Name: 2458-26-6|3-Phenyl-1H-pyrazole|98%
Brand: Ambeed
SKU: A104401
Price: 5.0 USD
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1
[ 186581-53-3 ]
[ 60-29-7 ]
[ 536-74-3 ]
[ 10199-68-5 ]
[ 2458-26-6 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1958,vol. 614,p. 1

2
[ 186581-53-3 ]
[ 536-74-3 ]
[ 10199-68-5 ]
[ 2458-26-6 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1958,vol. 614,p. 1

3
[ 2458-26-6 ]
[ 59843-36-6 ]

Yield	Reaction Conditions	Operation in experiment
77%	With oxone; sodium chloride In water; ethyl acetate at 20℃; for 1h;	Representative Procedure for Pyrazole Halogenation General procedure: 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole. To a 16 mL vial containing 1-benzyl-3,5-dimethyl-1H-pyrazole (196 mg, 1.05 mmol) and a magnetic stir bar, 0.7 mL of water and 0.3 mL of ethyl acetate was added. Next, NaCl (123 mg, 2 mmol) was added and the vial was placed in a room temperature water bath to control exotherms. Finally, Oxone (322 mg, 0.52 mmol or 1.05 mmol KHSO5) was added and the vial was capped. The reaction proceeded with continuous and vigorous stirring until no starting material remained as indicated by TLC (1 h). The remaining oxidants were reduced with solid sodium bisulfite until starch iodide paper tested negative. Water (5 mL) was added and the mixture was extracted with 1:1 hexanes/diethyl ether (3 x 5 mL). The combined organic fractions were dried (MgSO4) and concentrated to yield crude product that was purified by flash chromatography (14 x 1 cm), 9:1 hexane/ethyl acetate eluent. Pure 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole was obtained as a pale yellow oil (215 mg, 93% yield).
76%	Stage #1: 3-phenylpyrazole With chlorine In tetrachloromethane Stage #2: With sodium carbonate In water
	With sulfuryl dichloride; acetic acid

With N-chloro-succinimide In 1,2-dichloro-ethane at 20℃;

10.10.1 10.1 4-Chloro-3-phenyl-1H-pyrazoleTo a solution of 3-phenyl-1H-pyrazole (3 g, 20.81 mmol) in dichloroethane (60 ml) N-chlorosuccinimide (2.92 g, 21.85 mmol) was added and the mixture was stirred over night at room temperature. The mixture was then concentrated under reduced pressure and the remainder was purified via chromatography on silica gel (eluent: cyclohexane/ethyl acetate 0-30% (v/v)). Concentration of the combined fractions gave 3.54 g of a slightly yellow amorphous solid; ESI-MS [M+H]+: 179.0

Reference： [1]Olsen, Kathryn L.; Jensen, Matthew R.; MacKay, James A. [Tetrahedron Letters, 2017, vol. 58, # 43, p. 4111 - 4114]
[2]Location in patent: experimental part García, M. Ángeles; Cabildo, Pilar; Claramunt, Rosa M.; Pinilla, Elena; Rosario Torres; Alkorta, Ibon; Elguero, José [Inorganica Chimica Acta, 2010, vol. 363, # 7, p. 1332 - 1342]
[3]v. Auwers; Breyhan [Journal fur praktische Chemie (Leipzig 1954), 1935, vol. <2> 143, p. 259,273]
[4]Current Patent Assignee: ABBVIE INC - US2011/152265, 2011, A1 Location in patent: Page/Page column 38

4
[ 2458-26-6 ]
[ 13808-65-6 ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 10 - 35℃; for 1h;	Reference Example 1104-Bromo-3-phenyl-1H-pyrazole A solution of 3-phenyl-1H-pyrazole (4.08 g, 28.3 mmol) and NBS (5.04 g, 28.3 mmol) in DMF (40 mL) was stirred for 1 h at room temperature. The reaction mixture was poured into water and extracted with AcOEt. The extract was washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was recrystallized from hexane/AcOEt to give the title compound (5.84 g, 93% yield) as a white solid: mp 114-116 C.; NMR (300 MHz, CDCl3): delta ppm 7.39-7.50 (31-1, m), 7.64 (1H, s), 7.77 (2H, d, J=6.8 Hz), 10.73 (1H, brs).
91%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;	A solution of 3-phenyl-leta-pyrazole (2.98 g, 20.67 mmol) in anhydrous N,N- dimethylformamide (40 ml) was treated with N-bromosuccinimide (3.68 g, 20.67 mmol) in one portion and then stirred at room temperature for 1 h. The reaction was evaporated under reduced pressure and the resulting residue was dissolved in ethanol (15 ml) and diluted with water (100 ml) to precipitate the crude product. The solids were collected by filtration and dried via air suction. The product was purified by recrystallization from acetonitrile- water to give the title compound (4.19 g, 91 %) as a white solid. MS(ES)+ m/e 224 [M+H]+.
73%	With oxone; sodium bromide; In water; ethyl acetate; at 20℃; for 1h;	General procedure: 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole. To a 16 mL vial containing 1-benzyl-3,5-dimethyl-1H-pyrazole (196 mg, 1.05 mmol) and a magnetic stir bar, 0.7 mL of water and 0.3 mL of ethyl acetate was added. Next, NaCl (123 mg, 2 mmol) was added and the vial was placed in a room temperature water bath to control exotherms. Finally, Oxone (322 mg, 0.52 mmol or 1.05 mmol KHSO5) was added and the vial was capped. The reaction proceeded with continuous and vigorous stirring until no starting material remained as indicated by TLC (1 h). The remaining oxidants were reduced with solid sodium bisulfite until starch iodide paper tested negative. Water (5 mL) was added and the mixture was extracted with 1:1 hexanes/diethyl ether (3 x 5 mL). The combined organic fractions were dried (MgSO4) and concentrated to yield crude product that was purified by flash chromatography (14 x 1 cm), 9:1 hexane/ethyl acetate eluent. Pure 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole was obtained as a pale yellow oil (215 mg, 93% yield).

Reference： [1]Patent: US2010/197651,2010,A1 .Location in patent: Page/Page column 68
[2]Patent: WO2008/150827,2008,A1 .Location in patent: Page/Page column 57
[3]Inorganica Chimica Acta,2010,vol. 363,p. 1332 - 1342
[4]Tetrahedron Letters,2017,vol. 58,p. 4111 - 4114
[5]Chemische Berichte,1895,vol. 28,p. 688
Journal fuer Praktische Chemie (Leipzig),1896,vol. <2> 53,p. 127
[6]Dissertation <Jena 1895>, S. 26,
[7]Journal of Medicinal Chemistry,2015,vol. 58,p. 6766 - 6783

5
(E)-3-(N,N-dimethylamino)-1-phenyl-2-propen-1-one [ No CAS ]
[ 2458-26-6 ]

Yield	Reaction Conditions	Operation in experiment
73%	With hydrazine hydrate In ethanol at 100℃; for 2h;	1 To a stirred solution of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one (2.63 g, 15 mmol) in ethanol (40 ml) was added hydrazine hydrate (1.459 ml, 30.0 mmol). The reaction was heated to 100° C. for 2 hours. Whereupon was cooled to room temperature and ethanol was removed by vacuum. The residue was partitioned between DCM and water. The organic phase was dried over MgSO4 and filtered. After evaporation the crude product was purified by triturating with a mixture of petroleumether and ethyl acetate. (Yield: 1.59 g, 73%).
	With hydrazine hydrate In ethanol for 2h; Heating;
	With hydrazine In ethanol Reflux;

With hydrazine hydrate In ethanol for 2h; Reflux;

D General procedure D for the synthesis of compounds DJ starting from acetophenone (DJ028, DJ029, DJ032) General procedure: A mixture of acetophenone and dimethylformamide dimethylacetal (2.0 equiv.) was refluxed overnight. The reaction mixture was allowed to cool down to room temperature and was concentrated under reduced pressure. The remaining residue was suspended in hexanes and filtered. The filter cake was washed with plenty of hexanes. (E)- 3-(dimethylamino)-l- phenylprop-2-en-l-one was obtained. (0260) Hydrazine-monohydrate (5.0 equiv.) was added to a solution of (E)- 3- (dimethylamino)-l-phenylprop-2-en-l-one in EtOH and the resulting reaction mixture was refluxed for 2 hours. The reaction was then allowed to cool down to room temperature and was concentrated under reduced pressure. The remaining residue was diluted with H2O and extracted with CH2CI2. The organic phase was dried over MgS04, filtered and concentrated under reduced pressure. The residue was considered pure enough by -ΝΜΚ (>95%) to be used without further purification. (0261) A mixture of phenylpyrazole, iodoarene (1.0 equiv.), copper iodide (20 mol%), trans- (0262) 1,2-diaminocyclohexane (25 mol%), potassium carbonate (2.0 equiv.) in dioxane was stirred at 100°C under argon for 16 hours. After cooling down to room temperature, the reaction mixture was diluted with H2O and extracted with EtOAC. The gathered organic phases were washed with NH4CI/NH3 (v/v : 1/1), brine, dried over MgSC , filtered and concentrated under reduced pressure. The remaining residue was purified by column chromatography on silica gel (Hexanes/EtOAc).

