-chloro-phenyl)-4-methyl-4,5-dihydro-pyrazolo[1,5-a]pyrazin-6-one (0.13 g, 0.50 mmol), pyrimidine-5-boronic acid (0.19 g, 1.49 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.061 g, 0.149 mmol) and potassium phosphate (0.21 g, 0.99 mmol) in toluene (5 mL) and EtOH (0.5 mL) at room temperature and under nitrogen. The mixture was stirred at 150 C. for 30 minutes under microwave irradiation. Then the mixture was filtered through diatomaceous earth and washed with AcOEt. The filtrate was evaporated in vacuo. The residue was purified by flash column chromatography (silica gel; AcOEt). The desired fractions were collected and concentrated in vacuo to yield rac-4-methyl-4-(3-pyrimidin-5-yl-phenyl)-4,5-dihydro-pyrazolo[1,5-a]pyrazin-6-one (0.09 g, 59% yield) as a white solid.

Reference： [1]Patent: WO2012/38438,2012,A1 .Location in patent: Page/Page column 36-37
[2]Patent: US2013/190318,2013,A1 .Location in patent: Paragraph 0119; 0120

65
[ 1246350-28-6 ]
[ 109299-78-7 ]
[ 1367874-87-0 ]

Yield	Reaction Conditions	Operation in experiment
66%	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,3-dioxane; at 90℃; for 18h;Inert atmosphere;	Example 334-( Cyclohexyloxy)-3-(pyrimidin-5-yl)- 1 H-pyrazolo[4, 3-c]pyridine Step 14-(Cyclohexyloxy)-3-(pyrimidin-5-yl -1-trityl-1H-pyrazolo[4^-^^Intermediate 11 (120 mg, 0.21 mmol), Pd(dppf)CI2 (16 mg, 0.02 mmol), 2M Na2C03 (aq) (358 muIota, 0.72 mmol) and pyrimidine-5-boronic acid (38 mg, 0.31 mmol) were combined in dioxane (1 ml) and the solution degassed with nitrogen. The vial was then flushed out with nitrogen and heated at 90 C for 18 h. The solution was partitioned between DCM and water and filtered through a phase separator cartridge. The solvents were evaporated and the crude material purified by column chromatography gradient elution from 10-100% ethyl acetate / petroleum ether to give a white solid (73 mg, 66%). 1H NMR (400 MHz, DMSO-dB) delta ppm 1.22 - 1.45 (m, 3 H), 1.45 - 1.59 (m, 3 H), 1.59 - 1.69 (m, 2 H), 1.93 - 2.02 (m, 2 H), 5.25 (m, 1 H), 5.90 (d, J=6.0 Hz, 1 H), 7.13 - 7.26 (m, 6 H), 7.26 - 7.42 (m, 10 H), 7.64 (d, J=6.4 Hz, 1 H), 9.21 (s, 2 H); Rf = 0.67 (1 :1 , petroleum ether : ethyl acetate).

Reference： [1]Patent: WO2012/38743,2012,A1 .Location in patent: Page/Page column 120-121

66
[ 1374208-34-0 ]
[ 109299-78-7 ]
[ 1374208-35-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 95℃; for 2.16667h;Inert atmosphere;	Step 7: 2-Chloro-4-morpholin- -yl-7-pyrimidin-5-yl-quinazolineTo a 50 mL round bottom flask, 7-bromo-2-chloro-4-morpholin-4-yl-quinazoline (0.2 g, 0.0006 mol), pyrimidine-5-boronic acid (0.068 g, 0.0005 mol), sodium carbonate (0.129 g, 0.0012 mol), DMF (10 mL) and water (3 mL) were added and degassed the reaction vessel with N2 for 5-10 min. To the same reaction mixture, Pd(PPh3)2Cl2 (0.029 g, 0.00004 mol) was added and again degassed with N2 for 5-10 min. The reaction mixture was stirred at 95C for 2 h. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified; using column chromatography (60-120 silica gel, 60% ethyl acetate in hexane) to yield the desired product [ 150 mg, 75%] . 1H NMR (300 MHz,CDCI3): delta 9.27 (s, 1H), 9.04 (s, 2H), 7.85-8.45 (m, 2H), 7.60-7.64 (m, 1H), 3.82-3.91 (m, 8H); LC-MS (ESI): Calculated mass: 327.09; Observed mass: 328.0 [M+H]+ (RT: 0.98 min).

