[ CAS No. 720702-41-0 ] {[proInfo.proName]}

Name: 720702-41-0|(1-Methyl-1H-pyrazol-5-yl)boronic acid|95%
Brand: Ambeed
SKU: A201184
Price: 16.0 USD
Availability: InStock
Rating: 91 (35 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 720702-41-0 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 720702-41-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 720702-41-0 ]

SDS Specification

Alternatived Products of [ 720702-41-0 ]

Product Details of [ 720702-41-0 ]

CAS No. :	720702-41-0	MDL No. :	MFCD11053031
Formula :	C₄H₇BN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MGNBKNBEZGLHNF-UHFFFAOYSA-N
M.W :	125.92	Pubchem ID :	11182610
Synonyms :

Calculated chemistry of [ 720702-41-0 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.25
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	33.31
TPSA :	58.28 Å²

Pharmacokinetics

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

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	-0.83
Log Po/w (WLOGP) :	-1.9
Log Po/w (MLOGP) :	-1.79
Log Po/w (SILICOS-IT) :	-2.09
Consensus Log Po/w :	-1.32

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.44
Solubility :	45.4 mg/ml ; 0.361 mol/l
Class :	Very soluble
Log S (Ali) :	0.09
Solubility :	154.0 mg/ml ; 1.22 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	0.35
Solubility :	285.0 mg/ml ; 2.26 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.0

Safety of [ 720702-41-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 720702-41-0 ]

* 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 [ 720702-41-0 ]
Downstream synthetic route of [ 720702-41-0 ]

[ 720702-41-0 ] Synthesis Path-Upstream 1~4

1
[ 930-36-9 ]
[ 720702-41-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1.5 h; Stage #2: With Triisopropyl borate In tetrahydrofuran at -78 - 0℃; Stage #3: With hydrogenchloride; water In tetrahydrofuran	2-Methyl-2H-pyrazole-3-boronic acid: N-methyl pyrazole (25 mL, 0.3 mol) was dissolved in 500 mL of THF. The solution was then cooled to-78°C in a dry ice/isopropanol bath. Once the solution reached -78°C, n-BuLi (140 mL, 0.40 mol) was added dropwise by canula. The reaction mixture was stirred at -78°C for 1.5 hours. Then, triisopropyl borate (280 mL, 1.2 mol) was added to the above mixture via canula. While stirring overnight, the reaction temperature was gradually increased from -78δC to 0δC. The pH of the mixture was adjusted to 6 with IN HCI. THF was removed under reduced pressure, and the aqueous residue was extracted with EtOAc (2 x 100mL). The solid was then filtered to yield 108 g (100percent) of 2-methyl-2H-pyrazole-3-boronic acid as a yellow solid.

Reference： [1] Patent: WO2005/12254, 2005, A1, . Location in patent: Page/Page column 101
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 1923 - 1936
[3] Journal of Heterocyclic Chemistry, 2004, vol. 41, # 6, p. 931 - 939
[4] Patent: WO2004/58722, 2004, A1, . Location in patent: Page 63; 62

2
[ 930-36-9 ]
[ 5419-55-6 ]
[ 720702-41-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1.5 h; Stage #2: at 20℃;	Example 14-(Azetidin-1 -yl)-1 -methyl-3-[1 -methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-1H- pyrazolo[3,4-d]pyrimidine1Step 1: Synthesis of (1-methyl-1H-pyrazol-5-yl)boronic acid (C1) To a solution of 1 -methyl-1 /-/-pyrazole (1 10 g, 1 .34 mol) in anhydrous tetrahydrofuran (2 L), with stirring, was added drop-wise n-butyllithium (2.5 M, 590 imL, 1 .47 mol) at -78 °C. After completion of the addition, the mixture was stirred for 1 .5 hours at -78 °C. Then triisopropyl borate (277 g, 1 .47 mol) was added and the mixture was gradually warmed to room temperature and stirred overnight. Saturated aqueous ammonium chloride solution (1 L) was added drop- wise, while keeping the temperature of the reaction mixture below 10 °C. The resulting mixture was acidified to a pH of approximately 6 with 1 N aqueous hydrochloric acid. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (3 x 1 L). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, and filtered; and the solvent was removed under reduced pressure. The residue was washed with petroleum ether (3 x 300 mL) and the resulting solid was dried under vacuum to afford the product as a white solid. Yield: 157 g, 1.25 mol, 93percent. H NMR (400 MHz, DMSO-cf₆) δ 3.97 (s, 3H), 6.72-6.74 (m, 1 H), 7.34-7.36 (m, 1 H), 8.35 (br s, 2H).

Reference： [1] Patent: WO2012/168817, 2012, A1, . Location in patent: Page/Page column 44-45
[2] Patent: US2009/62269, 2009, A1, . Location in patent: Page/Page column 54

3
[ 930-36-9 ]
[ 121-43-7 ]
[ 720702-41-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; for 4 h; Stage #2: at -70℃;	A solution of 1-methylpyrazole (25.0 g, 305 mmol) in tetrahydrofuran (THF) (600 mL) was cooled to 0 °C. n-Butyl lithium (1.6 M in hexanes, 209 mL, 335 mmol) was added drop-wise over 1 h, keeping the temperature below 7 °C. The solution was stirred at room temperature (rt) for 3 h before cooling to −70 °C. B(OMe)₃ (44.4 mL, 0.40 mol) was slowly added, keeping the reaction temperature below −65 °C. The resulting mixture was allowed to warm to rt, before it was quenched with 15percent aqueous (aq) NH₄Cl (450 mL). The mixture was extracted with THF (3 × 500 mL), and the combined organic extracts were dried (Na₂SO₄) and evaporated in vacuo to give a yellowish solid (15.6 g, 41percent). The aq layer was concentrated in vacuo, and the resulting solid was repeatedly extracted with THF (5 × 250 mL). The combined organic extracts were dried (Na₂SO₄) and evaporated in vacuo, yielding a yellow solid (20.3 g, 52percent). The combined yield of (1-methyl-1H-pyrazol-5-yl)boronic acid was 35.9 g (93percent), and 20.3 g (161 mmol) of this material was esterified with pinacole (28.4 g, 240 mmol) in THF (200 mL). 4 Å molecular sieves (6.0 g dried in vacuo at 50 °C) were added, and the resulting mixture was stirred at rt for 2 days. The sieves were filtered off, and the filtrate was concentrated in vacuo. The resulting crude product was dissolved in heptane (500 mL) and washed with water (2 × 250 mL). The organic layer was dried (Na₂SO₄) and concentrated in vacuo to afford a white solid. This material was recrystallized from acetonitrile yielding white crystals (22.5 g, 67percent). Mp 71.0–71.6 °C (Ivachtchenko et al.,²¹ 74–76 °C). ¹H NMR (500 MHz, DMSO-d₆): δ, 7.46 (d, J = 1.9 Hz, pyrazole H-3), 6.62 (d, J = 1.9 Hz, pyrazole H-4), 3.98 (s, N-methyl), 1.30 (s, pinacol methyl groups, 12H). ¹³C NMR (126 MHz, DMSO-d₆): δ, 138.3, 115.9, 84.4 (2C), 41.9, 24.9 (4C). Anal. calcd for C₁₀H₁₇BN₂O₂: C, 57.73; H, 8.24; N, 13.46. Found: C, 57.72; H, 8.08; N, 13.40.

Reference： [1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 1, p. 196 - 204

4
[ 76-09-5 ]
[ 720702-41-0 ]
[ 847818-74-0 ]

Yield	Reaction Conditions	Operation in experiment
67%	at 20℃; for 48 h; Molecular sieve	A solution of 1-methylpyrazole (25.0 g, 305 mmol) in tetrahydrofuran (THF) (600 mL) was cooled to 0 °C. n-Butyl lithium (1.6 M in hexanes, 209 mL, 335 mmol) was added drop-wise over 1 h, keeping the temperature below 7 °C. The solution was stirred at room temperature (rt) for 3 h before cooling to −70 °C. B(OMe)3 (44.4 mL, 0.40 mol) was slowly added, keeping the reaction temperature below −65 °C. The resulting mixture was allowed to warm to rt, before it was quenched with 15percent aqueous (aq) NH4Cl (450 mL). The mixture was extracted with THF (3 × 500 mL), and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give a yellowish solid (15.6 g, 41percent). The aq layer was concentrated in vacuo, and the resulting solid was repeatedly extracted with THF (5 × 250 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo, yielding a yellow solid (20.3 g, 52percent). The combined yield of (1-methyl-1H-pyrazol-5-yl)boronic acid was 35.9 g (93percent), and 20.3 g (161 mmol) of this material was esterified with pinacole (28.4 g, 240 mmol) in THF (200 mL). 4 Å molecular sieves (6.0 g dried in vacuo at 50 °C) were added, and the resulting mixture was stirred at rt for 2 days. The sieves were filtered off, and the filtrate was concentrated in vacuo. The resulting crude product was dissolved in heptane (500 mL) and washed with water (2 × 250 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to afford a white solid. This material was recrystallized from acetonitrile yielding white crystals (22.5 g, 67percent). Mp 71.0–71.6 °C (Ivachtchenko et al.,21 74–76 °C). 1H NMR (500 MHz, DMSO-d6): δ, 7.46 (d, J = 1.9 Hz, pyrazole H-3), 6.62 (d, J = 1.9 Hz, pyrazole H-4), 3.98 (s, N-methyl), 1.30 (s, pinacol methyl groups, 12H). 13C NMR (126 MHz, DMSO-d6): δ, 138.3, 115.9, 84.4 (2C), 41.9, 24.9 (4C). Anal. calcd for C10H17BN2O2: C, 57.73; H, 8.24; N, 13.46. Found: C, 57.72; H, 8.08; N, 13.40.#10;

Reference： [1] Journal of Heterocyclic Chemistry, 2004, vol. 41, # 6, p. 931 - 939
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 1, p. 196 - 204

[ 720702-41-0 ] Synthesis Path-Downstream 1~82

1
[ 930-36-9 ]
[ 720702-41-0 ]

Yield	Reaction Conditions	Operation in experiment
100%		2-Methyl-2H-pyrazole-3-boronic acid: N-methyl pyrazole (25 mL, 0.3 mol) was dissolved in 500 mL of THF. The solution was then cooled to-78C in a dry ice/isopropanol bath. Once the solution reached -78C, n-BuLi (140 mL, 0.40 mol) was added dropwise by canula. The reaction mixture was stirred at -78C for 1.5 hours. Then, triisopropyl borate (280 mL, 1.2 mol) was added to the above mixture via canula. While stirring overnight, the reaction temperature was gradually increased from -78deltaC to 0deltaC. The pH of the mixture was adjusted to 6 with IN HCI. THF was removed under reduced pressure, and the aqueous residue was extracted with EtOAc (2 x 100mL). The solid was then filtered to yield 108 g (100%) of 2-methyl-2H-pyrazole-3-boronic acid as a yellow solid.
		To a stirred solution of 1-METHYLPYRAZOLE (19.80 g, 0.24 mol) in THF (500 ML) at-78 C was added N-BULI (2.5 M in hexane, 116 ML, 0.29 mol, 1.2 eq. ) slowly within 30 mins and the mixture was stirred at this temperature for an additional 1.5 hr. Triisopropyl borate (223.0 mL, 181.40 g, 0.96 mmol, 4.0 eq. ) was then added dropwise AT-78 C, followed by stirring overnight until it was warmed up to r. t.. The reaction mixture was acidified to pH = 6 with IN HCl, THF was removed under vacuum and the aqueous residue was extracted with EtOAc (5 X 400 mL). The combined organic phase was washed with brine, dried over anhydrous MgSO4, filtered and evaporated. The resultant white solid 2-methyl-2H-pyrazole-3-boronic acid was used without further purification in the subsequent Suzuki cross-coupling step: LCMS m/z (%) = 127 (MH+, 100). 'H NMR (400 MHz, CD30D) 8 : 7.38 (s, 1H), 6.57 (d, J= 4. 0 HZ, 1H), 3.81 (s, 3H).