Reference： [1]Current Patent Assignee: Bial - Sgps, S.A - US2012/65191, 2012, A1 Location in patent: Page/Page column 30
[2]Pleier; Glas; Grosche; Sirsch; Thiel [Synthesis, 2001, # 1, p. 55 - 62]
[3]Kim, Sung Min; Lee, Seung Woong; Song, Yang-Heon [Bulletin of the Korean Chemical Society, 2014, vol. 35, # 9, p. 2859 - 2862] Kim, Sung Min; Lee, Seung Woong; Song, Yang-Heon [Bulletin of the Korean Chemical Society, 2014, vol. 35, # 9, p. 2859 - 2862]
[4]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2017/205795, 2017, A1 Location in patent: Page/Page column 36-37

6
[ 2458-26-6 ]
[ 28791-97-1 ]
[ 3347-62-4 ]
C₂₀H₂₂N₆ [ No CAS ]
C₂₁H₂₄N₆ [ No CAS ]
C₂₅H₂₄N₆ [ No CAS ]
C₂₆H₂₆N₆ [ No CAS ]

Reference： [1]Tetrahedron Letters,2001,vol. 42,p. 5 - 7

7
[ 288-13-1 ]
[ 591-50-4 ]
[ 2458-26-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	With palladium diacetate; magnesium oxide; triphenylphosphine In 1,4-dioxane at 150℃;

Reference： [1]Sezen, Bengue; Sames, Dalibor [Journal of the American Chemical Society, 2003, vol. 125, # 18, p. 5274 - 5275]

8
[ 108-86-1 ]
[ 376584-63-3 ]
[ 2458-26-6 ]

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

9
[ 2458-26-6 ]
[ 105994-77-2 ]

Reference： [1]Chemische Berichte,1925,vol. 58,p. 537

10
sulfimidate [ No CAS ]
[ 2458-26-6 ]
[ 207557-35-5 ]
(2S)-1-[(1S)-1-Methyl-2-(3-phenyl-pyrazol-1-yl)-ethylamino]-acetyl}-pyrrolidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 108 (2S)-1-[(1S)-1-Methyl-2-(3-phenyl-pyrazol-1-yl)-ethylamino]-acetyl}-pyrrolidine-2-carbonitrile Synthesis of this compound required the preparation of amines IIIM, that can be prepared as described for the pyrazoles IIIH, triazoles IIIK and imidazols IIIL by replacing sulfimidate XIX with sulfimidate IV. Starting pyrazols XXII, [1,2,4]triazoles XXVI and imidazols XXVIII used in examples 108-112 are commercially available, are known or are prepared as described in the previous examples or in the individual examples that follow. Regioisomers (e.g. XXX-A) may be formed that are isolated individually, deprotected by acid treatment to give amines IIIM. Amines IIIM are subsequently used in the final coupling step with IIA to furnish cyanopyrrolidines I. The above title compound was obtained in analogy to example 78, steps C] to E] by replacing 5-methyl-3-phenyl-1H-pyrazole with commercially available 3-phenyl-1H-pyrazole and by replacing sulfimidate XIX with IV and with the exception, that the final coupling step with IIA was done as described in example 1. The title compound was obtained as the free amine as a glass. MS (ISP): 338.3 (MH+).

Reference： [1]Patent: US2003/130281,2003,A1

11
[ 2458-26-6 ]
[ 824-94-2 ]
[ 929918-61-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate In butanone for 24h; Heating / reflux;	154.1 EXAMPLE 154; Step 1; 1-(4-Methoxy-benzyl)-3-phenyl-1H-pyrazole; A mixture of 3-phenyl-1H-pyrazole (1.35 g, 9.36 mmol), 4-methoxybenzyl chloride (1.5 g, 9.7 mmol) and K2CO3 (3.3 g, 24.2 mmol) in methyl ethyl ketone was refluxed for 24 h. The salts were filtered off, and the solvent was removed in vacuo. The residue was purified by a column chromatography on silica gel to yield the title compound (2.2 g, 89%).

Reference： [1]Current Patent Assignee: AMGEN INC - US2007/66820, 2007, A1 Location in patent: Page/Page column 81

12
[ 12257-42-0 ]
[ 2458-26-6 ]
[Rh(NBD)(μ-5-phenylpyrazolate)]2 [ No CAS ]

Reference： [1]Journal of Organometallic Chemistry,1996,vol. 511,p. 115 - 127

13
[ 1033804-98-6 ]
[ 2458-26-6 ]
[ 1033805-07-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In toluene at 130℃; for 12h;	6.15 6.15. Synthesis of (S)-2-Amino-3-[4-(2-amino-6-{2,2,2-trifluoro-1-[2-(3-phenyl-pyrazol-1-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-propionic acid 2,2,2-Trifluoro-1-(2-iodo-phenyl)-ethanol (0.331 g, 1.1 mmol), 3-phenyl pyrazole (0.144 g, 1.0 mmol), CuI (0.019 g, 0.1 mmol), K2CO3 (0.290 g, 2.1 mmol), (1R,2R)-N,N'-dimethyl-cyclohexane-1,2-diamine (0.028 g, 0.2 mmol) and toluene (10 ml) were taken in a 20 ml pressure tube and the mixture was heated at 130° C. (oil bath temperature) for 12 h. The mixture was diluted with ethyl acetate and washed with H2O (2*20 ml), brine, and dried over sodium sulfate. Removal of solvent gave a crude product, which was purified by ISCO column chromatography using 5-10% ethyl acetate in hexane as solvent to afford 2,2,2-trifluoro-1-[2-(3-phenyl-pyrazol-1-yl)-phenyl]-ethanol (75 mg).
75 mg	With (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane In toluene at 130℃; for 12h;	15 A solution of 2,2,2-trifluoro-1- (2-iodo-phenyl) -ethanol (0.331 g, 1.1 mmol), 3-phenylpyrazole (0.144 g,(0.1 L), (1R, 2R) -N, N'-dimethyl-cyclohexane-1,2-diamine (0.028 g, 0.2 mmol) and toluene (10 ml) were placed in a 20 ml pressure tube at 130 ° C (oil bath temperature)Under heating for 12 hours. The mixture was diluted with ethyl acetate, washed with H? O (2 x 20 ml), brine and dried over sodium sulfate. RemovedSolvent The crude product was purified by ISCO column chromatography using 5-10% ethyl acetate in hexanes as solvent to giveTo a solution of 2,2,2-trifluoro-1- [2- (3-phenyl-pyrazol-1-yl) -phenyl] -ethanol (75 mg).

Reference： [1]Current Patent Assignee: GTCR LLC - US2008/153852, 2008, A1 Location in patent: Page/Page column 16
[2]Current Patent Assignee: LEXICON PHARMACEUTICALS INC - CN104045626, 2017, B Location in patent: Paragraph 0207

14
[ 2458-26-6 ]
[ 85953-29-3 ]
[ 530091-45-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 9524 - 9535

15
[ 26976-72-7 ]
[ 2458-26-6 ]
acetic acid 4-oxo-4-(3-phenyl-pyrazol-1-yl)-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	Stage #1: 4-acetoxybutyric acid With isopropyl chloroformate; triethylamine In tetrahydrofuran at 0 - 5℃; for 0.833333h; Stage #2: 3-phenylpyrazole In tetrahydrofuran at 20℃; for 48h;	7 To a stirred solution of 0.5 g (3.5 mmol) of 4-acetoxy-butyric acid (IV) in 35 mL of THF was added 0.42g (4.1 mmol) of triethylamine at 0-5 0C. After five minutes, 0.56 g (4.1 mmol) of isopropyl chloroformate was added slowly. The mixture was then stirred at this temperature for 45 minutes. A solution of 0.59 g (4.1 mmol) of 3 -phenyl- IH- pyrazole in 5 mL of THF was added to the mixture. After it was stirred at room temperature for 2 days, 100 mL of ethyl acetate was added, followed by washing with water (2 X 15 mL). The ethyl acetate solution was dried over sodium sulphate, concentrated and purified (silica gel, 7:1 hexanes/EtOAc) to afford 0.55 g (59%) of (V). 1H NMR (DMSO-d6, 300 MHz): δ 8.49 (d, J=3.5, IH); 7.98-7.94 (m, 2H); 7.52- 7.41 (m, 3H); 7.17(d, J=3, IH); 4.13(t, J=6.3 Hz5 2H); 3.27(t, J=7.35 2H); 2.03(q, J=7.1 Hz5 2H); 1.98 (s, 3H). Anal. Calcd. for (C15H16N2O3): C5 66.16; H5 5.92; N5 10.29. Found: C5 66.10; H, 6.00; N, 10.29.

Reference： [1]Current Patent Assignee: WU, Yong-Qian; HAMILTON, Gregory, S.; BELYAKOV, Sergei; WALDON, Daniel - WO2006/138187, 2006, A1 Location in patent: Page/Page column 38

16
[ 2458-26-6 ]
C₁₈H₁₄N₄OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-phenylpyrazole With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: With thionyl chloride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;
	Stage #1: 3-phenylpyrazole With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: With thionyl chloride In tetrahydrofuran at 20℃; for 0.0833333h;	3.2. Synthesis of 1(Ph) 3-Phenylpyrazole (2.00 g, 13.87 mmol) as a solid was added to a stirred slurry of NaH (0.33 g, 13.87 mmol) in THF (60 mL) at r.t. After 30 min SOCl2 (0.50 mL, 0.83 g, 6.94 mmol) was added in one portion via syringe and the resulting mixture stirred at r.t. for 5 min. After addition of 3,4-dihydroxybenzaldehyde (0.96 g, 6.94 mmol) and pyridine (5.60 mL, 4.78 g, 60.40 mmol), the reaction mixture was kept at reflux temperature for 16 h. H2O (50 mL) was added and the aqueous phase extracted into CH2Cl2 (3 × 50 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered, and the filtrate was evaporated to dryness in vacuo. The crude product was purified by column chromatography (silica gel; CHCl3/EtOAc 1:1). All product-containing fractions were concentrated by rotary evaporation at 40 °C and upon cooling to r.t. colorless 1(Ph) precipitated, which was isolated by filtration and washed with Et2O. Yield: 1.53 g (54%). Rf = 0.63 (silica gel, CHCl3/EtOAc 1:1). 1H NMR (400.1 MHz, d6-DMSO) δ = 6.48 (dd, 3JHH = 8.3, 4JHH = 2.0, 1 H; HQ-H6), 6.66 (d, 4JHH = 2.0, 1 H; HQ-H2), 6.76 (d, 3JHH = 8.3, 1 H; HQ-H5), 6.84 (d, 3JHH = 2.5, 2 H; pz-H4), 7.31 (m, 2 H; Ph-H4), 7.41 (m, 4 H; Ph-H3), 7.82 (m, 4 H; Ph-H2), 7.91 (s, 1 H; CH), 7.94 (d, 3JHH = 2.5, 2 H; pz-H5), 9.15 (bs, 2 H; OH). 13C NMR (100.6 MHz, d6-DMSO) δ = 76.7 (Cpz2), 103.5 (pz-C4), 114.4 (HQ-C2), 115.5 (HQ-C5), 118.2 (HQ-C6), 125.3 (Ph-C2), 127.2 (HQ-C1), 127.8 (Ph-C4), 128.7 (Ph-C3), 131.9 (pz-C5), 132.8 (Ph-C1), 145.3, 146.1 (HQ-C3,4), 151.0 (pz-C3). ESI-MS: m/z (%) 263 (67) [M - Phpz]-, 408 (100) [M - H]-. Anal. Calcd (%) for C25H20N4O2 (408.45): C 73.51, H 4.94, N 13.72. Found: C 73.22, H 4.86, N 13.67.