Reference： [1]Patent: WO2012/58671,2012,A1 .Location in patent: Page/Page column 93-94

67
[ 1374208-45-3 ]
[ 109299-78-7 ]
[ 1374208-46-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 95℃; for 2.16667h;Inert atmosphere;	Step 7: 2-Chloro-6-fluoro-4-morpholin-4-yl-7-pyridin-3-yl-quinazolineTo a 50 mL round bottom flask, 7-bromo-2-chloro-6-fluoro-4-morpholin-4-yl- quinazoline (200 mg, 0.0005764 mol), pyridine-3-boronic acid (63.3 mg, 0.0005188 mol), sodium carbonate (152.6 mg, 0.001441 mol), DMF (10 mL) and water (5 mL) were added and degassed the reaction vessel with nitrogen for 5-10 min. To the same reaction mixture, Pd(PPh3)2Cl2 (20.1 mg, 0.0000288 mol) was added and again degassed with N2 for 5-10 min. The reaction mixture was stirred at 95C for 2 h. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified using column chromatography (60-120 silica gel, 2% MeOH in chloroform) to yield the desired product (180 mg, 91%). 1H NMR (300 MHz, CD3OD): delta 8.27-8.30 (m, 1H), 8.21-8.25 (m, 1H), 8.15-8.18 (m, 1H), 7.91-7.92 (m, 1H), 7.74-7.78 (m, 1H), 7.47-7.51 (m, 1H), 3.99-4.01 (m, 4H), 3.85-3.88 (m, 4H); LC-MS (ESI): Calculated mass: 344.1; Observed mass: 344.9 [M+H]+ (RT: 1.3 min).

Reference： [1]Patent: WO2012/58671,2012,A1 .Location in patent: Page/Page column 104

68
[ 473416-91-0 ]
[ 109299-78-7 ]
[ 1415208-99-9 ]

Yield	Reaction Conditions	Operation in experiment
51%	With caesium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 100℃; for 0.75h;	Preparation 152,4-difluoro-5-(pyrimidin-5-yl)benzaldehydeA mixture of bis(triphenylphosphine)palladium(II) chloride (0.56 g, 0.80 mmol), pyrimidin-5-ylboronic acid (0.99 g, 8.0 mmol), <strong>[473416-91-0]5-bromo-2,4-difluorobenzaldehyde</strong> (0.88 g, 3.98 mmol), cesium carbonate (2.59g, 7.96 mmol) in DME (13 mL), EtOH (7 mL) and water (7 mL) was heated at 100 C for 45 min, and the crude reaction mixture was subjected to HPLC separation eluting with 0-100% A/B (A: 95% H20/5% MeCN, 10MM NH4OAc; B: 5% H20/95% MeCN, 10 mM NH4OAC over 30 min period to give the title compound as a white solid (450 mg, 51% yield). ¾ NMR (500 MHz,CHLOROFORM-d) delta 10.40 - 10.33 (m, IH), 9.28 (s, IH), 8.94 (d, J=1.2 Hz, 2H), 8.06 (dd, J=8.4, 7.8 Hz, IH), 7.15 (t, J=9.9 Hz, IH), 10.37 (s, IH).
51%	With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 100℃; for 0.75h;	Preparation 3 2,4-difluoro-5-(pyrimidin-5-yl)benzaldehyde A mixture of bis(triphenylphosphine)palladium(II) chloride (0.56 g, 0.80 mmol), pyrimidin-5-ylboronic acid (0.99 g, 8.0 mmol), <strong>[473416-91-0]5-bromo-2,4-difluorobenzaldehyde</strong> (0.88 g, 3.98 mmol), cesium carbonate (2.59g, 7.96 mmol) in DME (13 mL), EtOH (7 mL) and water (7 mL) was heated at 100 C for 45 min, and the crude reaction mixture was subjected to HPLC separation eluting with 0-100% A/B (A: 95% H20/5% MeCN, 10 MM NH4OAc; B: 5% H20/95% MeCN, 10 mM NH4OAC over 30 min period to give the title compound as a white solid (450 mg, 51% yield). *H NMR (500 MHz, CHLOROFORM-d) delta 10.40 - 10.33 (m, 1H), 9.28 (s, 1H), 8.94 (d, J=1.2 Hz, 2H), 8.06 (dd, J=8.4, 7.8 Hz, 1H), 7.15 (t, J=9.9 Hz, 1H), 10.37 (s, 1H).