Reference： [1]Patent: WO2005/12254,2005,A1 .Location in patent: Page/Page column 101
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 1923 - 1936
[3]Journal of Heterocyclic Chemistry,2004,vol. 41,p. 931 - 939
[4]Patent: WO2004/58722,2004,A1 .Location in patent: Page 63; 62

2
[ 76-09-5 ]
[ 720702-41-0 ]
[ 847818-74-0 ]

Yield	Reaction Conditions	Operation in experiment
67%	In tetrahydrofuran; at 20℃; for 48h;Molecular sieve;	A solution of 1-methylpyrazole (25.0 g, 305 mmol) in tetrahydrofuran (THF) (600 mL) was cooled to 0 C. n-Butyl lithium (1.6 M in hexanes, 209 mL, 335 mmol) was added drop-wise over 1 h, keeping the temperature below 7 C. The solution was stirred at room temperature (rt) for 3 h before cooling to -70 C. B(OMe)3 (44.4 mL, 0.40 mol) was slowly added, keeping the reaction temperature below -65 C. The resulting mixture was allowed to warm to rt, before it was quenched with 15% aqueous (aq) NH4Cl (450 mL). The mixture was extracted with THF (3 × 500 mL), and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give a yellowish solid (15.6 g, 41%). The aq layer was concentrated in vacuo, and the resulting solid was repeatedly extracted with THF (5 × 250 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo, yielding a yellow solid (20.3 g, 52%). The combined yield of <strong>[720702-41-0](1-methyl-1H-pyrazol-5-yl)boronic acid</strong> was 35.9 g (93%), and 20.3 g (161 mmol) of this material was esterified with pinacole (28.4 g, 240 mmol) in THF (200 mL). 4 A molecular sieves (6.0 g dried in vacuo at 50 C) were added, and the resulting mixture was stirred at rt for 2 days. The sieves were filtered off, and the filtrate was concentrated in vacuo. The resulting crude product was dissolved in heptane (500 mL) and washed with water (2 × 250 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to afford a white solid. This material was recrystallized from acetonitrile yielding white crystals (22.5 g, 67%). Mp 71.0-71.6 C (Ivachtchenko et al.,21 74-76 C). 1H NMR (500 MHz, DMSO-d6): delta, 7.46 (d, J = 1.9 Hz, pyrazole H-3), 6.62 (d, J = 1.9 Hz, pyrazole H-4), 3.98 (s, N-methyl), 1.30 (s, pinacol methyl groups, 12H). 13C NMR (126 MHz, DMSO-d6): delta, 138.3, 115.9, 84.4 (2C), 41.9, 24.9 (4C). Anal. calcd for C10H17BN2O2: C, 57.73; H, 8.24; N, 13.46. Found: C, 57.72; H, 8.08; N, 13.40.

Reference： [1]Journal of Heterocyclic Chemistry,2004,vol. 41,p. 931 - 939
[2]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 196 - 204

3
7-bromo-5-nitrobenzofuran [ No CAS ]
[ 720702-41-0 ]
[ 1010072-32-8 ]

Yield	Reaction Conditions	Operation in experiment
40%	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 85℃;	Example 1.1: Preparation of l-Methyl-5-(5-nitrobenzofuran-7-yl)-lH-pyrazoIe (Intermediate).; To a suspension of 7-bromo-5-nitrobenzofuran (1.747 g, 7.22 mmol), 1-methyl-lH- pyrazol-5-ylboronic acid (1.788 g, 14.2 mmol), and Cs2CO3 (7.86 g, 24.1 mmol) in dimethoxy ethane (DME; 125 mL) under argon was added Pd(PPh3)4 (372 mg, 0.322 mmol). The reaction mixture was heated to 85 0C overnight, cooled to room temperature, and then diluted with water (200 mL) and extracted with ethyl acetate (200 mL). The organic layer was dried with MgSO4 and concentrated in vacuo. The resulting residue was purified by silica gel chromatography to afford the title compound as a solid (708 mg, 40%). 1H NMR (400 MHz, CDCl3) delta: 8.61 (d, J= 2.27 Hz, IH), 8.28 (d, J= .T1 Hz, IH), 7.86 (d, J= 2.23 Hz, IH), 7.64 (d, J= 1.94 Hz, IH), 7.04 (, J= 2.23 Hz, IH), 6.60 (d, J= 1.95 Hz, IH), 3.94 (s, 3H).

Reference： [1]Patent: WO2008/27483,2008,A1 .Location in patent: Page/Page column 50

4
[ 839715-01-4 ]
[ 720702-41-0 ]
[ 839715-02-5 ]

Yield	Reaction Conditions	Operation in experiment
36.5%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In Dimethyl ether; water; at 20 - 80℃;	A 25-mL round-bottom flask was charged with (3-bromo-4-trifluoromethoxy-phenyl)-carbamic acid tert-butyl ester (230.0 mg, 0.65 mmol), 1-methyl pyrazole-5-boronic acid (392.9 mg, 1.93 mmol), sodium carbonate (137.8 mg, 1.3 mmol), DME (5 ml) and water (0.5 ml) under argon atmosphere. Tetrakis (triphenylphosphine) palladium (75.1 mg, 0.065 mmol) was added and reaction mixture purged with argon again. The reaction mixture was heated at 80C overnight then cooled to room temperature. Ethyl acetate (10 ml) was added then washed with brine and water. Organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give a residue that was subjected to a purification by flash chromatography (SiO2, Hexanes/EtOAc gradient elution) to afford [3-(2-methyl-2H-pyrazol-3-yl)-4-trifluormethoxy-phenyl]-carbamic acid tert-butyl ester as an off- white solid in 36.5% yield. LCMS m/z (%) = 358 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) delta: 9.83 (bs, 1H), 7.77 (d, J= 8.95 Hz, 1H), 7.69 (s, 1H), 7.63 (s, 1H), 7.57 (d, J= 8.84 Hz, 1H), 6. 45 (s, 1H), 3.78 (s, 3H), 1.60 (s, 9H).

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 1923 - 1936
[2]Patent: WO2005/12254,2005,A1 .Location in patent: Page/Page column 151-152

5
C₁₀H₁₉BN₂O₂ [ No CAS ]
[ 720702-41-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In tetrahydrofuran; water; pentane; for 0.5h;	To a solution of 1-methylpyrazole (820 mg, 10 mmol) in dry THF (20 mL) cooled to-70 C was added n-BuLi (1.6 M solution in hexane, 6.3 mL, 10 mmol) dropwise. The reaction mix was stirred at-70 C for 5 min, then triisopropyl borate (2.5 mL, 11 mmol) was added over 5 min. The mixture was allowed to warm to RT over 1 hr, then 6N hydrochloric acid (5 ml) was added. The mixture was stirred for 30 min, then was evaporated to dryness to provide crude 26a as a solid, which was used without further purification.

Reference： [1]Patent: WO2005/63755,2005,A1 .Location in patent: Page/Page column 74

6
[ 6276-04-6 ]
[ 720702-41-0 ]
[ 573711-79-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 70℃;	A mixture of 1-iodo-3, 5-dinitrobenzene (1.200g, 4.00 MMOL), 2-methyl-2H-pyrazole- 3-BORONIC ACID (90%, 1.679G, 10. OOMMOL, 3.0 EQ. ) AND NA2CO3 (6.783G, 64.00 MMOL, 16.0 eq. ) was dissolved in THF (100 mL) and H20 (75 mL). The mixture was degassed with N2 for 5 mins. Pd (PPH3) 4 (0.233g, 0.20 mmol, 0.05 eq. ) was then added, the solution was degassed for an additional 5 mins and the mixture was stirred at 70 C overnight. After consumption of the starting material, the reaction mixture was diluted with EtOAc (100mL), and the aqueous phase was extracted with EtOAc three times (3X 100 mL). The combined organic phase was washed with brine, dried over anhydrous MGS04, filtered and evaporated. The crude reaction mixture was purified by SiO2 column chromatography (Eluent: ETOAC/HEXANE = 1/3 then 1/1) providing 5-(3,5-dinitro-phenyl)-1-methyl-1H-pyrazole (0.937g, 3.78 mmol) in 90% yield: LCMS m/z (%) = 249 (MBF, 100). IN NMR (400 MHz, CDC13) 8 : 9.08 (t, J= 2.0 Hz, 1H), 8.63 (s, 1H), 8.62 (s, 1H), 7.61 (d, J= 2. 0 Hz, 1H), 6.55 (d, J = 1. 8 Hz, 1H), 4.01 (s, 3H)

Reference： [1]Patent: WO2004/58722,2004,A1 .Location in patent: Page 63; 62

7
[ 15862-50-7 ]
[ 720702-41-0 ]
[ 953396-70-8 ]

Yield	Reaction Conditions	Operation in experiment
31%	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 85℃;	Example 1.1: Preparation of Intermediate 2-Methoxy-3-(2-methyl-2H~pyrazol-3-yl)-5- nitro-pyridine.To a suspension of 3-bromo-2-methoxy-5-nitrorhoyridine (986 mg, 4.23 mmol), 1- methyl-lH-pyrazol-5-ylboronic acid (1.55 g, 12.3 mmol), and CsCO3 (5.24 g, 16.1 mmol) in DME (80 mL) under argon was added Pd(PPh3),, (269 mg, 0.233 mmol). The reaction mixture was heated to 85C overnight, cooled to room temperature, and then diluted with water (250 mL) and extracted with ethyl acetate (250 mL). The organic layer was dried with MgSO4 and <n="79"/>concentrated in vacuo. The resulting residue was purified by HPLC to afford 2-methoxy-3-(2- methyl-2H-pyrazol-3-yl)-5-nitro-pyridine as a beige solid (312 mg, 31%). LCMS m/z (%) = 235 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) delta: 9.20 (d, J= 2.76 Hz, IH), 8.47 (d, J= 2.76 Hz, IH), 7.53 (d, J= 1.90 Hz3 IH), 6.48 (d, J= 1.87 Hz, IH), 4.05 (s3 3H), 3.72 (s, 3H).