Reference： [1]Location in patent: experimental part Blasberg, Florian; Bats, Jan W.; Bolte, Michael; Lerner, Hans-Wolfram; Wagner, Matthias [Inorganic Chemistry, 2010, vol. 49, # 16, p. 7435 - 7445]
[2]Location in patent: experimental part Blasberg, Florian; Bolte, Michael; Wagner, Matthias; Lerner, Hans-Wolfram [Journal of Organometallic Chemistry, 2011, vol. 696, # 23, p. 3593 - 3600]

17
[ 591-50-4 ]
[ 2458-26-6 ]
[ 4492-01-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With copper(II) acetate monohydrate; caesium carbonate In N,N-dimethyl-formamide at 110℃; for 24h; Inert atmosphere; regioselective reaction;	4.6. General catalytic procedure for the N-arylation of nitrogen-containing heterocycles with aryl iodides General procedure: To a solution of Cu(OAc)2·H2O (0.01 mmol) in DMF (2 mL) were added aryl iodide (1.2 mmol), nitrogen-containing heterocycle (1.0 mmol), and Cs2CO3 (2 mmol) under nitrogen atmosphere. The mixture was stirred at 110 °C for 24 h. After cooling to ambient temperature, the mixture was partitioned between water and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel.
62%	With copper(l) iodide; potassium carbonate; dimethyl sulfoxide; glycerol at 120℃; for 24h;	General experimental procedure General procedure: To a 25 ml two-necked round-bottom flask was placed a mixture of aryl iodide (1 mmol), indole (1.5 mmol), CuI (0.1 mmol), K2CO3 (2 mmol), and DMSO (1 mmol) in 2 ml glycerol. The reaction mixture was heated in an oil bath at 120°C for 24 h with continuous stirring. After completion of reaction monitored by TLC, the reaction mixture was cooled to room temperature and was extracted with diethyl ether three times (3×10 ml). The combined organic layers were washed with brine solution and dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (60-120 mesh) to provide the N-aryl indole in 88% yield. The remaining glycerol/copper catalytic mixture was reused for further recycling study by adding fresh DMSO (1 mmol) to the catalytic system. All the products are well known in the literature and were confirmed by comparison of their spectroscopic data with literature data.
62%	With copper(l) iodide; potassium carbonate; dimethyl sulfoxide In ethylene glycol at 120℃; for 24h; Green chemistry;	General experimental procedure: General procedure: To a 25ml two-necked round-bottom flask was placed a mixture of aryl iodide (1mmol), indole (1.5mmol), CuI (0.1mmol), K2CO3 (2mmol), and DMSO (1mmol) in 2ml glycerol. The reaction mixture was heated in an oil bath at 120°C for 24h with continuous stirring. After completion of reaction monitored by TLC, the reaction mixture was cooled to room temperature and was extracted with diethyl ether three times (3×10ml). The combined organic layers were washed with brine solution and dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (60-120 mesh) to provide the N-aryl indole in 88% yield. The remaining glycerol/copper catalytic mixture was reused for further recycling study by adding fresh DMSO (1mmol) to the catalytic system. All the products are well known in the literature and were confirmed by comparison of their spectroscopic data with literature data.

With copper(l) iodide; potassium carbonate; trans-1,2-cyclohexanediamine In 1,4-dioxane at 100℃; for 16h; Inert atmosphere;

D General procedure D for the synthesis of compounds DJ starting from acetophenone (DJ028, DJ029, DJ032) General procedure: A mixture of acetophenone and dimethylformamide dimethylacetal (2.0 equiv.) was refluxed overnight. The reaction mixture was allowed to cool down to room temperature and was concentrated under reduced pressure. The remaining residue was suspended in hexanes and filtered. The filter cake was washed with plenty of hexanes. (E)- 3-(dimethylamino)-l- phenylprop-2-en-l-one was obtained. (0260) Hydrazine-monohydrate (5.0 equiv.) was added to a solution of (E)- 3- (dimethylamino)-l-phenylprop-2-en-l-one in EtOH and the resulting reaction mixture was refluxed for 2 hours. The reaction was then allowed to cool down to room temperature and was concentrated under reduced pressure. The remaining residue was diluted with H2O and extracted with CH2CI2. The organic phase was dried over MgS04, filtered and concentrated under reduced pressure. The residue was considered pure enough by -ΝΜΚ (>95%) to be used without further purification. (0261) A mixture of phenylpyrazole, iodoarene (1.0 equiv.), copper iodide (20 mol%), trans- (0262) 1,2-diaminocyclohexane (25 mol%), potassium carbonate (2.0 equiv.) in dioxane was stirred at 100°C under argon for 16 hours. After cooling down to room temperature, the reaction mixture was diluted with H2O and extracted with EtOAC. The gathered organic phases were washed with NH4CI/NH3 (v/v : 1/1), brine, dried over MgSC , filtered and concentrated under reduced pressure. The remaining residue was purified by column chromatography on silica gel (Hexanes/EtOAc).

Reference： [1]Xu, Zhong-Lin; Li, Hong-Xi; Ren, Zhi-Gang; Du, Wei-Yuan; Xu, Wei-Chang; Lang, Jian-Ping [Tetrahedron, 2011, vol. 67, # 29, p. 5282 - 5288]
[2]Yadav, Dilip Kumar T.; Rajak, Sanil S.; Bhanage, Bhalchandra M. [Tetrahedron Letters, 2014, vol. 55, # 4, p. 931 - 935]
[3]Yadav, Dilip Kumar T.; Rajak, Sanil S.; Bhanage, Bhalchandra M. [Tetrahedron Letters, 2014, vol. 55, # 4, p. 931 - 935]
[4]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2017/205795, 2017, A1 Location in patent: Page/Page column 36-37

18
[ 104-55-2 ]
[ 2458-26-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With iodine; potassium carbonate; toluene-4-sulfonic acid hydrazide In ethanol at 75℃; for 2h; Green chemistry; regioselective reaction;	2. Experimental procedure for the preparation of pyrazoles General procedure: To a stirred mixture of α,β-unsaturated aldehydes/ketones 1 (0.5 mmol) and TsNHNH2 (0.6 mmol) in EtOH (2.0 ml) was added molecular iodine (2.5 mg, 2 mol%) in an oven-dried flask, and then the reaction was heated to 75 °C for 10 min followed by the addition of K2CO3 immediately. The reaction proceeded under an air atmosphere for 1.5-2.0 h until complete consumption of starting material as monitored by TLC. The reaction mixture was concentrated under vacuum and the crude product was purified by column chromatography using petroleum ether/ethyl acetate as eluent to provide the product 2.
94%	With tetrabutylammomium bromide; toluene-4-sulfonic acid hydrazide; sodium hydroxide In water at 80℃; for 10h; Air atmosphere;	4.3. General procedure for the substituted benzylidenacetone General procedure: A Schlenk tube with a magnetic stir bar charged with α,β-unsaturated carbonyl compounds (0.5 mmol, 1 equiv), tosyl hydrazide (0.6 mmol, 1.2 equiv), NaOH (1.5 equiv), (n-Bu)4NBr (1.5 equiv). The reaction vessel was placed in an 80 °C oil bath, and then stirring at this temperature for 10 h. The reaction mixture was then allowed to cool to ambient temperature, and diluted with 20 mL of ethyl acetate, and washed with brine (15 mL), water (15 mL), and then the organic layer was dried over Na2SO4. After concentrated in vacuo, the crude product was purified by column chromatography. The identity and purity of the known product was confirmed by 1H NMR, 13C NMR, and GC-MS.
89%	With tetrabutylammomium bromide; toluene-4-sulfonic acid hydrazide; sodium hydroxide In water for 10h; Inert atmosphere; Schlenk technique; Reflux;

Multi-step reaction with 2 steps 1: methanol / 0.5 h / 60 °C 2: caesium carbonate / 1,4-dioxane / 4 h / 90 °C

Reference： [1]Zhang, Hailei; Wei, Qian; Zhu, Guodong; Qu, Jingping; Wang, Baomin [Tetrahedron Letters, 2016, vol. 57, # 24, p. 2633 - 2637]
[2]Wen, Jun; Fu, Yun; Zhang, Ruo-Yi; Zhang, Ji; Chen, Shan-Yong; Yu, Xiao-Qi [Tetrahedron, 2011, vol. 67, # 49, p. 9618 - 9621]
[3]Liang, Dong; Chen, Xu-Lin; Liao, Jian-Zhen; Hu, Jin-Yu; Jia, Ji-Hui; Lu, Can-Zhong [Inorganic Chemistry, 2016, vol. 55, # 15, p. 7467 - 7475]
[4]Chen, Lian-Mei; Zhao, Juan; Xia, An-Jie; Guo, Xiao-Qiang; Gan, Ya; Zhou, Chuang; Yang, Zai-Jun; Yang, Jun; Kang, Tai-Ran [Organic and Biomolecular Chemistry, 2019, vol. 17, # 37, p. 8561 - 8570]

19
[ 1333146-86-3 ]
[ 2458-26-6 ]
[ 1333147-09-3 ]