Reference： [1]Patent: WO2012/162334,2012,A1 .Location in patent: Page/Page column 39
[2]Patent: WO2014/98831,2014,A1 .Location in patent: Page/Page column 27; 28

69
[ 190273-89-3 ]
[ 109299-78-7 ]
[ 1425503-95-2 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1996 - 2015

70
[ 669066-35-7 ]
[ 109299-78-7 ]
[ 1428882-00-1 ]

Yield	Reaction Conditions	Operation in experiment
68.2%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 85℃; for 17h;Inert atmosphere;	Preparation 92A: 3-Fluoro-4-(p rimidin-5-yl)picolinonitrile[00317] A vial containing a mixture of <strong>[669066-35-7]3-fluoro-4-iodopicolinonitrile</strong> (1.25 g, 5.04 mmol), pyrimidin-5-ylboronic acid (1.249 g, 10.08 mmol), and cesium carbonate (3.45 g, 10.58 mmol) in dioxane (Ratio: 2.0, Volume: 10.18 ml) and water (Ratio: 1.000, Volume: 5.09 ml) was degassed with N2 for 5 min, then PdCl2(dppf)-CH2Cl2Adduct (0.218 g, 0.267 mmol) was added. The solution was heated at 85 C for 17 hr, and then allowed to cool to room temperature. The reaction was quenched with water. The reaction mixture was diluted with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3X). The organic phases were combined, dried over Na2S04, filtered, and concentrated to afford a brown residue. The crude material was purified by MPLC (80 g column, 60 mL/min, 30-100% EtOAc in hexanes) to give the title compound (695 mg, 3.44 mmol, 68.2% yield) as a pink solid. ESI MS (M+H)+ = 201.1.

Reference： [1]Patent: WO2013/49263,2013,A1 .Location in patent: Paragraph 00316; 00317

71
[ 45762-41-2 ]
[ 109299-78-7 ]
[ 1449516-27-1 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 95℃; for 24h;Inert atmosphere;	<strong>[45762-41-2]4-Bromo-2-ethylaniline</strong> (0.5 g, 2.5 mmol), boronic acid or boronate pinacol ester (1.2 equiv., 3 mmol) and cesium carbonate (2.4 g, 7.5 mmol) are suspended in 1,4-dioxane (10 mL) and water (2 rriL) and the reaction mixture is then degassed (N2) fo r 5 min . A ft er wh ic h [ 1 , Gamma- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.102 g, 0.125 mmol) is added and the reaction mixture is heated to 95C for 1 d. The reaction is cooled to room temperature and filtered through Celite, washed through with DCM and the organics are washed with water, the layers are separated and the aqueous layer further extracted with DCM. The organics are combined, dried (hydrophobic filter) and concentrated in vacuo. The resulting residue is dissolved in DCM and allowed to load under gravity onto a 10 g SCX column, washed with DCM and MeOH and eluted with 7 N NH3 in MeOH : MeOH (1 :5). The eluent is concentrated in vacuo and the resulting residue is purified using column chromatography on silica gel. The fractions containing product are combined and concentrated in vacuo to give 4-Aryl-2-Ethylaniline.