Reference： [1]Patent: WO2007/120600,2007,A2 .Location in patent: Page/Page column 75-76

8
[ 1085386-29-3 ]
[ 720702-41-0 ]
[ 1085386-27-1 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; at 70℃;	5-(2-Methvl-2H-pvrazol-3-vl)-2-(2A6-trimethvl-phenvlamino)-benzamide5-Bromo-2-(2,4,6-trimethyl-phenylamino)-benzamide (0.186 g, 0.56 mmol), 2-methyl-2H- pyrazole-3-boronic acid (0.141 g, 1.12 mmol), Cs2CO3 (0.459 g, 1 .39 mmol) and [1 ,1 '-bis- (diphenylphosphino)-ferrocene]dichloropalladium(ll) (0.023 g, 0.028 mmol) are placed into an oven-dried flask containing dimethoxyethane (2 ml_). The flask is closed with a septum. The reaction mixture is stirred at 709C overnight and then filtered. The filtrate is evaporated, and the residue is purified by flash-chromatography using hexane to hexane / ethyl acetate 7:3 as eluent to yield the crude product. Ethyl acetate is added, and the precipitate is filtered off and dried to yield 5-(2-methyl-2H-pyrazol-3-yl)-2-(2,4,6-trimethyl-phenylamino)-benzamide as a yellow solid. ESI-MS: 335.4 [M + H]+; rt = 5.08 min.

Reference： [1]Patent: WO2008/142073,2008,A1 .Location in patent: Page/Page column 19

9
[ 170011-47-9 ]
[ 720702-41-0 ]
[ 1057333-37-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 40℃; for 1h;	To a solution of the intermediate from step A (1.34 g, 1.2 equiv.) in 2:1 THF/2M Na2CO3 (75 mL total) was added the intermediate from example 6 step A (2.56 g, 1.0 equiv.). The resulting mixture was flushed with nitrogen and tetrakis triphenyl phosphine palladium (0) (513 mg, 5 mol %) was added. After stirring the reaction at 40 C. for 1 hour it was cooled to room temperature and neutralized with 1NHCl. The resulting mixture was extracted with EtOAc, washed with brine and dried over Na2SO4. The organic layer was filtered, concentrated in vacuo and purified by flash chromatography (silica-gel) using 1:1EtOAc/Hexto give a yellow oil.

Reference： [1]Patent: US2009/62269,2009,A1 .Location in patent: Page/Page column 54

10
[ 930-36-9 ]
[ 5419-55-6 ]
[ 720702-41-0 ]

Yield	Reaction Conditions	Operation in experiment
93%		Example 14-(Azetidin-1 -yl)-1 -methyl-3-[1 -methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-1H- pyrazolo[3,4-d]pyrimidine1Step 1: Synthesis of (1-methyl-1H-pyrazol-5-yl)boronic acid (C1) To a solution of 1 -methyl-1 /-/-pyrazole (1 10 g, 1 .34 mol) in anhydrous tetrahydrofuran (2 L), with stirring, was added drop-wise n-butyllithium (2.5 M, 590 imL, 1 .47 mol) at -78 C. After completion of the addition, the mixture was stirred for 1 .5 hours at -78 C. Then triisopropyl borate (277 g, 1 .47 mol) was added and the mixture was gradually warmed to room temperature and stirred overnight. Saturated aqueous ammonium chloride solution (1 L) was added drop- wise, while keeping the temperature of the reaction mixture below 10 C. The resulting mixture was acidified to a pH of approximately 6 with 1 N aqueous hydrochloric acid. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (3 x 1 L). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, and filtered; and the solvent was removed under reduced pressure. The residue was washed with petroleum ether (3 x 300 mL) and the resulting solid was dried under vacuum to afford the product as a white solid. Yield: 157 g, 1.25 mol, 93%. H NMR (400 MHz, DMSO-cf6) delta 3.97 (s, 3H), 6.72-6.74 (m, 1 H), 7.34-7.36 (m, 1 H), 8.35 (br s, 2H).
		To a solution of N-methylpyrazole (2.0 g, 24.4 mmol) in anhydrous THF (100 mL) cooled to -78 C. under a N2 atmosphere was added n-Butyl lithium (16.8 mL, 26.82 mmol, 1.6 M in hexanes). After 30 minutes, triisopropyl borate (6.75 mL, 29.27 mmol) was added. The reaction mixture was slowly warmed to 0 C. over 1 hour and then quenched with 1N HCl. The resulting mixture was stirred vigorously for 1 hour. The resulting mixture was extracted with ethyl acetate (3×). The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the desired compound as a white solid.

Reference： [1]Patent: WO2012/168817,2012,A1 .Location in patent: Page/Page column 44-45
[2]Patent: US2009/62269,2009,A1 .Location in patent: Page/Page column 54

11
[ 76283-09-5 ]
[ 720702-41-0 ]
[ 1159186-87-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 50℃; for 2 - 20h;	i -methyl-I H-pyrazol-5-ylboronic acid (224 mg, 1.78 mmol, 1 eq.), 4-bromo-1 - (bromomethyl)-2-fluorobenzene (500 mg, 1.87 mmol, 1.05 eq.), Pd(PPh3)4 (0.05 eq.) and 2N aq. Sodium carbonate solution (2.4 eq) were taken up in toluene:ethanol (4:3) and purged with nitrogen. The reaction mixture was heated at 50 0C for 2-20 h. The reaction mixture was concentrated. The residue was extracted with ether, dried over sodium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography eluting with gradient of 0-100% dichloromethane in hexanes to obtain 0.60 g of the intermediate as a crude oil. APCI(+) = 269, 271

Reference： [1]Patent: WO2009/69044,2009,A1 .Location in patent: Page/Page column 120

12
[ 121554-10-7 ]
[ 720702-41-0 ]
[ 1159186-42-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 80℃; for 1h;	5-Bromo-2-iodobenzonitrile (0.30 g, 1.0 mmol), (1 -methyl -1 H-pyrazol -5- yl)boronic acid (188 mg, 1.5 mmol), dichloro[1 ,1 '- bis(diphenylphosphino)ferrocene] palladium(ll) dichoromethane adduct (26 mg, 0.05 mmol) and cesium carbonate (651 mg, 2.00 mmol) were stirred together at 80 degrees Celsius in a solvent mixture of 3:1 dioxane/water (5 ml_), respectively, for one hour. The reaction mixture was allowed to cool to room temperature and water (25 ml_) and 1 N HCI (5 ml_) were added. The product was extracted into methyene chloride. The organic mixture was concentrated by rotary evaporation to a small volume which was applied to a 40 g cartridge of silica gel. The cartridge was eluted with a 70:30 mixture of hexanes-acetone, respectively. The fractions containing the product were combined and concentrated to give a white solid as product. (210 mg, 80 %)

Reference： [1]Patent: WO2009/69044,2009,A1 .Location in patent: Page/Page column 71-72

13
[ 116632-39-4 ]
[ 720702-41-0 ]
[ 1159186-49-8 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 20 - 70℃; for 4.5h;	0.1 g of 1 -bromo-4-iodo-5-methylbenzene, 0.043 g of 1 -methyl-1 H-pyrazol -5- ylboronic acid, and 0.045 g of 1 ,1 '-Bis(diphenylphosphino)ferrocene]- dichloropalladium(ll) were placed in a septum-sealed vial and evacuated/nitrogen filled three times. 3 ml_ of 1 ,4-dioxane was then added, followed by the addition of 0.5 ml_ of 1 M cesium carbonate. The mixture was stirred at room temperature for 30 minutes and heated at 7O C for 4 hours. The reaction mixture was cooled, diluted with water, and extracted with ethyl acetate. The ethyl acetate was dried with sodium sulfate, filtered, concentrated, and the residue was purified by reverse phase HPLC to give 0.05 g of product. LCMS (M+H): 252

Reference： [1]Patent: WO2009/69044,2009,A1 .Location in patent: Page/Page column 82

14
[ 1159186-43-2 ]
[ 720702-41-0 ]
[ 1159186-44-3 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 80℃; for 0.583333h;	102.7 mg of 5-bromo-2,3-dichloropyridine, 52.8 mg of 1 -methylpyrazole-5- boronic acid, and 24.9 mg of 1 ,1 '-bis(diphenylphosphino)ferrocene palladium dichlohde dichloromethane add uct were placed in a septum sealed vial and evacuated/nitrogen filled three times. 2.00 ml_ of anhydrous dioxane and 0.630 of nitrogen saturated aqueous 2M cesium carbonate were added , and the mixture was heated at 800C for 20 minutes. The reaction was cooled, and 43.2 mg more of 1 -methylpyrazole-5-boronic acid was added before heating another 15 minutes. The reaction was cooled, diluted into ethyl acetate, extracted with water, dried with magnesium sulfate, filtered, and flash chromatographed to give 50.2 mg of product. LCMS (M+H) 27; 1H NMR (400 MHz, DMSO-c/e) delta ppm 3.79 - 3.88 (m, 3 H) 6.68 (d, J=1.88 Hz, 1 H) 7.54 (d, J=1.88 Hz, 1 H) 8.53 (d, J=1.88 Hz, 1 H) 8.83 (d, J=2.15 Hz, 1 H).

Reference： [1]Patent: WO2009/69044,2009,A1 .Location in patent: Page/Page column 78

15
[ 1159186-47-6 ]
[ 720702-41-0 ]
[ 1159185-54-2 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 70℃; for 0.5h;	117.5 mg of 4-{3-[(4-bromo-2-chlorophenyl)thio]phenyl}tetrahydro-2H-pyran-4- carboxamide, 130.1 g of (1 -methyl -1 H-pyrazol-5-yl)boronic acid, and 38.1 mg of 1 ,1 '-bis(diphenylphosphino)ferrocene palladium dichlohde dichloromethane adduct were placed in a vial and evacuated/nitrogen filled three times. 2 ml_ of anhydrous dioxane and 0.55 ml_ of 2 M aqueous cesium carbonate were added, and the mixture was heated at 700C for 30 minutes, cooled, diluted the dioxane phase into ethyl acetate, dried with magnesium sulfate, filtered, concentrated, and purified by reverse phase chromatography to give 71.9 mg of product. HRMS (M+H) calc. 428.1199, found 428.1133; 1 H NMR (400 MHz, DMSO-c/e) delta ppm 1.82 (ddd, J=13.70, 10.47, 3.76 Hz, 2 H) 2.43 (d, J=13.96 Hz, 2 H) 3.47 (t, J=10.20 Hz, 2 H) 3.73 (dt, J=11.75, 3.52 Hz, 2 H) 3.85 (s, 3 H) 6.46 (d, J=1.88 Hz, 1 H) 6.92 (d, J=8.32 Hz, 1 H) 7.09 (br. s., 1 H) 7.30 (br. s., 1 H) 7.37 - 7.48 (m, 3 H) 7.50 (d, J=5.10 Hz, 2 H) 7.55 (s, 1 H) 7.72 (d, J=1.88 Hz, 1 H).