Yield	Reaction Conditions	Operation in experiment
54%	With copper(l) iodide; potassium carbonate; cis-N,N'-dimethyl-1,2-diaminocyclohexane In 1,4-dioxane at 20 - 110℃;	7 3-(Benzyloxy)-l-methyl-5-(3-phenyI-lH-pyrazol-l-yl)pyridin-2(lH)-3-(Benzyloxy)-5-bromo-l-methylpyridin-2(lH)-one (50 mg, 0.170 mmol), 3-phenyl-lH-pyrazole (29 mg, 0.201 mmol), K2C03 (47.0 mg, 0.340 mmol), Cul (2 mg, 10.50 μϖιο), and N, imethyM,2- cyclohexanediamine (6 μ, 0.038 mmol) were combined in 1,4-dioxane (0.5 mL) in a screw cap vial. The vial was sealed then heated to 110 °C. After stirring overnight the mixture was cooled to RT. Cul (2 mg) and N,N'-dimethyl-l,2-cyclohexanediamine (6 uL) were added and heating continued at 1 10 °C. After stirring overnight the mixture was cooled to RT and diluted with EtOAc. The resulting mixture was filtered and concentrated. The crude material was purified by preparative reversed-phase HPLC (20x150mm Waters Sunfire (0.1% TFA), 5- 70% CH3CN/water over 20 min at 20 mL/min) to give the title compound (33 mg, 54%) as an amber film. fH NMR (500 MHz, CDCI3): δ 7.85 (d, J = 7.7 Hz, 2 H); 7.61 (d, J = 2.5 Hz, 1 H); 7.50-7.32 (m, 9 H); 7.12 (d, J = 2.6 Hz, 1 H); 6.73 (d, J - 2.5 Hz, 1 H); 5.21 (s, 2 H); 3.68 (s, 3 H). LC MS (M+H)+ 358.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2011/109261, 2011, A1 Location in patent: Page/Page column 43-44

20
[ 2458-26-6 ]
[ 74-88-4 ]
[ 3463-26-1 ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: 3-phenylpyrazole With sodium hydride In tetrahydrofuran; mineral oil for 1h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 20℃; for 18h;	42 Examples 42-48Preparation of N-(2,6-difluorophenyl)[5-(1-methyl-3-phenylpyrazol-5-yl](2-thienyl)}carboxamide (93) To a solution of 90 (1 g, 6.9 mmol) in THF (50 mL) was added NaH (0.66 g, 27.6 mmol). The mixture was stirred for 1 h and the MeI (1.97 g, 13.8 mmol) was added in one potion. The reaction mixture was stirred for 18 h at room temperature. The reaction was quenched with MeOH and solvent was removed in vacuo. The residue was treated with water and EtOAc. The organic layer was separated and aqueous was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, concentrated to give crude product. The crude product was purified on ISCO columns. Fractions containing pure product were combined and evaporated. The yellow oil 91 (0.53 g, 48%) was obtained.

Reference： [1]Current Patent Assignee: CALCIMEDICA, INC. - US2012/53210, 2012, A1 Location in patent: Page/Page column 76

21
[ 2458-26-6 ]
[ 588-63-6 ]
[ 1389791-60-9 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 3-phenylpyrazole With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 60℃; for 2h; Inert atmosphere; Stage #2: 3-phenoxypropyl bromide In tetrahydrofuran; N,N-dimethyl-formamide at 60℃; for 24h; Inert atmosphere;	Synthesis of the phenyl ether-pyrazolyl ligands General procedure: 3,5-dimethyl-1-(3-phenoxypropyl)-1H-pyrazole (L1): A solution of 3,5-dimethyl-1H-pyrazole (0.30 g, 3.2 mmol) in DMF/THF (v/v = 1:1, 12 mL) was added to a suspension of NaH (0.15 g, 6.4 mmol) in DMF/THF (v/v = 2:1, 15 mL) and stirred at 60 °C for 2 h. Then, the resulting solution was added under stirring to a solution of 3-bromopropyl phenyl ether (0.70 g, 3.2 mmol) in DMF (7 mL). The mixture was allowed to stir for 24 h at 60 °C, cooled, and treated cautiously with H2O (5 mL) to decompose excess NaH. The solvents were then evaporated under reduced pressure. The residue was extracted with ethyl acetate (3 * 15 mL), washed with H2O (2 * 15 mL). The organic phase was dried over MgSO4 and filtered, before the solvent was evaporated under reduced pressure. After workup and purification by chromatographic column on silica gel (hexane/ethyl acetate, 90:10), L1 was obtained as a colorless oil (0.47 g, 64%).

Reference： [1]Ulbrich, Ana H.D.P.S.; Campedelli, Roberta R.; Milani, Jorge L. Sônego; Santos, João H.Z. Dos; Casagrande, Osvaldo De L. [Applied Catalysis A: General, 2013, vol. 453, p. 280 - 286]

22
[ 108-86-1 ]
[ 133228-21-4 ]
[ 2458-26-6 ]

Reference： [1]Advanced Synthesis and Catalysis,2014,vol. 356,p. 1555 - 1561

23
[ 109-99-9 ]
[ 2458-26-6 ]
3-phenyl-1-(tetrahydrofuran-2-yl)-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With tetrabutylammonium tetrafluoroborate In acetonitrile at 80℃; for 5h; Electrochemical reaction; Inert atmosphere;
82%	With 9-(2-mesityl)-10-methylacridinium perchlorate at 20℃; for 24h; Schlenk technique; Irradiation;
57%	With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water; 1,2-dichloro-ethane at 80℃; for 12h;

Reference： [1]Wu, Jiwei; Zhou, Yi; Zhou, Yuchen; Chiang, Chien-Wei; Lei, Aiwen [ACS Catalysis, 2017, vol. 7, # 12, p. 8320 - 8323]
[2]Zhang, Lingling; Yi, Hong; Wang, Jue; Lei, Aiwen [Journal of Organic Chemistry, 2017, vol. 82, # 19, p. 10704 - 10709]
[3]Aruri, Hariprasad; Singh, Umed; Sharma, Sumit; Gudup, Satish; Bhogal, Mukesh; Kumar, Sanjay; Singh, Deepika; Gupta, Vivek K.; Kant, Rajni; Vishwakarma, Ram A.; Singh, Parvinder Pal [Journal of Organic Chemistry, 2015, vol. 80, # 3, p. 1929 - 1936]

24
[ 7318-33-4 ]
[ 2458-26-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With water; potassium carbonate; diethylamine In acetonitrile at 120℃; for 24h; Green chemistry;
95%	With caesium carbonate In 1,4-dioxane at 90℃; for 4h;

Reference： [1]Xiong, Wenfang; Qi, Chaorong; He, Haitao; Ouyang, Lu; Zhang, Min; Jiang, Huanfeng [Angewandte Chemie - International Edition, 2015, vol. 54, # 10, p. 3084 - 3087][Angew. Chem., 2015, vol. 127, # 10, p. 3127 - 3130,4][Angewandte Chemie, 2015, vol. 127, # 10, p. 3127 - 3130,4]
[2]Chen, Lian-Mei; Zhao, Juan; Xia, An-Jie; Guo, Xiao-Qiang; Gan, Ya; Zhou, Chuang; Yang, Zai-Jun; Yang, Jun; Kang, Tai-Ran [Organic and Biomolecular Chemistry, 2019, vol. 17, # 37, p. 8561 - 8570]

25
[ 2458-26-6 ]
[ 112633-26-8 ]
[ 450342-30-0 ]

Yield	Reaction Conditions	Operation in experiment
40%	Stage #1: 3-phenylpyrazole With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Inert atmosphere; Stage #2: 2,6-bis[(tosyloxy)methyl]pyridine In tetrahydrofuran at 25℃; Inert atmosphere;	1 Preparation of 2,6-bis[(3-phenyl-1H-pyrazol-1-yl)methyl]pyridine (L4) At 0 °C, a solution of 3-phenyl-1H-pyrazole (0.61 g, 5.3 mmol) in dry THF (10 mL) was added dropwise to a suspension of NaH (0.13 g,5.34 mmol) in dry THF (10 mL). After 15 min of stirring, a solution of 2,6-pyridine-dimethylene-ditosylate (1.20 g, 2.67 mmol) in dry THF (15 mL) was added to this solution; the mixture was stirred overnight and filtered, and the solvent was removed. The crude product was purified by column chromatography on silica gel with hexane:EA = 1:1 as eluent to afford 0.41 g (40%) of pure ligand as a white oil that solidified with time. Single crystals were obtained by slow diffusion of hexane into a concentrated solution of the ligand in THF at room temperature. 1H NMR (300 MHz, acetone-d6): 7.84(m, 2H, 4H, 5-H Pz, 2,6-H Ph), 7.65 (t, J = 7.8 Hz, 1H, 4-H Py), 7.36(t, J = 7.2 Hz, 4H, 3,5-H Ph), 7.26 (t, J = 7.5 Hz, 2H, 4-H Ph), 6.96 (d,J = 7.8 Hz, 2H, 3,5-H Py), 6.72 (d, J = 2.4 Hz, 2H, 4-H Pz), and 5.48 (s,4H, PyCH2Pz).13C NMR (75 MHz, acetone-d6): 157.9 (2C, 2,6-CPy), 152.2 (2C, 3-C Pz), 138.9 (1C, 4-C Py), 134.8 (2C, 1-C Ph), 132.9(2C, 5-C Pz), 129.3(4C, 3,5-C Ph), 128.2 (2C, 4-C Ph), 126.1 (4C, 2,6-CPh), 121.2 (2C, 3,5-C Py), 103.7 (2C, 4-C Pz), and 57.9 (2C, PyCH2Pz).