Reference： [1]Patent: WO2013/117649,2013,A1 .Location in patent: Paragraph 00281

72
[ 109299-78-7 ]
[ 290368-00-2 ]
C₁₁H₈N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 120℃; for 1h;Microwave irradiation;	General procedure: <strong>[290368-00-2]ter<strong>[290368-00-2]t-butyl 3-iodo-1H-indazole-1-carboxylate</strong></strong> (S2, 100 mg, 0.29 mmol) was placed in a microwave vial and dissolved in 1,4-dioxane (11.5 mL). 3-Methoxyphenylboronic acid (88 mg, 0.58 mmol, 2.0 equiv) and tetrakis(triphenylphosphine)palladium (20 mg, 0.017 mmol, 0.06 equiv) were added, and the resulting mixture was sparged thoroughly with nitrogen. An aqueous solution of sodium carbonate (2.0 M, 0.65 mL, 1.3 mmol, 4.5 equiv) was then added. The biphasic mixture was microwaved for 1 hour at a reaction temperature of 120 C. After cooling to room temperature, the reaction was diluted with ethyl acetate (2 mL), and then filtered through a celite pad with additional ethyl acetate. The filtrate was concentrated under reduced pressure to give an oil. The crude material was purified by column chromatography over silica gel (hexanes/ethyl acetate: 100/0 to 30/70) to give the title compound as an oil (58.0 mg, 89%).

Reference： [1]Beilstein Journal of Organic Chemistry,2013,vol. 9,p. 1501 - 1507

73
[ 5788-58-9 ]
[ 109299-78-7 ]
[ 1549708-49-7 ]

Yield	Reaction Conditions	Operation in experiment
9.993 g	With pyridine; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(II) acetate monohydrate; In dichloromethane; at 20℃;Molecular sieve; Inert atmosphere;	Following a published method,27 28 (10.123g, 39.87mmol, 1.00 equiv), pyrimidine-5-boronic acid (37) (24.90g, 200.97mmol, 5.40 equiv), TEMPO (18.50g, 118.40mmol, 2.97 equiv), Cu(OAc)2·H2O (4.20g, 21.04mmol, 0.53 equiv) and powdered 4A molecular sieves (6.7g) were combined in CH2Cl2 (300mL). To this mixture was added pyridine (3.40mL, 42.21mmol, 1.06 equiv), and the resulting khaki suspension was stirred vigorously at 20C under N2 for 15min, and then under atmospheric air (via three needles in one of the septa capping the reaction vessel). A further quantity of pyridine (15.00mL, 186.22mmol, 4.67 equiv) was then added, causing an immediate change in the colour of the reaction mixture to a blue suspension, which became a green suspension after stirring overnight. The rate of stirring was decreased and the mixture was stirred at 20C for 8.5days. The reaction was then filtered through a pad of Celite, and the filtrate was diluted, washed with saturated aqueous NaOAc, and extracted with CH2Cl2 (×4). The combined organic extracts were washed (saturated aqueous NaHCO3, dried, and concentrated to dryness under reduced pressure. The resulting viscous red semi-solid was triturated with 20% EtOAc/hexanes to give 40 (9.993g) as a ?1:1 mixture with an unidentified impurity (probably starting material judged by 1H NMR), and was used without further purification: 1H NMR (CDCl3): 10.77 (v br s, 1H), 9.23 (s, 1H), 9.16 (s, 2H), 8.03 (s, 1H), 7.84 (s, 1H); HRESIMS calcd for C8H581Br2N4O m/z [M+H]+ 334.8784, found 334.8801, calcd for C8H581Br79BrN4O m/z [M+H]+ 332.8804, found 332.8820, calcd for C8H579Br2N4O m/z [M+H]+ 330.8825, found 330.8832; TLC Rf=0.18, 0.20 (20% EtOAc/hexanes).