Reference： [1]Patent: WO2009/69044,2009,A1 .Location in patent: Page/Page column 81

16
[ 1285513-32-7 ]
[ 720702-41-0 ]
[ 1285515-05-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 120℃; for 0.416667h;microwave irradiation; Sealed vial;	To a microwave vial was added 5-bromo-2-[(pheny[methyl)oxy]-N-3-pyridinylbenzamide (may be prepared as described in example 2; 100 mg, 0.26 mmol), 1-methyl-5-(4,4,5,5- tetramethyi-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (59.7 mg, 0.29 mmol), 1 ,2- dimethoxyethane (2 ml), 1 sodium carbonate (0.52 ml, 0.52 mmol) andtetrakis(triphenylphosphine)palladium(0)(18.09 mg, 0.02 mmol). The vial was sealed and heated to 120C for 25 min under microwave conditions. The mixture was evaporated and water (5 ml) was added to the residue, the mixture was extracted with ethyl acetate (3 x 10 ml). The organics were combined and evaporated in vacuo and the residue was purified using the MDAP to yield the title compound. 22 mg.MS (electrospray): m/z [M+H]+ = 3851H NMR (400 MHz, CHLOROFORM-d) 3.93 (3 H, s), 5.30 (2 H, s), 6.35 (1 H, d, J=1.75 Hz), 7.15 - 7.34 (2 H, m), 7.45 - 7.68 (7 H, m), 7.97 (1 H, br. s.), 8.14 (1 H, d, J=8.33 Hz), 8.24 - 8.34 (1 H, m), 8.42 (1 H, d, J=2.41 Hz), 10.03 (1 H, s)

Reference： [1]Patent: WO2011/38572,2011,A1 .Location in patent: Page/Page column 152; 153

17
[ 1285514-37-5 ]
[ 720702-41-0 ]
[ 1285515-03-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 120℃; for 1h;	(1- ethyl-1 H-pyrazol-5-yl)boronic acid (30.1 mg, 0.24 mmol), sodium carbonate (0.40 ml, 0.40 mmol) andtetrakis(triphenylphosphine)palladium(0)(13.82 mg, 0.01 mmol) were added to a solution of 5-bromo-2-[(4- fluorophenyi)methyl]oxy}-N-3-pyridinylbenzamide (may be prepared as described in Example 59; 80 mg, 0.20 mmol) in 1 ,2-dimethoxyethane (3 ml). The mixture was heated at 120C for 1 hour. The solvent was removed in vacuo and purified by MDAP to yield the title compound as a brown gum. 13 mg.MS (electrospray): m/z [ +H]+ = 4031H NMR (DMSO-cfe): 3.86 (3 H, s), 5.29 (2 H, s), 6.42 (1 H, d, J=1.75 Hz), 7.14 - 7.28 (2 H, m), 7.33 - 7.43 (2 H, m), 7.46 (1 H, d, J=1.75 Hz), 7.60 (2 H, dd, .7=8.55, 5.70 Hz), 7.69 (1 H, dd, J=8.55, 2.41 Hz), 7.75 (1 H, d, J=2.41 Hz), 8.04 - 8.18 (1 H, m), 8.29 (1 H, dd, J=4.60, 1.32 Hz), 8.73 (1 H, d, J=2.41 Hz), 10.42 (1 H, s)

Reference： [1]Patent: WO2011/38572,2011,A1 .Location in patent: Page/Page column 151; 152

18
C₉H₇BrFN₃ [ No CAS ]
[ 720702-41-0 ]
C₁₃H₁₂FN₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 2732 - 2735

19
[ 114250-18-9 ]
[ 720702-41-0 ]
[ 1354786-74-5 ]

Yield	Reaction Conditions	Operation in experiment
67%	With dipotassium hydrogenphosphate;tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; at 100℃; for 18h;Inert atmosphere;Product distribution / selectivity;	Solution A: A stirred mixture of 4-(benzyloxy)-3-bromobiphenyl (7.5 g, 22.1 mmol, J. Med. Chem. 1988, 31, 1437-1445) and <strong>[720702-41-0](1-methyl-1H-pyrazol-5-yl)boronic acid</strong> (2.8 g, 22.1 mmol) in 1,4-dioxane (59 mL) was purged with argon for 20 minutes. Tris(dibenzylideneacetone)dipalladium (0) (810 mg, 0.88 mmol) and tricyclohexyl phosphine (495 mg, 1.8 mmol) were added.Solution B: In a separate flask dipotassium phosphate (9.4 g, 44.2 mmol) was dissolved in water (29 mL) and was also purged with argon for 20 minutes.Solution B was added to solution A and the resulting mixture was heated at 100 C. for 18 hours. After cooling to room temperature, the mixture was filtered through a pad of silica gel, and washed with ethyl acetate. The filtrate was concentrated in vacuo, diluted with ethyl acetate, washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel column chromatography (20% Et2O in hexane) to afford the title compound (5.0 g, 67%).1HNMR (d6-DMSO): delta 3.67 (s, 3H), 5.21 (s, 2H), 6.35 (s, 1H), 7.31-7.46 (m, 10H), 7.55 (s, 1H), 7.67 (d, 2H), 7.73-7.76 (m, 1H)

Reference： [1]Patent: US2012/10182,2012,A1 .Location in patent: Page/Page column 37-38

20
[ 1365238-05-6 ]
[ 720702-41-0 ]
[ 1365239-05-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 120℃; for 2h;Inert atmosphere; microwave irradiation;	Example 202; N-cyclopropyl-2-methyl-4-{8-[(2-methylpropyl)amino]-6-(1 -methyl- 1 H- razol-5-yl)imidazo[ 1 ,2-b]pyridazin-3-yl}benzamide; To a mixture of 100 mg (251 muetaiotaomicron)4-[6-chloro-8-(isobutylamino)imidazo[1 ,2-b]pyridazin-3-yl]-N-cyclopropyl-2-methylb enzamide, which was prepared according to example 194a, 95 mg (750 mu?iotaomicron) 1 -methyl-1 H-pyrazol-5-yl) boronic acid, 35 mgTetrakis(triphenylphosphin)palladium in 2 mL of ethanol and 2 mL of toluene was added 0.5 mL of an aqueous 10% sodiumbicarbonate solution and the mixture was stirred at 120 C for 2 hours under microwave irradiation. Then water and was added and the organic layer was washed with water and brine, concentrated and purified by chromatography to give 99 mg of the title compound.1 H-NMR (DMSO-d6): delta= 0.49-0.67 (4H), 0.93 (6H), 2.00 (1 H), 2.36 (3H), 2.80 (1 H), 3.21 (3H), 4.13 (3H), 6.46 (1 H), 6.90 (1 H), 7.37 (1 H), 7.50 (1 H), 7.65 (1 H), 7.92 - 7.97 (3H), 8.29 (1 H) ppm.

Reference： [1]Patent: WO2012/32031,2012,A1 .Location in patent: Page/Page column 268

21
[ 1365243-75-9 ]
[ 720702-41-0 ]
[ 1365238-95-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 120℃; for 2h;Inert atmosphere; microwave irradiation;	Example 192; N-cyclopropyl-4-[8-({(2S)-2-[(4R)-2,2-dimethyl-1 ,3-dioxolan-4-yl]-2- hydroxyethyl}amino)-6-( 1 -methyl-1 H-pyrazol-5-yl)imidazo[ 1 ,2-b]pyridazin-3-yl] benzamide; To a mixture of 52 mg (94 pmol)4-[6-chloro-8-({(2S)-2-[(4R)-2,2-dimethyl-1 ,3-dioxolan-4-yl]-2-hydroxyethyl}amino)i midazo[1 ,2-b]pyridazin-3-yl]-N-cyclopropylbenzamide which was prepared according to intermediate example 192a, 33 mg 1 -methyl-1 H-pyrazol-5-yl) boronic acid, 6.5 mg tetrakis(triphenylphosphin)palladium in 1 mL of ethanol and 1 mL of toluene was added 0.26 mL of an aqueous 10% sodiumbicarbonate solution and the mixture was stirred at 120C for 2 hours under microwave irradiation. Then the mixture was filtered, the solvent was removed and the residue was purified by chromatography to give 36 mg of the title compounds. 1 H-NMR (DMS0-d6): delta= 0.49-0.68 (4H), 1.24 (3H), 1.32 (3H), 2.62 (1 H), 3.31 - 3.95 (3H), 3.60 - 4.05 (3H), 4.12 (3H), 6.54 (1 H), 6.85 (1 H), 7.31 (1 H) 7.90 (2H), 8.07 (1 H), 8.18 (2H), 8.45 (1 H), ppm.