Reference： [1]Woo, Jeong Oh; Kang, Sung Kwon; Park, Jong-Eun; Son, Kyung-Sun [Journal of Molecular Catalysis A: Chemical, 2015, vol. 404-405, p. 204 - 210]

26
[ 14521-80-3 ]
[ 98-80-6 ]
[ 2458-26-6 ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6766 - 6783

27
[ 2458-26-6 ]
[ 292638-85-8 ]
methyl 3-(3-phenyl-1H-pyrazol-1-yl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 50℃; for 18h; Inert atmosphere;	9 Methyl 3-(3-phenyl- 1 H -pyrazol- 1 -yljpropanoate General procedure: Methyl 3-(3-phenyl- 1 H -pyrazol- 1 -yljpropanoate Synthesised using the general procedure for Michael addition. General Synthetic Procedures and Characterisation Michael Addition 3-Phenyl-1 H-pyrazole (1 .73 mmol), acrylate (5.20 mmol) and DBU (130 μΙ, 0.87 mmol) were combined in acetonitrile (3.5 ml), under nitrogen. The reaction was stirred at 50 °C for 18 h and monitored by TLC. Once complete all of the volatiles were removed in vacuo and the crude material was purified by column chromatography, eluting with 15-25% ethyl acetate/petroleum spirits to obtain the desired product. Methyl 3-(3-phenyl- 1 H -pyrazol- 1 -yljpropanoate Synthesised using the general procedure for Michael addition.
73%	Stage #1: 3-phenylpyrazole With potassium carbonate In N,N-dimethyl-formamide for 0.5h; Stage #2: acrylic acid methyl ester In N,N-dimethyl-formamide for 48h;

Reference： [1]Current Patent Assignee: MONASH UNIVERSITY; UNIVERSITY OF WESTERN AUSTRALIA - WO2015/172196, 2015, A1 Location in patent: Page/Page column 0032; 00130; 00151
[2]Varghese, Swapna; Rahmani, Raphaël; Russell, Stephanie; Deora, Girdhar Singh; Ferrins, Lori; Toynton, Arthur; Jones, Amy; Sykes, Melissa; Kessler, Albane; Eufrásio, Amanda; Cordeiro, Artur Torres; Sherman, Julian; Rodriguez, Ana; Avery, Vicky M.; Piggott, Matthew J.; Baell, Jonathan B. [ACS Medicinal Chemistry Letters, 2019, p. 278 - 285]

28
[ 2458-26-6 ]
[ 80-62-6 ]
methyl 2-methyl-3-(3-phenyl-1H-pyrazol-1-yl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 50℃; for 20h; Inert atmosphere;	Methyl 2-methyl-3-(3-phenyl-1H-pyrazol- 1 -yljpropanoate Methyl 2-methyl-3-(3-phenyl-1H-pyrazol- 1 -yljpropanoate 3-Phenyl-1 H-pyrazole (250 mg, 1 .73 mmol), methyl methacrylate (280 μΙ, 2.60 mmol) and DBU (130 μΙ, 0.87 mmol) were combined in acetonitrile (3.5 ml), under nitrogen. The reaction was stirred at 50 °C for 18 h, though by TLC there was only a 50% conversion of the starting material to product. Additional methyl methacrylate (280 μΙ, 2.60 mmol) added to the reaction, and returned to heat at 50 °C for an additional 2 h. By TLC the reaction was complete and all volatiles were removed in vacuo and the crude material was purified by column chromatography, eluting 15-25% ethyl acetate/petroleum spirits. The title compound was obtained as a colourless oil (342 mg, 81 %). LRMS [M+H]+ 245.2 m/z; HRMS [M+H]+ 245.1285 m/z, found 245.1284 m/z; 1H NMR (400 MHz, DMSO) δ 7.76 (ddd, J= 9.8, 6.3, 1 .8 Hz, 3H), 7.44 - 7.33 (m, 2H), 7.29 (dt, J = 9.3, 4.3 Hz, 1 H), 6.68 (d, J = 2.3 Hz, 1 H), 4.37 (dd, J = 13.6, 7.1 Hz, 1 H), 4.25 (dd, J= 13.6, 6.4 Hz, 1 H), 3.61 (s, 3H), 3.06 (dd, J= 13.7, 7.0 Hz, 1 H), 1 .06 (d, J = 7.1 Hz, 3H).
81%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 50℃; for 20h; Inert atmosphere;

Reference： [1]Current Patent Assignee: MONASH UNIVERSITY; UNIVERSITY OF WESTERN AUSTRALIA - WO2015/172196, 2015, A1 Location in patent: Page/Page column 00157
[2]Varghese, Swapna; Rahmani, Raphaël; Russell, Stephanie; Deora, Girdhar Singh; Ferrins, Lori; Toynton, Arthur; Jones, Amy; Sykes, Melissa; Kessler, Albane; Eufrásio, Amanda; Cordeiro, Artur Torres; Sherman, Julian; Rodriguez, Ana; Avery, Vicky M.; Piggott, Matthew J.; Baell, Jonathan B. [ACS Medicinal Chemistry Letters, 2019, p. 278 - 285]

29
[ 623-43-8 ]
[ 2458-26-6 ]
methyl 3-(3-phenyl-1H-pyrazol-1-yl)butanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 50℃; for 18h; Inert atmosphere;	Methyl 3-(3-phenyl- 1 H -pyrazol- 1 -yl)butanoate Methyl 3-(3-phenyl- 1 H -pyrazol- 1 -yl)butanoate 3-Phenyl-1 H-pyrazole (250 mg, 1 .73 mmol), methyl crotonate (275 μΙ, 2.60 mmol) and DBU (130 μΙ, 0.87 mmol) were combined in acetonitrile (3.5 ml), under nitrogen. The reaction was stirred at 50 °C for 18 h and by TLC the reaction was complete. All of the volatiles were removed in vacuo and the crude material was purified by column chromatography, eluting 15-25% ethyl acetate/petroleum spirits. The title compound was obtained as a colourless oil [32] mg, 76%). HPLC - rt 7.48 min > 98% purity at 254 nm; LRMS [M+H]+ 245.2 m/z; HRMS [M+H]+ 245.1285 m/z, found 245.1284 m/z; 1 H NMR (400 MHz, DMSO) δ 7.87 - 7.70 (m, 3H), 7.44 - 7.33 (m, 2H), 7.33 - 7.19 (m, 1 H), 6.66 (d, J = 2.3 Hz, 1 H), 4.93 - 4.62 (m, 1 H), 3.56 (s, 3H), 2.93 (ddd, J= 22.0, 16.0, 7.0 Hz, 2H), 1 .48 (d, J = 6.8 Hz, 3H); 13C NMR (101 MHz, DMSO) δ 170.8, 149.7, 133.5, 130.3, 128.6 (2C), 127.3, 125.0 (2C), 102.2, 54.0, 51 .5, 40.5, 20.9.

Reference： [1]Current Patent Assignee: MONASH UNIVERSITY; UNIVERSITY OF WESTERN AUSTRALIA - WO2015/172196, 2015, A1 Location in patent: Page/Page column 00162

30
[ 2458-26-6 ]
[ 126301-16-4 ]
tert-butyl (S)-(1-(3-phenyl-1H-pyrazol-1-yl)propan-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 3h;	Tert-butyl (S)-(1 -(3-phenyl-1H-pyrazol- 1 -yl)propan-2-yl)carbamate Tert-butyl (S)-(1 -(3-phenyl-1H-pyrazol- 1 -yl)propan-2-yl)carbamate 3-Phenyl-1 H-pyrazole (200 mg, 1 .39 mmol), cesium carbonate (4.52 g, 13.90 mmol) and (S)-2-((tert-butoxycarbonyl)amino)propyl methanesulfonate (704 mg, 2.78 mmol) were combined in anhydrous A/,A/-dimethylformamide (4 ml). The resulting suspension was heated to 50 °C and the progress of the reaction was monitored by TLC. Once the reaction was complete (~ 3 h) the reaction mixture was quenched by addition of water and the product was extracted with ethyl acetate three times. The organic layers were combined and washed with a saturated aqueous solution of sodium chloride. The crude material was purified by column chromatography, eluting 20% ethyl acetate/petroleum spirits to give the title compound as a colourless solid (183 mg, 44%). LRMS [M+H]+ 302.2 m/z; HRMS [M+H]+ 302.1863 m/z, found 302.1867 m/z; 1H NMR (400 MHz, CDCI3) δ 7.87 - 7.70 (m, 2H), 7.41 - 7.34 (m, 3H), 7.31 - 7.25 (m, 1 H), 6.54 (d, J= 2.3 Hz, 1 H), 5.06 (d, J= 1 .1 Hz, 1 H), 4.25 (dd, J = 13.8, 4.5 Hz, 1 H), 4.20 - 4.10 (m, 1 H), 4.04 (dt, J = 12.4, 6.0 Hz, 1 H), 1 .41 (s, 10H), 1 .12 (d, J = 6.8 Hz, 3H).

Reference： [1]Current Patent Assignee: MONASH UNIVERSITY; UNIVERSITY OF WESTERN AUSTRALIA - WO2015/172196, 2015, A1 Location in patent: Paragraph 00167

31
[ 2458-26-6 ]
(2R)-2-[(tert-butoxycarbonyl)amino]propyl methanesulfonate [ No CAS ]
tert-butyl (R)-(1-(3-phenyl-1H-pyrazol-1-yl)propan-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 3h;	Jert-butyl (H)-( 1 -(3-phenyl-1H-pyrazol- 1 -yl)propan-2-yl)carbamate Jert-butyl (H)-( 1 -(3-phenyl-1H-pyrazol- 1 -yl)propan-2-yl)carbamate 3-Phenyl-1 H-pyrazole (200 mg, 1 .39 mmol), cesium carbonate (4.52 g, 13.90 mmol) and (fi)-2-((tert-butoxycarbonyl)amino)propyl methanesulfonate (704 mg, 2.78 mmol) were combined in anhydrous A/,A/-dimethylformamide (4 ml). The resulting suspension was heated to 50 °C and the progress of the reaction was monitored by TLC. Once the reaction was complete (~ 3 h) the reaction mixture was quenched by addition of water and the product was extracted with ethyl acetate three times. The organic layers were combined and washed with a saturated aqueous solution of sodium chloride. The crude material was purified by column chromatography, eluting 20% ethyl acetate/petroleum spirits to give the title compound as a colourless solid (177 mg, 42%). LRMS [M+H]+ 302.2 m/z; HRMS [M+H]+ 302.1863 m/z found 302.1864 m/z; 1H NMR (400 MHz, CDCI3) δ 7.86 - 7.73 (m, 2H), 7.43 - 7.35 (m, 3H), 7.33 - 7.27 (m, 1 H), 6.55 (d, J= 2.3 Hz, 1 H), 5.08 (s, 1 H), 4.27 (dd, J = 13.7, 4.5 Hz, 1 H), 4.23 - 4.13 (m, 1 H), 4.05 (dd, J= 12.7, 5.8 Hz, 1 H), 1 .43 (s, 9H), 1 .14 (d, J = 6.8 Hz, 3H).