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1029 - 1039

74
[ 109299-78-7 ]
[ 290368-00-2 ]
C₁₆H₁₆N₄O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 1327 - 1333

75
[ 552331-06-3 ]
[ 109299-78-7 ]
[ 1578483-82-5 ]

Yield	Reaction Conditions	Operation in experiment
42%	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 150℃; for 0.5h;Microwave irradiation;	3-Chloro-6-(pyrimidin-5-yl)isoquinoline Method E A suspension of <strong>[552331-06-3]6-bromo-3-chloroisoquinoline</strong> (62 mg, 0.27 mmol), pyrimidin-5- ylboronic acid (45 mg, 0.36 mmol), Pd(PPh3)4 (29.5 mg, 0.026 mmol) and CsF (1 17 mg, 0.77 mmol) in DME/MeOH (3/1 mL) was stirred at 150 X1 under microwave irradiation for 30 minutes. The reaction mixture was filtered and concentrated in vacuo. The residue was purified using Biotage silica gel column chromatography eluting with between 20- 60% EtOAc in cyclohexane to afford the title compound (26 mg, 42%). 1 H NMR (500 MHz, CDCI3): delta 9.32 (s, 1 H), 9.17 (s, 1 H), 9.09 (s, 2H), 8.16 (dt, J = 8.5, 0.9 Hz, 1 H), 7.98 (dd, J = 1 .8, 0.9 Hz, 1 H), 7.88 - 7.78 (m, 2H). LCMS (ESI) Rt = 2.14 minutes MS m/z 242 [M+H]+

Reference： [1]Patent: WO2014/37751,2014,A1 .Location in patent: Paragraph 00257-00259

76
[ 923595-49-7 ]
[ 109299-78-7 ]
[ 1580454-41-6 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2789 - 2798

77
[ 1161009-88-6 ]
[ 109299-78-7 ]
5-(9,9'-spirobi[fluoren]-4-yl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In N,N-dimethyl-formamide; at 150℃;	General procedure: 9,9'-Spirobi[fluorene] brominated compound, boronic acid compound, K2CO3 and Pd(dppf)Cl2 were dissolved in dry DMF or xylenes. The mixture was warmed to 150 C (DMF) and 135 C (xylenes) stirred overnight. After cooling to room temperature, saturated solution of ammonium chloride (50 mL) was added, and organic layer was extracted three times with dichloromethane (3x30 mL) and washed with brine (3x30 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Teledyne Isco CombiFlash Rf 400. Column conditions can be found in each compounds description below.

Reference： [1]Tetrahedron,2015,vol. 70,p. 6337 - 6351

78
[ 75-05-8 ]
[ 109299-78-7 ]
[ 40805-79-6 ]

Reference： [1]Chemistry - A European Journal,2015,vol. 21,p. 13246 - 13252

79
[ 890148-78-4 ]
[ 109299-78-7 ]
2,4,6-tris(3-(pyrimidin-5-yl)phenyl)-1,3,5-triazine [ No CAS ]

Reference： [1]Journal of Materials Chemistry C,2016,vol. 4,p. 1482 - 1489

80
[ 51839-15-7 ]
[ 109299-78-7 ]
C₁₄H₁₂N₂O₄ [ No CAS ]