Reference： [1]Patent: WO2012/32031,2012,A1 .Location in patent: Page/Page column 260-261

22
[ 1380106-79-5 ]
[ 720702-41-0 ]
C₁₈H₂₀ClN₃O₃ [ No CAS ]

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

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

23
[ 106-38-7 ]
[ 720702-41-0 ]
[ 73387-56-1 ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; for 3h;Inert atmosphere; Reflux;	Step 2: Synthesis of 5-(4-methylphenyl)-1-methyl-1H-pyrazole (C2) A mixture of (1-methyl-1 /- -pyrazol-5-yl)boronic acid (C1 ) (60.0 g, 0.476 mol) and 1- bromo-4-methylbenzene (75.0 g, 0.438 mol) in a mixture of 1 ,2-dimethoxyethane (1 .2 L) and 2 M aqueous sodium carbonate solution (550 mL) was degassed and purged with N2; this procedure was then repeated twice. Dichlorobis(triphenylphosphine)palladium(ll) (3.1 g, 4.4 mmol) was added and the mixture was purged twice with N2. The reaction mixture was heated to reflux and stirred under N2 for 3 hours. The mixture was cooled and 1 ,2-dimethoxyethane was removed under reduced pressure; water (500 mL) was added to the residue, and the resulting mixture was extracted with dichloromethane (3 x 500 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Eluent: 100:1 petroleum ether/ethyl acetate) provided the product as a yellow liquid. Yield: 55.0 g, 319 mmol, 73%. H NMR (400 MHz, CDCI3) delta 2.42 (s, 3H), 3.89 (s, 3H), 6.29 (d, J=1.8 Hz, 1 H), 7.29 (br AB quartet, JAB=8 HZ, DeltanuAlphaBeta=18 Hz, 4H), 7.52 (d, J=2.0 Hz, 1 H).
42%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 80℃; for 18h;	Example 1 4-(Azetidin-1-yl)-7-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]imidazo[5,1-f][1,2,4]triazineStep 1. Synthesis of 2-bromo-1-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]ethanoneA. Preparation of 1-methyl-5-(4-methylphenyl)-1H-pyrazole(1-Methyl-1H-pyrazol-5-yl)boronic acid (2.0 g, 16 mmol), 1-bromo-4-methylbenzene (1.96 mL, 15.9 mmol), sodium carbonate (5.05 g, 47.6 mmol) and dichlorobis(triphenylphosphine)palladium(II) (557 mg, 0.794 mmol) were combined in a mixture of water (20 mL) and 1,2-dimethoxyethane (100 mL), and heated at 80 C. for 18 hours. After the reaction mixture had cooled, it was filtered through Celite, and concentrated in vacuo. The residue was partitioned between water and ethyl acetate, and the aqueous layer was extracted with additional ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Chromatography on silica gel (Gradient: 0% to 50% ethyl acetate in heptane) provided the product as a yellow oil. Yield: 1.15 g, 6.68 mmol, 42%. LCMS m/z 173.1 (M+1). 1H NMR (400 MHz, CDCl3) delta 2.42 (s, 3H), 3.89 (s, 3H), 6.29 (d, J=2.0 Hz, 1H), 7.30 (br AB quartet, JAB=8 Hz, DeltavAB=18 Hz, 4H), 7.51 (d, J=1.9 Hz, 1H).

Reference： [1]Patent: WO2012/168817,2012,A1 .Location in patent: Page/Page column 45
[2]Patent: US2012/214791,2012,A1 .Location in patent: Page/Page column 19

24
[ 149108-74-7 ]
[ 720702-41-0 ]
[ 1401304-39-9 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 80℃; for 18h;	To a solution of tert-butyl 5-(trifluoromethylsulfonyloxy)-3,4-dihydropyridine-1(2H)-carboxylate (2.0 g, 6.0 mmol) in dioxane (40 mL) was added <strong>[720702-41-0]1-methyl-1H-pyrazol-5-ylboronic acid</strong> (0.83 g, 6.60 mmol), Na2CO3 (1.90 g, 18.1 mmol), and Pd(dppf)Cl2 (370 mg, 0.600 mmol). The resulting mixture was stirred at 80 C. for 18 h. After concentration, the residue was purified by silica gel chromatography eluting with a 0-25% gradient of EtOAc in petroleum ether to give tert-butyl 5-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydropyridine-1(2H)-carboxylate (0.80 g, 58% yield) as pale yellow oil. LCMS (ESI) m/z: 263.2 [M+H+].

Reference： [1]Patent: US2012/245144,2012,A1 .Location in patent: Page/Page column 164

25
[ 930-36-9 ]
[ 121-43-7 ]
[ 720702-41-0 ]

Yield	Reaction Conditions	Operation in experiment
93%		A solution of <strong>[930-36-9]1-methylpyrazole</strong> (25.0 g, 305 mmol) in tetrahydrofuran (THF) (600 mL) was cooled to 0 C. n-Butyl lithium (1.6 M in hexanes, 209 mL, 335 mmol) was added drop-wise over 1 h, keeping the temperature below 7 C. The solution was stirred at room temperature (rt) for 3 h before cooling to -70 C. B(OMe)3 (44.4 mL, 0.40 mol) was slowly added, keeping the reaction temperature below -65 C. The resulting mixture was allowed to warm to rt, before it was quenched with 15% aqueous (aq) NH4Cl (450 mL). The mixture was extracted with THF (3 × 500 mL), and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give a yellowish solid (15.6 g, 41%). The aq layer was concentrated in vacuo, and the resulting solid was repeatedly extracted with THF (5 × 250 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo, yielding a yellow solid (20.3 g, 52%). The combined yield of (1-methyl-1H-pyrazol-5-yl)boronic acid was 35.9 g (93%), and 20.3 g (161 mmol) of this material was esterified with pinacole (28.4 g, 240 mmol) in THF (200 mL). 4 A molecular sieves (6.0 g dried in vacuo at 50 C) were added, and the resulting mixture was stirred at rt for 2 days. The sieves were filtered off, and the filtrate was concentrated in vacuo. The resulting crude product was dissolved in heptane (500 mL) and washed with water (2 × 250 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to afford a white solid. This material was recrystallized from acetonitrile yielding white crystals (22.5 g, 67%). Mp 71.0-71.6 C (Ivachtchenko et al.,21 74-76 C). 1H NMR (500 MHz, DMSO-d6): delta, 7.46 (d, J = 1.9 Hz, pyrazole H-3), 6.62 (d, J = 1.9 Hz, pyrazole H-4), 3.98 (s, N-methyl), 1.30 (s, pinacol methyl groups, 12H). 13C NMR (126 MHz, DMSO-d6): delta, 138.3, 115.9, 84.4 (2C), 41.9, 24.9 (4C). Anal. calcd for C10H17BN2O2: C, 57.73; H, 8.24; N, 13.46. Found: C, 57.72; H, 8.08; N, 13.40.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 196 - 204

26
[ 50488-42-1 ]
[ 720702-41-0 ]
[ 1356997-31-3 ]

Yield	Reaction Conditions	Operation in experiment
35%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; for 18h;Reflux;	Step 2: Synthesis of 2-(1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)pyridine (C13)(1 -Methyl-1 /- -pyrazol-5-yl)boronic acid (C1 ) (1.00 g, 7.94 mmol), 2-bromo-5-(trifluoromethyl)pyridine (1 .79 g, 7.92 mmol), dichlorobis(triphenylphosphine)palladium(ll) (279 mg, 0.397 mmol), and sodium carbonate (3.37 g, 31.8 mmol) were combined in 1 ,2- dimethoxyethane (30 mL) and water (3 mL), and the reaction mixture was heated at reflux for 18 hours. After the reaction had cooled to room temperature, it was concentrated in vacuo, diluted with additional water, and extracted with ethyl acetate (2 x 300 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) provided the product. Yield: 630 mg, 2.77 mmol, 35%. H NMR (400 MHz, CD3OD) delta 3.95 (s, 3H), 6.60 (d, J=2.2 Hz, 1 H), 7.58 (d, J=2.0 Hz, 1 H), 7.94 (br d, J=8.2 Hz, 1 H), 8.19-8.23 (m, 1 H), 8.89 (br d, J=2 Hz, 1 H).

Reference： [1]Patent: WO2012/168817,2012,A1 .Location in patent: Page/Page column 52
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 5673 - 5698

27
[ 1346245-20-2 ]
[ 720702-41-0 ]
[ 1431700-82-1 ]

Yield	Reaction Conditions	Operation in experiment
67%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 6h;	A mixture of intermediate 21 (238 mg; 0.64mmol), 2-Methyl-2H-pyrazole-3-boronic acid (161 mg; 0.77 mmol), Pd(PPh3)4 (74 mg; 0.064 mmol) and a 2M aq. solution of Na2C03 (0.64 mL; 1.28 mmol) in DME (3.5 mL) were heated for 6 h at 100C. The r.m. was cooled down to r.t., poured onto aq. K2C03 and extracted with EtOAc. The organic layer was dried over MgS04, filtered and concentrated. The residue was purified by chromatography over silica gel (Irregular SiOH 15-40pm 30g; mobile phase: gradient 100% DCM, 0% MeOH to 98% DCM, 2% MeOH). The fractions containing the product were mixed and concentrated to give 300 mg of fraction A (impure).Fraction A was purified by column chromatography over silica gel (Irregular SiOH 15- 40pm 30g; mobile phase: gradient 100% DCM, 0% MeOH to 98% DCM, 2% MeOH). The pure fractions were mixed and concentrated to give 225 mg (84%) of anintermediate fraction which was crystallized from a mixture of DIPE/Et20. The precipitate was filtered to afford 179 mg (67%) of compound 18 (MP: 132C DSC).

Reference： [1]Patent: WO2013/61081,2013,A1 .Location in patent: Page/Page column 199; 200

28
[ 313405-50-4 ]
[ 720702-41-0 ]
[ 1448015-81-3 ]

Reference： [1]ChemMedChem,2013,vol. 8,p. 847 - 857

29
[ 1310049-89-8 ]
[ 720702-41-0 ]
[ 1426259-45-1 ]

Reference： [1]ChemMedChem,2013,vol. 8,p. 847 - 857

30
20-acetyl-7-chlorocamptothecin [ No CAS ]
[ 720702-41-0 ]
[ 1579279-85-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In 1,4-dioxane; at 120℃; for 0.5h;Inert atmosphere; Microwave irradiation;	General procedure: Compound 7(1eq), 8c (1.5eq), Pd(PPh3)4 (0.1eq) and CsF (2eq) were dissolvedin dioxane (5 mL) in a microwave vial under nitrogen atmosphere and thereaction mixture was irradiated in a microwave apparatus at 120 C for 30 min.After the reaction mixture was cooled to ambient temperature, the crude mixturewas purified by silica gel column chromatography (chloroform: acetone = 30: 1) to afford 9a-g.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 1597 - 1599

31
[ 1609581-10-3 ]
[ 76-05-1 ]
[ 720702-41-0 ]
[ 1609577-18-5 ]

Yield	Reaction Conditions	Operation in experiment
9%		4-[(4-Bromophenyl)sulfanyl]furo[3,2-c]pyridine (Cl 3) (210 mg from the previous step), (1-methyl-i H-pyrazol-5-yl)boronic acid (104 mg, 0.826 mmol), triphenylphosphine (21.5 mg, 0.0819 mmol) and potassium carbonate (190 mg, 1.37 mmol) were combined in N,Ndimethylformamide (6 mL) and water (2 mL), and the mixture was degassed with nitrogen for 20minutes. Palladium(ll) acetate (98%, 4.8 mg, 0.021 mmol) was added, and the reaction mixturewas heated at 80 00 for 18 hours. After cooling to room temperature, the reaction mixture was diluted with water (15 mL) and extracted with 1:1 ethyl acetate hexanes (3 x 15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification was effected first via silica gel chromatography (Eluent: 80% ethyl acetate inheptane), followed by HPLC (Column: Waters XBridge 018, 5 pm; Mobile phase A: water with trifluoroacetic acid modifier; Mobile phase B: acetonitrile with trifluoroacetic acid modifier; Gradient: 40% to 100% B), to afford the product as a white solid. Yield: 30 mg, 0.071 mmol, 9% over two steps. LCMS m/z 308.0 (M+H). 1H NMR (400 MHz, CD3OD) oe 8.29 (d, J=5.8 Hz, 1 H), 7.87 (d, J=2.2 Hz, 1H), 7.61 (brd, J=8.6 Hz, 2H), 7.53 (brd, J=8.7 Hz, 2H), 7.51 (d, J=2.1 Hz,1H), 7.49 (dd, J=5.8, 1.0 Hz, 1H), 6.66 (dd, J=2.3, 1.1 Hz, 1H), 6.42 (d, J=2.0 Hz, 1H), 3.90 (s,3H).