Reference： [1]Current Patent Assignee: MONASH UNIVERSITY; UNIVERSITY OF WESTERN AUSTRALIA - WO2015/172196, 2015, A1 Location in patent: Paragraph 00170

32
[ 2525-62-4 ]
[ 2458-26-6 ]
N-hexyl-3-phenylpyrazole-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With dmap In pyridine at 20℃; for 12h; Inert atmosphere;	Step 3: Preparation of 3-methoxy-N-hexyl-pyrazole-1-carboxamide (23f) and 5-methoxy-N-hexylpyrazole-1-carboxamide (24f) General procedure: 3-methoxy-1H-pyrazole 14f (0.15 g, 1.53 mmol) was dissolved in dry pyridine (15 mL) and DMAP (0.02 g, 1.15 mmol) was added, followed by hexyl isocyanate (0.33 mL, 2.3 mmol). The resulting solution was stirred under nitrogen atmosphere at rt for 12 h. The solvent was evaporated under reduced pressure and the two regioisomers 23f and 24f were obtained in a ratio of 92:8, determined by 1H NMR of the crude. The mixture was separated by silica gel column chromatography using cyclohexane/EtOAc. 23f eluted with cyclohexane/EtOAc 99.5:0.5 and 24f eluted with cyclohexane/EtOAc 90:10.

Reference： [1]Diamanti, Eleonora; Bottegoni, Giovanni; Goldoni, Luca; Realini, Natalia; Pagliuca, Chiara; Bertozzi, Fabio; Piomelli, Daniele; Pizzirani, Daniela [Synthesis, 2016, vol. 48, # 17, p. 2739 - 2756]

33
[ 5720-07-0 ]
[ 2458-26-6 ]
[ 63637-59-2 ]

Yield	Reaction Conditions	Operation in experiment
79%	With pyridine; oxygen; copper(II) acetate monohydrate; triethylamine In dichloromethane at 40℃; for 2h; Flow reactor; Green chemistry;	A) catalytic Chan-Lam in flow: General procedure: A solution was prepared from the amine (0.781 mmol) in DCM (5.5 mL) and the boronic acid(1.25 mmol) and NEt3 (0.039 g, 54 μL, 0.391 mmol) were added. A second solution was prepared with Cu(OAc)2*H2O (0.195 mmol, 0.25 equiv), NEt3 (0.039 g, 54 μL, 0.391 mmol) and pyridine (0.062 g, 63 μL, 0.781 mmol) in DCM (5.5 mL). The two solutions were introduced to independent 5 mL sample loop as shown in (Scheme 1). The dispensing HPLC pumps were each set at 0.125 mL/min to achieve a residence time of 2 h. Two reverse “tubein-tube” reactors were used in series to achieve a combined reactor volume of 30 mL which were heated at 40 °C. The reaction mixture was then passed through an Omnifit column (r =0.33 cm, h = 10.00 cm) filled with QP-DMA followed by a back pressure regulator (175 psi).The crude reaction mixture was passed through a plug of silica to remove base line residue and the solvent evaporated under reduced pressure. The resultant crude material was then purified using flash chromatography.

Reference： [1]Mallia, Carl J.; Burton, Paul M.; Smith, Alexander M. R.; Walter, Gary C.; Baxendale, Ian R. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1598 - 1607]

34
[ 2458-26-6 ]
[ 98-80-6 ]
[ 4492-01-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	With pyridine; oxygen; copper(II) acetate monohydrate; triethylamine In dichloromethane at 40℃; for 2h; Flow reactor; Green chemistry;	A) catalytic Chan-Lam in flow: General procedure: A solution was prepared from the amine (0.781 mmol) in DCM (5.5 mL) and the boronic acid(1.25 mmol) and NEt3 (0.039 g, 54 μL, 0.391 mmol) were added. A second solution was prepared with Cu(OAc)2*H2O (0.195 mmol, 0.25 equiv), NEt3 (0.039 g, 54 μL, 0.391 mmol) and pyridine (0.062 g, 63 μL, 0.781 mmol) in DCM (5.5 mL). The two solutions were introduced to independent 5 mL sample loop as shown in (Scheme 1). The dispensing HPLC pumps were each set at 0.125 mL/min to achieve a residence time of 2 h. Two reverse “tubein-tube” reactors were used in series to achieve a combined reactor volume of 30 mL which were heated at 40 °C. The reaction mixture was then passed through an Omnifit column (r =0.33 cm, h = 10.00 cm) filled with QP-DMA followed by a back pressure regulator (175 psi).The crude reaction mixture was passed through a plug of silica to remove base line residue and the solvent evaporated under reduced pressure. The resultant crude material was then purified using flash chromatography.

Reference： [1]Mallia, Carl J.; Burton, Paul M.; Smith, Alexander M. R.; Walter, Gary C.; Baxendale, Ian R. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1598 - 1607]

35
[ 2458-26-6 ]
[ 128312-11-8 ]
1-(3-(methylthio)phenyl)-3-phenyl-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With pyridine; oxygen; copper(II) acetate monohydrate; triethylamine; In dichloromethane; at 40℃; under 7500.75 Torr; for 2h;Flow reactor; Green chemistry;	General procedure: A solution was prepared from the amine (0.781 mmol) in DCM (5.5 mL) and the boronic acid(1.25 mmol) and NEt3 (0.039 g, 54 muL, 0.391 mmol) were added. A second solution was prepared with Cu(OAc)2*H2O (0.195 mmol, 0.25 equiv), NEt3 (0.039 g, 54 muL, 0.391 mmol) and pyridine (0.062 g, 63 muL, 0.781 mmol) in DCM (5.5 mL). The two solutions were introduced to independent 5 mL sample loop as shown in (Scheme 1). The dispensing HPLC pumps were each set at 0.125 mL/min to achieve a residence time of 2 h. Two reverse ?tubein-tube? reactors were used in series to achieve a combined reactor volume of 30 mL which were heated at 40 C. The reaction mixture was then passed through an Omnifit column (r =0.33 cm, h = 10.00 cm) filled with QP-DMA followed by a back pressure regulator (175 psi).The crude reaction mixture was passed through a plug of silica to remove base line residue and the solvent evaporated under reduced pressure. The resultant crude material was then purified using flash chromatography.

Reference： [1]Beilstein Journal of Organic Chemistry,2016,vol. 12,p. 1598 - 1607

36
[ 2458-26-6 ]
[ 5720-06-9 ]
1-(2-methoxyphenyl)-3-phenyl-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With pyridine; oxygen; copper(II) acetate monohydrate; triethylamine In dichloromethane at 40℃; for 2h; Flow reactor; Green chemistry;	A) catalytic Chan-Lam in flow: General procedure: A solution was prepared from the amine (0.781 mmol) in DCM (5.5 mL) and the boronic acid(1.25 mmol) and NEt3 (0.039 g, 54 μL, 0.391 mmol) were added. A second solution was prepared with Cu(OAc)2*H2O (0.195 mmol, 0.25 equiv), NEt3 (0.039 g, 54 μL, 0.391 mmol) and pyridine (0.062 g, 63 μL, 0.781 mmol) in DCM (5.5 mL). The two solutions were introduced to independent 5 mL sample loop as shown in (Scheme 1). The dispensing HPLC pumps were each set at 0.125 mL/min to achieve a residence time of 2 h. Two reverse “tubein-tube” reactors were used in series to achieve a combined reactor volume of 30 mL which were heated at 40 °C. The reaction mixture was then passed through an Omnifit column (r =0.33 cm, h = 10.00 cm) filled with QP-DMA followed by a back pressure regulator (175 psi).The crude reaction mixture was passed through a plug of silica to remove base line residue and the solvent evaporated under reduced pressure. The resultant crude material was then purified using flash chromatography.

Reference： [1]Mallia, Carl J.; Burton, Paul M.; Smith, Alexander M. R.; Walter, Gary C.; Baxendale, Ian R. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1598 - 1607]

37
[ 10365-98-7 ]
[ 2458-26-6 ]
1-(3-methoxyphenyl)-3-phenyl-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With pyridine; oxygen; copper(II) acetate monohydrate; triethylamine In dichloromethane at 40℃; for 2h; Flow reactor; Green chemistry;	A) catalytic Chan-Lam in flow: General procedure: A solution was prepared from the amine (0.781 mmol) in DCM (5.5 mL) and the boronic acid(1.25 mmol) and NEt3 (0.039 g, 54 μL, 0.391 mmol) were added. A second solution was prepared with Cu(OAc)2*H2O (0.195 mmol, 0.25 equiv), NEt3 (0.039 g, 54 μL, 0.391 mmol) and pyridine (0.062 g, 63 μL, 0.781 mmol) in DCM (5.5 mL). The two solutions were introduced to independent 5 mL sample loop as shown in (Scheme 1). The dispensing HPLC pumps were each set at 0.125 mL/min to achieve a residence time of 2 h. Two reverse “tubein-tube” reactors were used in series to achieve a combined reactor volume of 30 mL which were heated at 40 °C. The reaction mixture was then passed through an Omnifit column (r =0.33 cm, h = 10.00 cm) filled with QP-DMA followed by a back pressure regulator (175 psi).The crude reaction mixture was passed through a plug of silica to remove base line residue and the solvent evaporated under reduced pressure. The resultant crude material was then purified using flash chromatography.