Reference： [1]Applied Organometallic Chemistry,2019,vol. 33

81
[ 21193-80-6 ]
[ 109299-78-7 ]
4-amino-5-(pyrimidin-5-yl)-N7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; at 20 - 100℃; for 38.0h;Inert atmosphere;	(0.17 g, 0.50 mmol, 1 eq.), pyrimidin-5-yl-boronic acid (0.092 g, 0.75 mmol, 1.5 eq.), Pd2(dba)3 (0.005 g,0.005 mmol, 0.01 eq.) and P(c-hexyl)3 (0.0035 g, 0.012 mmol, 0.024eq.) were added to a 10mL round-bottom flask containing a stir bar.Next, the flask was evacuated and refilled with argon three times.Then, 1,4-dioxane was added (1.33 mL, 2.67 mL/mmol SM) togetherwith 1.27M aq. K3PO4 solution (0.67 mL, 1.3 mL/mmol). The flaskwas stirred at ambient temperature for ~5 min and then transferred to a pre-heated oil bath at 100 C. Heating was continued for 38 h,after which the mixture was cooled to ambient temperature. Themixture was neutralized (pH ~ 7) with 0.5M aq. HCl. The mixturewas evaporated till dryness re-suspended in MeOH and evaporated(three times). Next, the mixture was adsorbed onto Celite (fromMeOH) and eluted over a short silica pad (~5 cm) with 20% MeOH/DCM. The liquid was evaporated in vacuo and purified by columnchromatography 5/20% MeOH/EA. 18 was isolated as a yellowsolid (0.045 g, 0.13 mmol). Yield 26%. Melting point: 275 C(decomposed). 1H NMR (300 MHz, DMSO-d6) delta: 3.50-3.57 (m, 1H,H-5??), 3.60-3.67 (m, 1H, H-5'), 3.91 (q, J 3.6 Hz, 1H, H-4'),4.09-4.14 (m, 1H, H-3'), 4.45 (dd, J 11.1, 5.7 Hz, 1H, H-2'),5.14-5.18 (m, 2H, OH-3' , OH-5'), 5.36 (d, J 6.0 Hz, 1H, OH-2'), 6.13(d, J 6.0 Hz, 1H, H-1'), 6.51 (br. s, 2H, NH2), 7.77 (s, 1H, H-6), 8.18 (s,1H, H-2), 8.86 (s, 2H, H-4Pyrim, H-6Pyrim), 9.13 (s, 1H, H-2Pyrim). 13CNMR (75 MHz, DMSO-d6) delta: 61.6 (C-5'), 70.5 (C-3'), 73.8 (C-2'), 85.2(C-4'), 87.1 (C-1?), 100.3 (C-4a), 109.3 (C-5), 122.8 (C-6), 128.5 (C-5Pyrim), 151.4 (C-7a), 152.0 (C-2), 155.5 (2C, C-4Pyrim, C-6Pyrim), 156.2(C-2Pyrim), 157.6 (C-4). HRMS (ESI): calculated for C15H17N6O4([MH]): 345.1306, found: 345.1329.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 164,p. 689 - 705

82
[ 176967-80-9 ]
[ 109299-78-7 ]
8-nitro-5-(pyrimidin-5-yl)quinoline [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 1609 - 1625

83
[ 1111638-74-4 ]
[ 76513-69-4 ]
[ 104-94-9 ]
[ 109299-78-7 ]
C₂₄H₂₉N₇O₂Si [ No CAS ]
C₂₄H₂₉N₇O₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: A mixture of compound 4 (104.6 mg, 0.200 mmol), pyridine-3-boronic acid (52.1 mg, 0.424 mmol), Pd2(dba)3 (6.7 mg, 0.007 mmol), K3PO4 (198.2 mg, 0.934 mmol), H2O (0.5 mL), dioxane (0.5 mL), and 0.6 M tricyclohexylphosphine (20 muL,0.012 mmol) was refluxed under an argon atmosphere for 15 h. The reaction mixture was filtered, washed with EtOAc, and concentrated in vacuo. The residue was purified by column chromatography over silica gel (n-hexane-EtOAc) to give amixture of regioisomers 5a (40.2 mg, 43%) as a yellow oil. 1H-NMR (270 MHz, CDCl3, major peaks of regioisomers) delta: 8.86 (1H, d, J = 1.9 Hz), 8.62-8.64 (1H, m), 8.25 (1H, d,J = 5.4 Hz), 8.14 (1H, s), 7.88-7.91 (2H, m), 7.30-7.37 (2H, m), 7.10 (1H, s), 6.79-6.83 (2H, m), 6.56 (1H, d, J = 5.4 Hz), 5.51(2H, s), 3.80 (3H, s), 3.67-3.80 (2H, s), 0.91-1.01 (2H, m), 0.01 (9H, s). LC/MS (ESI): m/z 475 [M + H]+.