Reference： [1]Patent: WO2014/72881,2014,A1 .Location in patent: Page/Page column 82; 83

32
[ 1609581-47-6 ]
[ 720702-41-0 ]
[ 1609580-80-4 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In methanol; water; at 120℃; for 0.833333h;Inert atmosphere; Microwave irradiation;	General procedure: To a solution of 5-(furo[3,2-c]pyrid in-4-yloxy)-2-(4,4,5,5-tetramethyl-1 ,3,2-d ioxaborolan2-yl)benzyl acetate (C34)(82 mg, 0.20 mmol) in 1,4-dioxane (10 mL)were added 5-bromo-4,6- dimethylpyrimidine (41 mg, 0.22 mmol), potassium carbonate (83 mg, 0.6 mmol), [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(ll) (44 mg, 0.060 mmcl) and water (5 drops) at room temperature. The reaction mixture was degassed with nitrogen for 5 minutes, thensubjected to microwave irradiation at 12000 for 50 minutes. After filtration of the reactionmixture, the filtrate was concentrated in vacuo; purification was carried out by preparative thinlayer chromatography to give the product. Yield: 28 mg, 0.072 mmol, 36%. LCMS m/z 389.9(M+H).

Reference： [1]Patent: WO2014/72881,2014,A1 .Location in patent: Page/Page column 96; 97; 158

33
(S)-methyl 1-(3-fluoro-2-methylphenyl)-3-(((trifluoromethyl)sulfonyl)oxy)cyclopent-2-enecarboxylate [ No CAS ]
[ 720702-41-0 ]
(S)-methyl 1-(3-fluoro-2-methylphenyl)-3-(1-methyl-1H-pyrazol-5-yl)cyclopent-2-enecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
221 mg	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; 1,2-dimethoxyethane; at 120℃; for 2h;Inert atmosphere;	General procedure: Method B (Suzuki coupling) [00174] To a solution of methyl 1 -(3-fluoro-2-methylphenyl)-3- (((trifluoromethyl)sulfonyl) oxy)cyclopent-2-enecarboxylate (0.5 g, 1 .31 mmol) in 1 ,2 dimethoxyethane (8 ml_) was added boronic acid (1 .31 mmol), potassium carbonate (0.362 g, 2.62 mmol) and water (4 ml_). The reaction mixture was heated to 60 C at which time a colorless solution formed. [1 ,1 '- Bis(diphenylphosphino)ferrocene] dichloropalladium(ll), complex with dichloromethane (0.06 g, 0.07 mmol) was added and the reaction mixture was heated to 80 C under N2 for 2 h. After this time the reaction mixture was cooled to r.t. and filtered through Celite, washing with EtOAc (3 x 10 ml_). Combined organics were extracted with water (1 5 ml_) then brine (20 ml_). EtOAc layers were then dried, filtered (phase separation cartridge) and concentrated to give a brown residue.

Reference： [1]Patent: WO2014/159224,2014,A1 .Location in patent: Paragraph 00174; 00272

34
2-bromo-6-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-ethyl-5,6-dihydropyrrolo[3,4-d]imidazol-4(3H)-one [ No CAS ]
[ 720702-41-0 ]
6-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-ethyl-2-(1-methyl-1H-pyrazol-5-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere;	To a stirred mixture of 1 -allyl-2-bromo-6-(4-chlorophenyl)-5-(3, 7-dimethyl-3H-benzo[d][1 ,2,3]triazol-5-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1 H)-one (Step 1.11) (80 mg, 0.161 mmol) in Dioxane (1.1 mL) and water (400 iL) under Ar were added K3P04 (136 mg,0.643 mmol), PdCI2(dppf).CH2CI2 adduct (20 mg, 0.0.24 mmol) and trimethylboroxine (45 iL,0.32 mmol). The resulting mixture was heated up and stirred at 100 00 overnight. PdCI2(dppf).CH2CI2 adduct (20 mg, 0.0.24 mmol) and trimethylboroxine (45 iL, 0.32 mmol) were added and the reaction was stirred 1.5 hr at 100 00 PdCI2(dppf).CH2CI2 (20 mg, 0.0.24 mmol) adduct and trimethylboroxine trimethylboroxine (45 iL, 0.32 mmol) were added and the reaction was stirred 5.5 hr at 100 00 The reaction was cooled down to RT, diluted with water and the aq. layer was extracted twice with EtOAc. Combined extracts were dried over Na2504, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (gradient 35-55 % CH3CN in 16 mm) followed by basic workup to afford the title product (5 mg, 0.012 mmol, 7.52 % yield). tR: 0.80 mm (LC-MS 2); ESl-MS: 393 [M+H] ESl-MS: 391 [M-H] (LC-MS 2).The title compound was prepared in analogy to the procedure described for Example 1 using 2- bromo-6-(4-chlorophenyl)-5-(1 ,5-dimethyl-6-oxo-1 ,6-dihydropyridin-3-yl)-3-ethyl-5,6-dihydro- pyrrolo[3,4-d]imidazol-4(3H)-one (Step 38.9) and <strong>[720702-41-0](1-methyl-1H-pyrazol-5-yl)boronic acid</strong> at 100 00 for 2 hr. The crude product was first purified by silica gel column chromatography (hexane/(CH2CI2/MeOH 19:1) 50-100 % (CH2CI2/MeOH 19:1)) followed by preparative achiralSF0 (column Silica, gradient 20-25 % over 6 mm_total ii mm) to afford a yellow foam. tR: 0.85mm (LC-MS 2); ESl-MS: 463/465 [M+H] (LC-MS 2);; TLC (CH2CI2/MeOH 19:1) Rf = 0.33; 1HNMR (400 MHz, DMSO-d6) O ppm 1.49 (t, J=7.2 Hz, 3 H) 1.96 (s, 3 H) 3.39 (s, 3 H) 3.90 (s, 3 H)4.16- 4.26 (m, 2 H) 6.20 (s, 1 H) 6.73 (d, J=2.1 Hz, 1H) 7.30 (d, J=8.4 Hz, 2 H) 7.41 (d, J=8.4Hz, 2 H) 7.44 (m, 1 H) 7.63 (d, J=2.0 Hz, 1 H) 7.75 (d, J=2.7 Hz, 1 H).

Reference： [1]Patent: WO2014/191894,2014,A1 .Location in patent: Page/Page column 60; 119; 120

35
[ 3764-01-0 ]
[ 720702-41-0 ]
2,4-dichloro-6-(1-methyl-1H-pyrazol-5-yl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With bis-triphenylphosphine-palladium(II) chloride; cesium fluoride; In ethanol; water; at 100℃; for 1h;	General procedure: Aryl halide, palladium(II) bis(triphenylphosphine) dichloride or (triphenylphosphine) palladium (0.05eq), boronic acid or pinacol ester (1.1 eq) and cesium fluoride (2 eq) were weighed out into a microwave vessel or sealed tube. Ethanol (3 mL/mmol) and water (0.6 mL/mmol) were added. The vessel was capped and heated thermally or in a microwave vessel at 70-100 C. for 1 hour. The reaction mixture wasconcentrated under vacuum and the residue was purified by silica gel columnchromatography to afford the Suzuki coupling product.
51%	With bis-triphenylphosphine-palladium(II) chloride; cesium fluoride; In ethanol; water; at 100℃;Microwave irradiation;	Similar to as described in General Procedure X, 2,4,6-trichloropyrimidine was reacted with <strong>[720702-41-0](1-methyl-1H-pyrazol-5-yl)boronic acid</strong> to give the title compound (256 mg, 51%) as an off-whitesolid. LC-MS (ES, mlz): 229 [M+H]. Aryl halide, palladium (II) bis(triphenylphosphine) dichloride or tetrakis (triphenylphosphine) palladium (0.OSeq), boronic acid or pinacol ester (1. leq) and cesium fluoride (2eq) were weighed out into a microwave vessel or sealed tube. Ethanol (3 mL/mmol) and water (0.6 mL/mmol) were added. The vessel was capped and heated thermally or in a microwave vessel at 70-400 C for 1 hour. The reaction mixture was concentrated under vacuum and the residue was purified by silicagel column chromatography to afford the Suzuki coupling product.

Reference： [1]Patent: US2015/57260,2015,A1 .Location in patent: Paragraph 0548; 0549; 0613; 0614
[2]Patent: WO2015/25026,2015,A1 .Location in patent: Page/Page column 137; 150

36
2-(7-bromo-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-2-methyl-1H-indol-1-yl)acetic acid [ No CAS ]
[ 720702-41-0 ]
2-(3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-2-methyl-7-(1-methyl-1H-pyrazol-5-yl)-1H-indol-1-yl)acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In methanol; N,N-dimethyl-formamide; at 120℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	Example 64 Preparation of 2-(3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-2-methyl-7-(l-methyl-lH- pyrazol-5-yl)-lH-indol-l-yl)acetic acid To a solution of 2-(7-bromo-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-2-methyl-lH- indol-l-yl)acetic acid (50 mg, 0.108 mmol) in MeOH/DME (1/2 mL) was added cesium fluoride (49 mg, 0.324 mmol), Pd(PPh3)4 (7 mg, cat.), and (1 -methyl- lH-pyrazol-5-yl)boronic acid (15 mg, 0.118 mmol) under Ar at room temperature. The reaction mixture was heated at 120C for 20 min under microwave condition and solvent was concentrated in vacuo. The residue was purified by column chromatography using dichloromethane/MeOH (Combi-flash Rf, 0 to 30% MeOH gradient) to afford the title compound. 1H NMR (MeOD, 400 MHz) delta (ppm) 7.61 (d, J = 7.2 Hz, 1H), 7.58 (d, J = 2.0 Hz, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.90 (d, J = 6.8 Hz, 1H), 6.69 (s, 2H), 6.36 (d, J = 2.0 Hz, 1H), 4.47 (d, J = 18.8 Hz, 1H), 4.17 (d, J = 18.8 Hz, 1H), 3.91 (t, J = 6.0 Hz, 2H), 3.58 (s, 3H), 2.98 (t, J= 6.8 Hz, 2H), 2.32 (s, 6H), 2.23 (s, 3H), 2.08 (qt, J= 6.4 Hz, 2H); LCMS (ESI) tR: 1.324 min (>99%, ELSD), m/z: 466.1 (M+H).