Reference： [1]Mallia, Carl J.; Burton, Paul M.; Smith, Alexander M. R.; Walter, Gary C.; Baxendale, Ian R. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1598 - 1607]

38
[ 2458-26-6 ]
[ 126747-14-6 ]
4-(3-phenyl-1H-pyrazol-1-yl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine; oxygen; copper(II) acetate monohydrate; triethylamine In dichloromethane at 40℃; for 2h; Flow reactor; Green chemistry;	A) catalytic Chan-Lam in flow: General procedure: A solution was prepared from the amine (0.781 mmol) in DCM (5.5 mL) and the boronic acid(1.25 mmol) and NEt3 (0.039 g, 54 μL, 0.391 mmol) were added. A second solution was prepared with Cu(OAc)2*H2O (0.195 mmol, 0.25 equiv), NEt3 (0.039 g, 54 μL, 0.391 mmol) and pyridine (0.062 g, 63 μL, 0.781 mmol) in DCM (5.5 mL). The two solutions were introduced to independent 5 mL sample loop as shown in (Scheme 1). The dispensing HPLC pumps were each set at 0.125 mL/min to achieve a residence time of 2 h. Two reverse “tubein-tube” reactors were used in series to achieve a combined reactor volume of 30 mL which were heated at 40 °C. The reaction mixture was then passed through an Omnifit column (r =0.33 cm, h = 10.00 cm) filled with QP-DMA followed by a back pressure regulator (175 psi).The crude reaction mixture was passed through a plug of silica to remove base line residue and the solvent evaporated under reduced pressure. The resultant crude material was then purified using flash chromatography.

Reference： [1]Mallia, Carl J.; Burton, Paul M.; Smith, Alexander M. R.; Walter, Gary C.; Baxendale, Ian R. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1598 - 1607]

39
[ 2458-26-6 ]
[ 150255-96-2 ]
3-(3-phenyl-1H-pyrazol-1-yl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With pyridine; oxygen; copper(II) acetate monohydrate; triethylamine In dichloromethane at 40℃; for 2h; Flow reactor; Green chemistry;	A) catalytic Chan-Lam in flow: General procedure: A solution was prepared from the amine (0.781 mmol) in DCM (5.5 mL) and the boronic acid(1.25 mmol) and NEt3 (0.039 g, 54 μL, 0.391 mmol) were added. A second solution was prepared with Cu(OAc)2*H2O (0.195 mmol, 0.25 equiv), NEt3 (0.039 g, 54 μL, 0.391 mmol) and pyridine (0.062 g, 63 μL, 0.781 mmol) in DCM (5.5 mL). The two solutions were introduced to independent 5 mL sample loop as shown in (Scheme 1). The dispensing HPLC pumps were each set at 0.125 mL/min to achieve a residence time of 2 h. Two reverse “tubein-tube” reactors were used in series to achieve a combined reactor volume of 30 mL which were heated at 40 °C. The reaction mixture was then passed through an Omnifit column (r =0.33 cm, h = 10.00 cm) filled with QP-DMA followed by a back pressure regulator (175 psi).The crude reaction mixture was passed through a plug of silica to remove base line residue and the solvent evaporated under reduced pressure. The resultant crude material was then purified using flash chromatography.

Reference： [1]Mallia, Carl J.; Burton, Paul M.; Smith, Alexander M. R.; Walter, Gary C.; Baxendale, Ian R. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1598 - 1607]

40
[ 2458-26-6 ]
[ 138642-62-3 ]
[ 1415581-19-9 ]

Yield	Reaction Conditions	Operation in experiment
38%	With pyridine; oxygen; copper(II) acetate monohydrate; triethylamine In dichloromethane at 40℃; for 2h; Flow reactor; Green chemistry;	A) catalytic Chan-Lam in flow: General procedure: A solution was prepared from the amine (0.781 mmol) in DCM (5.5 mL) and the boronic acid(1.25 mmol) and NEt3 (0.039 g, 54 μL, 0.391 mmol) were added. A second solution was prepared with Cu(OAc)2*H2O (0.195 mmol, 0.25 equiv), NEt3 (0.039 g, 54 μL, 0.391 mmol) and pyridine (0.062 g, 63 μL, 0.781 mmol) in DCM (5.5 mL). The two solutions were introduced to independent 5 mL sample loop as shown in (Scheme 1). The dispensing HPLC pumps were each set at 0.125 mL/min to achieve a residence time of 2 h. Two reverse “tubein-tube” reactors were used in series to achieve a combined reactor volume of 30 mL which were heated at 40 °C. The reaction mixture was then passed through an Omnifit column (r =0.33 cm, h = 10.00 cm) filled with QP-DMA followed by a back pressure regulator (175 psi).The crude reaction mixture was passed through a plug of silica to remove base line residue and the solvent evaporated under reduced pressure. The resultant crude material was then purified using flash chromatography.

Reference： [1]Mallia, Carl J.; Burton, Paul M.; Smith, Alexander M. R.; Walter, Gary C.; Baxendale, Ian R. [Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1598 - 1607]

41
[ 2458-26-6 ]
[ 824-79-3 ]
4-iodo-3-phenyl-1-tosyl-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With N-iodo-succinimide In ethyl acetate at 25℃; for 12h;	General procedure for the synthesis of products 5 General procedure: Pyrazoles 4 (0.5 mmol), sodium sulfinate 2 (1.0 mmol) and NBS or NIS (1.5 mmol) were dissolved in 2 mL of EtOAc solvent. the reaction mixture was stirred at room temperature under air for 12 h. After the reaction, the resulting mixture was extracted with EtOAc. The combined organic phase was dried over anhydrous Na2SO4 and the solvent was then removed under vacuum. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate, 3:1) to afford the corresponding product.

Reference： [1]Fu, Lili; Bao, Xiaodong; Li, Shanshan; Wang, Lingtian; Liu, Zhiguo; Chen, Wanzhi; Xia, Qinqin; Liang, Guang [Tetrahedron, 2017, vol. 73, # 17, p. 2504 - 2511]

42
[ 2458-26-6 ]
[ 824-79-3 ]
[ 1092565-13-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With N-Bromosuccinimide In ethyl acetate at 25℃; for 12h;	General procedure for the synthesis of products 5 General procedure: Pyrazoles 4 (0.5 mmol), sodium sulfinate 2 (1.0 mmol) and NBS or NIS (1.5 mmol) were dissolved in 2 mL of EtOAc solvent. the reaction mixture was stirred at room temperature under air for 12 h. After the reaction, the resulting mixture was extracted with EtOAc. The combined organic phase was dried over anhydrous Na2SO4 and the solvent was then removed under vacuum. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate, 3:1) to afford the corresponding product.

Reference： [1]Fu, Lili; Bao, Xiaodong; Li, Shanshan; Wang, Lingtian; Liu, Zhiguo; Chen, Wanzhi; Xia, Qinqin; Liang, Guang [Tetrahedron, 2017, vol. 73, # 17, p. 2504 - 2511]

43
[ 2458-26-6 ]
[ 1452-94-4 ]
[ 1037828-53-7 ]

Yield	Reaction Conditions	Operation in experiment
85.1%	With 18-crown-6 ether; potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 130℃; Inert atmosphere;
28.5%	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 130℃; for 16h;	27 To a solution of ethyl2-chloronicotinate (2 g, 10.78 mmol) and 3-phenyl-1H-pyrazo1e (2.33 g, 16.16 mmol) in DMF (30 mL) was added K2C03 (4.47 g, 32.33 mmol)and Kl (1.79 g, 10.78 mmol). The mixture was stirred at 130 oc for 16h. The reaction wasfiltered, the filtrate was added I-hO (100 mL), extracted with EA (30 mL x2), the organicphase was washed with brine ( l 00 mL ), filtered, and concentrated. The residue was purifiedby flash silica gel chromatography (ISCO; 40 g SepaFlash Silica Flash Column, Eluent of15(% Ethyl acetate/Petroleum ethergradient 40 mUmin). Compound 113A (1 g, yield:28.5%) was obtained as a white solid. 1H NMR (400MHz, CDCh) 8 8.49 (dd, J = 1.7, 4.6Hz, lH), 8.42 (d, J"' 2.4 Hz, 1H), 7.94 (dd, J '" 1.7, 7.6 Hz, lH), 7.89- 7.78 (m, 2H), 7.40 (t,J "' 7.3 Hz, 2H), 7.33 (br d, J '" 7.3 Hz, H-I), 7.29 - 7.23 (m, HI), 6.79 (d, J "' 2.7 Hz, HI),4.45- 4.25 (m, 2H), 1.14 (t, J = 7.2 Hz, 3H). MS (ESl) m/z (M+Ht294.1.

Reference： [1]Kling, Andreas; Jantos, Katja; Mack, Helmut; Hornberger, Wilfried; Drescher, Karla; Nimmrich, Volker; Relo, Ana; Wicke, Karsten; Hutchins, Charles W.; Lao, Yanbin; Marsh, Kennan; Moeller, Achim [Journal of Medicinal Chemistry, 2017, vol. 60, # 16, p. 7123 - 7138]
[2]Current Patent Assignee: BLADE THERAPEUTICS INC; BLADE THERAPERTICS - WO2019/190885, 2019, A1 Location in patent: Paragraph 0523

44
[ 942289-64-7 ]
[ 2458-26-6 ]
methyl 1-methyl-2-(5-phenyl-1H-pyrazol-1-yl)-1H-1,3-benzodiazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 3h; Sealed tube;	3 Methyl 1-methyl-2-(5-phenyl-1H-pyrazol-1-yl)-1H-1,3-benzodiazole-5- carboxylate (EV-AQ1926-001)- Step 3 Methyl 1-methyl-2-(5-phenyl-1H-pyrazol-1-yl)-1H-1,3-benzodiazole-5- carboxylate (EV-AQ1926-001)- Step 3 To a solution of methyl 2-bromo-1-methyl-1H-1,3-benzodiazole-5-carboxylate (EV- AP4096-001, 57 mg, 0.20 mmol) in DMF (1 ml) in a pressure tube was added potassium carbonate (56.2 mg, 0.41 mmol) followed by 3-phenyl-1H-pyrazole (CAS 2458-26-6, 44.0 mg, 0.31 mmol). The vessel was sealed and the reaction mixture was stirred at 120°C for 3h. The mixture was allowed to cool to room temperature and partitioned between ethyl acetate (5 ml) and water (5 ml). The aqueous layer was extracted with ethyl acetate (5 ml) then the combined organic extracts were evaporated to dryness and azeotroped with heptane. The crude material was purified by flash column chromatography (0- 60% ethyl acetate/heptane) to obtain 24 mg (35%) of methyl 1-methyl-2-(5-phenyl-1H-pyrazol-1-yl)-1H-1,3-benzodiazole-5-carboxylate (EV-AQ1926-001) as a white solid. LCMS (method D): retention time 1.48min, M/z = 333 (M + 1).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2017/147102, 2017, A1 Location in patent: Paragraph 00260-00261