Reference： [1]Chemical and Pharmaceutical Bulletin,2019,vol. 67,p. 224 - 235

84
[ 1111638-74-4 ]
[ 76513-69-4 ]
[ 104-94-9 ]
[ 109299-78-7 ]
N-(4-methoxyphenyl)-4-(3-pyrimidin-5-yl-1H-pyrazol-4-yl)pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of compound 5a (40 mg, 0.084 mmol) in dry THF (6 mL) was added 1 M TBAF in THF (0.17 muL). The reaction mixture was refluxed for 3.5 h and added to brine, extracted with EtOAc, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography over silica gel (CH2Cl2-MeOH) to afford compound 6a (23.3 mg, 81%) as a yellow solid.

Reference： [1]Chemical and Pharmaceutical Bulletin,2019,vol. 67,p. 224 - 235

85
[ 39771-34-1 ]
[ 109299-78-7 ]
2,6-bis(pyrimidin-5-yl)pyridin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water;Inert atmosphere; Reflux;	Step 1: <strong>[39771-34-1]2,6-dibromo-4-aminopyridine</strong> (0.63 g, 2.50 mmol), pyrimidine-5-boronic acid (0.77 g, 6.25 mmol), 1,1'-bis(diphenylphosphino)ferrocenedichloropalladium(II) dichloromethane (0·1g, 0 · 13 mmol) and sodium carbonate (1.06 g, 0.01 mol) dispersed in 1,4-dioxane (40 mL) and water (20 mL) solution was stirred under reflux with nitrogen overnight. The reaction mixture was cooled to room temperature, concentrated to 30 mL under reduced pressure, and the obtained mixture was filtered, filtered, washed with water and dried in vacuo to give 2,6-bis(pyrimidin-5-yl)pyridin-4-amine (0.4 g, yield: 63%) is a gray solid.

Reference： [1]Patent: CN109651358,2019,A .Location in patent: Paragraph 0313; 0314

86
[ 76-09-5 ]
[ 109299-78-7 ]
[ 321724-19-0 ]

Reference： [1]Organic Letters,2019,vol. 21,p. 3048 - 3052

87
[ 1458-01-1 ]
[ 109299-78-7 ]
methyl 3,5-diamino-6-(pyrimidin-5-yl)pyrazine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; toluene;Inert atmosphere; Reflux;	General procedure: <strong>[1458-01-1]Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate</strong> 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29

88
[ 955368-90-8 ]
[ 109299-78-7 ]
C₁₃H₁₂N₆OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; oxygen; In dichloromethane; at 20 - 25℃; for 32h;	Copper acetate (81.72 mg, 449.90 mumol) and pyridine (284.70 mg, 3.60 mmol, 290.51 muL) were added into I1 (100.00 mg, 449.90 mumol) and 5-pyrimidinylboronic acid (111.49 mg, 899.80 mumol) in dichloromethane (10.00 mL) solution. Under oxygen atmosphere, the mixture was stirred at 20-25C for 32 hours, EtOAc (180 mL), washed by water 240 mL (120 mL ×2) and saturated brine 120 mL, dried over anhydrous sodium sulfate, then filtered and concentrated to give the crude compound 6-A, which was purified by thin phase chromatography (PE/EtOAc =2/1) to give compound 6-A. MS m/z: 300.9[M+H]+

Reference： [1]Patent: EP3572413,2019,A1 .Location in patent: Paragraph 0129-0131

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