Reference： [1]Patent: WO2015/31608,2015,A1 .Location in patent: Paragraph 00428

37
methyl 3-(7-bromo-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-2-methyl-1H-indol-1-yl)propanoate [ No CAS ]
[ 720702-41-0 ]
3-(3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-2-methyl-7-(1-methyl-1H-pyrazol-5-yl)-1H-indol-1-yl)propanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; water; sodium carbonate; In 1,2-dimethoxyethane; ethanol; at 150℃; for 0.5h;Microwave irradiation;	Step B. To a solution of methyl 3-(7-bromo-3-(3-(4-chloro-3,5- dimethylphenoxy)propyl)-2-methyl-lH-indol-l-yl) propanoate (50 mg, 0.10 mmol) in 2.4 mL of DME/EtOH/H20 (7:2:3) was added sodium carbonate (0.6 mL, 1M solution), Pd(PPh3)2Cl2 (7 mg, cat.), and (1 -methyl- lH-pyrazol-5-yl)boronic acid (38 mg, 0.30 mmol) at room temperature. The reaction mixture was heated at 150C for 30 min under microwave condition and solvent was concentrated in vacuo. The residue was purified by column chromatography using dichloromethane/MeOH (Combi-flash Rf, 0 to 30% MeOH gradient) to afford the title compound. LCMS (ESI) tR: 1.348 min (>99%, ELSD), m/z: 480.1 (M+H).

Reference： [1]Patent: WO2015/31608,2015,A1 .Location in patent: Paragraph 00435

38
6-bromo-4-(2-fluoro-4-nitro-phenoxy)-pyrazolo[1,5-a]pyridine [ No CAS ]
[ 720702-41-0 ]
4-(2-fluoro-4-nitro-phenoxy)-6-(2-methyl-2H-pyrazol-3-yl)-pyrazolo[1,5-a]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With palladium diacetate; sodium carbonate; triphenylphosphine; In 1,4-dioxane; N,N-dimethyl-formamide; at 80℃;Schlenk technique; Inert atmosphere;	Step 2. 4-(2-Fluoro-4-nitro-phenoxy)-6-(2-methyl-2H-pyrazol-3-yl)-pyrazolo[1,5-a]pyridine. A Schlenk flask was charged with palladium acetate (0.03 g, 0.11 mmol), triphenylphosphine (0.12 g, 0.45 mmol), and 1,4-dioxane (2 mL) and stirred for 5 min until it turned bright yellow. 6-bromo-4-(2-fluoro-4-nitro-phenoxy)-pyrazolo[1,5- a]pyridine (0.2 g, 0.57 mmol), 5-(1-methyl-1H-pyrazole) boronic acid (0.09 g, 0.68 mmol), N,N-dimethylformamide (5 mL), and 1 M sodium carbonate solution (1.1 mL, 20 1.14 mmol) were added successively and the reaction was heated at 80 C overnight under an atmosphere of nitrogen. After cooling to rt, the mixture was diluted with dichloromethane, filtered through celite, and concentrated. The product was chromatographed on silica gel using a single step column (10-50% ethyl acetate/hexanes) and concentrated to give 0.08 g, 41%. LCMS m/z = 354 (M + 1).

Reference： [1]Patent: WO2015/100117,2015,A1 .Location in patent: Paragraph 0202

39
[ 59557-91-4 ]
[ 720702-41-0 ]
2-methoxy-4-(1-methyl-1H-pyrazol-5-yl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In tetrahydrofuran; water; at 70℃; for 18h;	General procedure: Preparation 45 (1126) -methoxy-4-(1 -methyl-1 -/-pyrazol-3-yl)aniline (1127) (1128) To a solution of 2-methoxy-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)aniline (310 mg, 1 .244 mmol) and 3-bromo-1 -methyl-1 -/-pyrazole (154 mg, 0.957 mmol) in THF (3 ml_) was added Pd(dppf)Cl2-DCM (40 mg, 0.049 mmol) and 2M aqueous Na2CC>3 (1 ml_) and the reaction was heated to 65 C for 18 hours. The reaction was diluted with EtOAc and water. The aqueous layer was extracted with EtOAc, the combined organic layers were washed with water and brine, dried (MgS04) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 0-60% EtOAc in cyclohexane to afford the title compound (34 mg, 18%). (1129) 1 H NMR (500 MHz, CDCI3): delta ppm 7.33 (d, J = 18.8 Hz, 2H), 7.28 (d, J = 1 .2 Hz, 2H), 7.20 (d, J = 7.9 Hz, 1 H), 6.74 (dd, J = 7.9, 1 .2 Hz, 1 H), 6.45 (dd, J = 2.2, 1 .2 Hz, 1 H), 3.95 (m, 6H), 3.85 (br s, 2H). (1130) HRMS (ESI) MS m/z calcd for C11 H14N3O [M+H]+ 204.1 131 , found 204.1 141 .

Reference： [1]Patent: WO2015/128676,2015,A1 .Location in patent: Page/Page column 123; 124

40
[ 15864-32-1 ]
[ 720702-41-0 ]
C₁₁H₁₀N₄S [ No CAS ]

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

41
[ 1258440-64-0 ]
[ 720702-41-0 ]
C₁₅H₁₅ClN₄OS [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1003 - 1020

42
(S)-6-chloro-3-(1-((4-chloropyrimidin-2-yl)amino)ethyl)quinolin-2(1H)-one [ No CAS ]
[ 720702-41-0 ]
6-chloro-3-[(1S)-1-[4-(1-methyl-1H-pyrazol-5-yl)pyrimidin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃;Inert atmosphere; Sealed tube;	A 2 mL reaction vial was charged with a 0.2M 1,4-dioxane solution containing (S)-3-(1-((4-bromopyrimidin-2-yl)amino)ethyl)-6-chloroquinolin-2(1H)-one IV-1 (100 muL, 20 mumol) and <strong>[720702-41-0](1-methyl-1H-pyrazol-5-yl)boronic acid</strong> (150 muL, 30 mumol, 1.5 equivalents). To the mixture was added 1M aqueous potassium phosphate tribasic solution (75 muL, 75 mumol, 3.75 equivalents). Nitrogen gas was then bubbled through the mixture for 3-5 seconds before a 0.01M solution of palladium tetrakis in 1,4-dioxane (50 muL, 0.5 mumol) was added. Nitrogen gas was passed through the mixture once more before the vial was sealed and heated to 100 C. overnight. LCMS analysis confirmed the presence of the cross-coupled product. The mixture was then diluted with brine (500 muL) and extracted with ethyl acetate (2*500 muL). The organic Layers were placed onto a 0.5 gram ion exchange column (benzenesulfonic acid on silica). The column was flushed with ethyl acetate (3 mL) and the title compound was eluted with 3 mL of a 10:1:1 solution of ethyl acetate/methanol/triethylamine. The eluent containing crude product was concentrated under a stream of nitrogen at 50 C. The resulting residue was dissolved in DMSO (500 muL), and purified by mass-triggered preparatory HPLC to afford the title compound (3.8 mg, 50% yield). LCMS (Method 4) Rt 1.18 min, m/z 381.04 [M+H]+.

Reference： [1]Patent: US2016/83365,2016,A1 .Location in patent: Page/Page column 91

43
tert-butyl 2-bromo-5-fluoro-1H-indole-1-carboxylate [ No CAS ]
[ 720702-41-0 ]
tert-butyl 5-fluoro-2-(1-methyl-1H-pyrazol-5-yl)-1H-indole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 70 - 80℃; for 3h;Inert atmosphere;	To a mixture of tert-butyl 2-bromo-5-fluoro-1H-indole-1-carboxylate (10.0 g, 0.032 mol) in dioxane (100 mL) and H2O (20 mL) was added (1-methyl-1H-pyrazol-5-yl) boronic acid (4.83 g, 0.038 mol) , Na2CO3(10.2 g, 0.096 mmol) and Pd (PPh3)4(1.0 g, 0.90 mmol) at 25 . The resulting mixture was divided into 10 portions then heated under N2at 70-80 for 3 h. All reaction portions were pooled and filtered. The filtrate was diluted with water (30 mL) and extracted with EtOAc (30 mL×3) . The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel (PE:EtOAc 5:1) to afford the title compound. MS: m/z 316.1 (M + 1) .1H NMR (400 MHz, CDCl3) delta 8.21-8.29 (m, 1H) , 7.49 -7.55 (m, 1H) , 7.26-7.27 (m, 1H) , 7.22-7.26 (m, 1H), 7.09-7.15 (m, 1H) , 6.61-6.64 (m, 1H) , 6.31-6.34 (m, 1H) , 3.73 (s, 3 H) , 1.59 (s, 3 H) , 1.37 (s, 9 H) .

Reference： [1]Patent: WO2016/54807,2016,A1 .Location in patent: Page/Page column 46; 47

44
[ 84249-14-9 ]
[ 720702-41-0 ]
4-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In water; toluene; for 2h;Inert atmosphere; Reflux;	Reference Example 19 4-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine (0407) 440 mg (3.49 mmol) of <strong>[720702-41-0](1-methyl-1H-pyrazol-5-yl)boronic acid</strong> and 1.70 g (16.1 mmol) of sodium carbonate were added at room temperature to a mixed solution of 400 mg (2.31 mmol) of 4-bromopyridin-2-amine, 90 mg (0.123 mmol) of [1,1?-bis(diphenylphosphino)ferrocene]palladium(2) dichloride, 20 ml toluene and 5 ml water. After completion of the addition, the air in the reaction vessel was replaced with nitrogen gas. After completion of the replacement, said reaction mixture liquid was stirred for 2 hours under a nitrogen gas atmosphere with heating under reflux. After completion of the stirring, the reaction was stopped by addition of 30 ml of water, and said reaction liquid was extracted with ethyl acetate (3×30 ml). The organic layer obtained was dried with anhydrous sodium sulfate, and the solvent distilled off under reduced pressure. The residue obtained was purified by silica gel chromatography (methanol:ethyl acetate=1:9), and 100 mg of the desired compound were obtained as a brown solid.

Reference： [1]Patent: US2016/221998,2016,A1 .Location in patent: Paragraph 0407

45
[ 4519-46-4 ]
[ 720702-41-0 ]
methyl 2-(1-methyl-1H-pyrazol-5-yl)acrylate [ No CAS ]

Reference： [1]MedChemComm,2016,vol. 7,p. 1340 - 1351

46
[ 3959-07-7 ]
[ 720702-41-0 ]
C₁₁H₁₃N₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With 1,1'-bis-(diphenylphosphino)ferrocene; potassium phosphate; bis(dibenzylideneacetone)-palladium(0); In 1,4-dioxane; water; at 100℃;Inert atmosphere;	p-bromobenzylamine (800mg, 4.30mmol) were dissolved in dioxane / water, was added A39-1 (1.52g, 12.1mmol), potassium phosphate (1.82 g of,8.58mmol), Pd (dppf) 2Cl2 (176mg, 0.22mmol), dppf (119mg, 0.22mmol), purged with nitrogen, stirred overnight at 100 deg.] C, cooledCooling to room temperature, suction filtered through Celite, and the filtrate was added water (30 mL), dichloromethane (50mL × 6). The organic phase was dried over anhydrous sodium sulfate, filtered sulfurSodium, spin dry the solvent, the residue was purified by column chromatography (dichloromethane: methanol = 50: 1-20: 1 plus ammonia) to give a brown oil (410mg, 51%).

Reference： [1]Patent: CN105254613,2016,A .Location in patent: Paragraph 0295; 0296; 0297

47
[ 1007109-46-7 ]
[ 720702-41-0 ]
C₂₇H₂₈ClF₃N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; N,N-dimethyl-formamide; for 4h;Heating;	General procedure: Pyrimidine-5-boronic acid (212 mg, 1.71 mmol), potassiumcarbonate (236 mg, 1.71 mmol), and tetrakis(triphenylphosphine)palladium(0) (40 mg, 0.035 mmol) were added to asolution of 16 (657 mg, 1.12 mmol) in a mixed solvent ofDMF-EtOH (2 : 1, 10 mL), and the mixture was stirred at90C for 4 h. The reaction mixture was partitioned betweensaturated NaHCO3 aqueous solution and EtOAc, andthe organic layer was washed with water and brine, driedover anhydrous MgSO4, filtered, and concentrated invacuo. The residue was purified using NH-silica gel columnchromatography (20% EtOAc in hexane) to yield a colorlessamorphous solid (237 mg). 1,3-Dimethylbarbituric acid(215 mg, 1.38 mmol) and tetrakis(triphenylphosphine) palladium(0) (5.3 mg, 0.0046 mmol) were added to a solution ofthe amorphous solid in CHCl3 (4 mL), and the mixture wasstirred for 3 h. The reaction mixture was partitioned betweensaturated NaHCO3 aqueous solution and CHCl3, and the organiclayer was dried over anhydrous MgSO4, filtered, andconcentrated in vacuo. The residue was purified using silicagel column chromatography (5% MeOH in CHCl3) and NHsilicagel column chromatography (100% EtOAc) to yield thefree form of 7f (70 mg). 2 mol/L HCl in isopropanol solution(1.0 mL) was added to an ice-cooled solution of the free formof 7f in EtOH (1.0 mL). After concentration in vacuo, theresidue was solidified with EtOAc to yield 7f (59 mg, 10% in2 steps from 16) as a colorless powder.

Reference： [1]Chemical and Pharmaceutical Bulletin,2016,vol. 64,p. 1321 - 1337

48
2-(3-amino-3-oxopropyl)-3’-hydroxy-[1,1‘-biphenyl]-4-yl trifluoromethansulfonate [ No CAS ]
[ 720702-41-0 ]
3-[3'-hydroxy-4-(1-methyl-1H-pyrazol-5-yl)biphenyl-2-yl]propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 4h;Microwave irradiation; Inert atmosphere; Sealed tube;	(C13 A 20 at a csewawa ai wee charged with 213 armna3x prapy0Y* hVd:n?yt?4?v tnd onOan.tnate(03? . OSOJ mntt). tta&5S.ntmic rd (0.17 . I .33 rnrnc and p taethan eatharSe (027 . SSO rnrno0 to a hea at? tdueao (B ml). ethanol (5 ml) and water (1 ml. N?itrogan was haht4ed through the m&we tar 5 ada, batara tetmkirdaenp:hapoh&na&adtom(fl) 10 mat%.. alas g. 0.08 mmd) wee ertded. the reaction. seated and (decal n a rnic;owava reenter tonI h at 120 t. On coding. water (10 ml). .M hdrnnhtada add (10 roll and ath?rl acetate (10 roll wn added. the o?rgadc phase seoarated and the aqoecus plane back .eakacted with et%1 acetate (2 x 10 mU Don?thi:ned cqanlc phaSeS warn dried mser anhrircua mapoesiuro sulphate. tittared tcncSntf ad and the crudemfltoa puatied by lush chnxnotograpltt (eth acattee I dddarcmethana I niethanoh to OI%t P06 0 045 q< 16%) as a ethIc eedd II NMR(400 MHz. DM5041 B 923 (e. I H). 7.45 to. J?a0Hz lH),7A.(d+Js 1.6HZ On. Y19(.dd. J20. 72HZ. It-tI. 7.7?731 ph. 3N. 621 2,76 ph, 211), 616 5,fl pa. 211). 41 4. J 1.8 It 1:H 329 (a.3H. 2,62 (t J 72 Hz, 211), 223 2.25 ph? 2Hl HPLC(waterIACN + 02% TM gfl}de*lt)96.07% at 20 nra; IOMS fMHf?s 322.20,

Reference： [1]Patent: WO2016/145478,2016,A1 .Location in patent: Paragraph 0143

49
N-(4-bromobenzyl)-9H-carbazole-2-carboxamide [ No CAS ]
[ 720702-41-0 ]
N-(4-(1-methyl-1H-pyrazol-5-yl)benzyl)-9H-carbazole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With 1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 100℃; for 12h;Inert atmosphere;	General procedure: To a suspension of 26 (1 equiv), corresponding aryl boronate (1.2 equiv), Pd(dppf)Cl2 (0.05 equiv) and dppf (0.05 equiv) in 1,4-dioxane (2 mL) was added the solution of K3PO4 (2 equiv) in water (0.5 mL). The mixture was stirred at 100 C under N2 for 12 h. After cooling to room temperature, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography(dichloromethane/methanol) to give the desired products 27 and 28.

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 5861 - 5872

50
methyl 6-bromo-5 ,7-dimethyl-4-(trifluoromethylsulfonyloxy)quinoline-2-carboxylate [ No CAS ]
[ 720702-41-0 ]
C₁₇H₁₆BrN₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With tetrakis(triphenylphosphine) palladium(0); triethylamine; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere;	To a mixture of methyl 6-bromo-5 , 7-dimethyl-4-(trifluoromethyl sulfonyloxy)quinoline-2- carboxylate (600 mg, 1.36 mmol), (2-methylpyrazol-3-yl)boronic acid (342 mg, 2.72 mmol), triethylamine (550 mg, 5.44 mmol) in dioxane (15 mL) was added Pd(PPh3)4 (157 mg, 136 .imol) under nitrogen atmosphere. The reaction mixture was stirred at 100 C for 12 hrs. On completion, the reaction mixture was concentrated in vacuo to give the residue. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate = 10:1) to give 104- A (280 mg, 53% yield) as white solid. LCMS (M+1) = 374.0, 376.0.

Reference： [1]Patent: WO2017/27768,2017,A1 .Location in patent: Page/Page column 74

51
[ 1192268-09-9 ]
[ 720702-41-0 ]
[ 1258861-46-9 ]

Reference： [1]MedChemComm,2017,vol. 8,p. 1332 - 1336

52
tert-butyl (1-(4-bromonaphthalen-1-yl)piperidin-4-yl)(methyl)carbamate [ No CAS ]
[ 720702-41-0 ]
C₂₅H₃₂N₄O₂ [ No CAS ]

Reference： [1]MedChemComm,2017,vol. 8,p. 1332 - 1336

53
[ 33443-53-7 ]
[ 720702-41-0 ]
6-(1-methyl-1H-pyrazol-5-yl)-4-phenylquinazolin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 140℃;Microwave irradiation;	General procedure: A mixture of 6-bromo-4-phenylquinazolin-2(1H)-one (200 mg, 0.66 mmol, 1 eq.), DMF (1.5 mL), H2O (0.6 mL), 4-pyridylboronic acid (106 mg, 0.864 mmol, 1.3 eq.), Pd(PPh3)4 (53 mg, 0.046 mmol, 0.07 eq.), and sodium carbonate (162 mg, 1.52 mmol, 2.3 eq.) in a microwave vessel (2 - 5 mL) was heated in the microwave at 140 C for 4 - 24 min. After completion of the reaction (monitored by LC/MS), the mixture was allowed to cool to room temperature, and H2O (8 mL) was added. The resulting precipitate was collected by vacuum filtration and washed with H2O and diethyl ether to afford the crude product as a solid. The crude product was dissolved in a minimal amount of 1,4-dioxane (1 - 10 mL) and any insoluble material was removed by vacuum filtration. A solution of HCl in dioxane (4.0 M) was then added dropwise until a precipitate was formed. The resulting precipitate was collected by vacuum filtration. All Suzuki reactions followed this general procedure, using the appropriate boronic acid, unless otherwise noted.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3629 - 3635

54
[ 33443-53-7 ]
[ 720702-41-0 ]
5-(1-methyl-1H-pyrazol-3-yl)-4-phenylquinazolin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 140℃;Microwave irradiation;	General procedure: A mixture of 6-bromo-4-phenylquinazolin-2(1H)-one (200 mg, 0.66 mmol, 1 eq.), DMF (1.5 mL), H2O (0.6 mL), 4-pyridylboronic acid (106 mg, 0.864 mmol, 1.3 eq.), Pd(PPh3)4 (53 mg, 0.046 mmol, 0.07 eq.), and sodium carbonate (162 mg, 1.52 mmol, 2.3 eq.) in a microwave vessel (2 - 5 mL) was heated in the microwave at 140 C for 4 - 24 min. After completion of the reaction (monitored by LC/MS), the mixture was allowed to cool to room temperature, and H2O (8 mL) was added. The resulting precipitate was collected by vacuum filtration and washed with H2O and diethyl ether to afford the crude product as a solid. The crude product was dissolved in a minimal amount of 1,4-dioxane (1 - 10 mL) and any insoluble material was removed by vacuum filtration. A solution of HCl in dioxane (4.0 M) was then added dropwise until a precipitate was formed. The resulting precipitate was collected by vacuum filtration. All Suzuki reactions followed this general procedure, using the appropriate boronic acid, unless otherwise noted.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3629 - 3635

55
[ 1585-07-5 ]
[ 720702-41-0 ]
5-(4-ethylphenyl)-1-methyl-1H-pyrazole [ No CAS ]