45
[ 2458-26-6 ]
[ 2926-30-9 ]
[ 362601-71-6 ]

Yield	Reaction Conditions	Operation in experiment
28%	With H₂O₈S₂*2H₃N; [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine-N¹,N¹]bis-{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C}iridium(III) hexafluorophosphate In dimethyl sulfoxide at 40℃; for 0.5h; Flow reactor; UV-irradiation;	Trifluoromethylation; General Procedure: General procedure: In an oven-dried vial equipped with a magnetic stirrer and a PTFE septum, [Ir{dF(CF3)ppy}2](dtbpy)]PF6 (5.6 mg, 1 mol%) was added to a mixture of the substrate (0.5 mmol, 1 equiv), CF3SO2Na (1.5 mmol, 3 equiv), and (NH4)2S2O8 (0.5 mmol, 1 equiv) in DMSO (5 mL). The solution was pumped into the Vapourtec photoreactor (fluoropolymer tube, 1.3 mm i.d., 10 mL) and the liquid flowrate was set at 0.33 mL/min (30 min residence time). The reactor was irradiated with 54 blue LEDs (450 nm, total power 24 W). The reaction mixture collected from the outlet was diluted with H2O and extracted with Et2O (3×). The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo. The crude was then pre-adsorbed onto silica, dried in vacuo, and purified by flash chromatography to yield the trifluoromethylated product.

Reference： [1]Abdiaj, Irini; Bottecchia, Cecilia; Alcazar, Jesus; Noël, Timothy [Synthesis, 2017, vol. 49, # 22, p. 4978 - 4985]

46
[ 4470-83-1 ]
[ 2458-26-6 ]
C₁₈H₁₂ClN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: All the ligands and the corresponding complexes were synthesized in the similar manner; a typical synthesis of complex 3a is described as follows: in a 100mL flask, pyrazole (0.69g 10.09mmol) was dissolved in 50mL of DMF, and NaH (0.29g, 12.16mmol) was added to the solution, the reaction mixture was stirred for 30min. 2,8-Dichloroquinoline (2.0g, 10.09mmol) was then slowly added to the flask, after the reaction mixture was refluxed for 48h under a nitrogen atmosphere, the reaction was terminated with ice water after cooling to room temperature, and a white suspension was formed. The precipitate was filtered and recrystallized from ethanol, and dried under vacuum at 30C to give the desired product 1a as a white solid.

Reference： [1]Inorganica Chimica Acta,2018,vol. 474,p. 37 - 43

47
[ 2458-26-6 ]
C₉H₇BrN₂ [ No CAS ]
[ 13808-65-6 ]

Reference： [1]Advanced Synthesis and Catalysis,2018,vol. 360,p. 626 - 630

48
[ 2458-26-6 ]
[ 3356-89-6 ]
3-phenyl-5-(3-phenyl-1H-pyrazol-1-yl)isoxazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2018,vol. 83,p. 3177 - 3187

49
[ 2458-26-6 ]
[ 3356-89-6 ]
(3-phenyl-1H-pyrazol-1-yl)(3-phenyl-2H-azirin-2-yl)methanone [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2018,vol. 83,p. 3177 - 3187

50
[ 2458-26-6 ]
[ 3356-94-3 ]
C₁₆H₁₅N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40.8%	With potassium carbonate; In N,N-dimethyl-formamide; at 80.0℃; for 12.0h;	[1097] to a mixture of <strong>[3356-94-3]ethyl 5-chloro-3-methylisoxazole-4-carboxylate</strong> (400 mg, 2.1 mmol) and 3-phenyl-1H-pyrazole (365 mg, 2.5 mmol) in DMF(3 ml) was added K2CO3 (1.2 g,8.4 mmol) in one portion. Then the mixture was stirred at 80 C for 12 hours. Then H2O (9 ml) was added into the mixture, and the aqueous phase was extracted with EtOAc (15 ml x 3), and the combined organic layer was concentrated to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether: ethyl acetate = 300: 1 to 30: 1). Compound 211a (256 mg, yield: 40.8%, pale yellow solid): 1H NMR (400mhz, CDCl3) delta 8.62 (d, = 2.6 hz, 1h), 7.93 (d, j = 6.8 hz, 2h), 7.49 - 7.37 (m, 3h), 6.86 (d, j = 2.6 hz, 1h), 4.37 (q, j = 1.1 hz, 2h), 2.53 (s, 3h), 1.40 - 1.34 (m, 2h), 1.41 - 1.33 (m, 1h).

Reference： [1]Patent: WO2018/64119,2018,A1 .Location in patent: Paragraph 1097

51
[ 10242-08-7 ]
[ 2458-26-6 ]
C₁₉H₁₄N₂O₃ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 6242 - 6246
Angew. Chem.,2018,vol. 130,p. 6350 - 6354,5

52
[ 10242-11-2 ]
[ 2458-26-6 ]
C₁₈H₁₁BrN₂O₂ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 6242 - 6246
Angew. Chem.,2018,vol. 130,p. 6350 - 6354,5

53
[ 2458-26-6 ]
[ 98-89-5 ]
C₁₅H₁₈N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N′,N′-tetramethyl-N″-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate In 1,4-dioxane at 20℃; for 1h; Inert atmosphere; Irradiation; regioselective reaction;	Procedure for decarboxylative sp3 C-N couplings General procedure: To a 20 ml or 40 ml viale quipped with a stir bar was added photocatalyst, nitrogen nucleophile, iodomesitylene dicarboxylate, copper salt, and ligand. Dioxane was added followed by addition of the base. The solution was sonicated for 1-3 min until it became homogeneous. Next, the solution was degassed by sparging with nitrogen for 5-10 min before sealing with Parafilm. The reaction was stirred and irradiated using two 34-W blue LED lamps (3 cm away, with cooling fan to keep the reaction at room temperature) for 1 h. The reaction mixture was removed from the light, cooled to ambient temperature, diluted with water (15 ml) and ethyl acetate (25 ml), and the aqueous layer was extracted with ethyl acetate (3 × 25 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel to afford the desired decarboxylative C-N coupling product. For aniline substrates, a solution of these nitrogen nucleophiles in dioxane was used; additionally, if the iodomesitylene dicarboxylate is a liquid, its solution in dioxane was used.

Reference： [1]Liang, Yufan; Zhang, Xiaheng; MacMillan, David W. C. [Nature, 2018, vol. 559, # 7712, p. 83 - 88]

54
[ 65094-22-6 ]
[ 2458-26-6 ]
1-(difluoromethyl)-3-phenyl-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium fluoride In acetonitrile at 20℃; for 12h; Schlenk technique; Inert atmosphere; Green chemistry;	General Procedure For the N-Difluoromethylation of Imidazoles and Pyrazoles. General procedure: To a 25 mL of Schlenk tube equipped with a Teflon septum were added Imidazoles/Pyrazoles (0.4 mmol, 1.0 equiv) and KF (46.4 mg, 2.0 equiv) under Ar, followed by MeCN (3 mL) with stirring. 2 (0.40 mmol, 1.0 equiv) were added subsequently. After stirring for 12 h, the reaction mixture was concentrated. The residue was purified with silica gel chromatography to provide pure product.

Reference： [1]Mao, Ting; Zhao, Liang; Huang, Yang; Lou, Yue-Guang; Yao, Qiuli; Li, Xiao-Fei; He, Chun-Yang [Tetrahedron Letters, 2018, vol. 59, # 28, p. 2752 - 2754]

55
[ 493-05-0 ]
[ 2458-26-6 ]
C₁₈H₁₆N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With [bis(acetoxy)iodo]benzene In 1,2-dichloro-ethane at 20 - 80℃; for 6h; Schlenk technique;	1-(3,4-Dihydro-1H-isochromen-1-yl)-1H-benzimidazole(3aa; Ref. 6); Typical Procedure General procedure: PhI(OAc)2 (0.5 mmol) was added to a mixture of 1H-benzimidazole(1a; 0.5 mmol), isochroman (2a; 2.0 mmol), and DCE (2.0mL) in a Schlenk tube at r.t. The mixture was stirred at 80 °C for6 h then cooled. H2O (10 mL) was added, and the mixture wasextracted with CH2Cl2 (3 × 10 mL). The combined organic layerwas dried (Na2SO4) and concentrated under reduced pressure.The residues were purified by flash column chromatography(silica gel, hexane-EtOAc) to give a colorless oil; yield: 115 mg(92%).

Reference： [1]Sun, Bin; Yan, Zhiyang; Jin, Can; Su, Weike [Synlett, 2018, vol. 29, # 18, p. 2432 - 2436]

56
[ 2458-26-6 ]
2-chloro-N-(1-cyclohexyl-3-methyl-1H-pyrazol-5-yl)acetamide [ No CAS ]
N-(1-cyclohexyl-3-methyl-1H-pyrazol-5-yl)-2-(3-phenyl-1H-pyrazol-1-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium ethanolate In ethanol at 90℃; for 2h; Microwave irradiation;	N-(1-cyclohexyl-3-methyl-1H-pyrazol-5-yl)-2-(5-(pyridin-3-yl)-2H-tetrazol-2-yl)acetamide (16a). General procedure: In a 10 mL Microwave vial, 2-chloro-N-(1-cyclohexyl-3-methyl-1H-pyrazol-5-yl)acetamide (50.0 mg, 0.19 mmol), 3-(2H-tetrazol-5-yl)pyridine (28.2 mg, 0.19 mmol) and NaOEt 15.6 mg, 0.23 mmol) in ethanol (1.5 mL) was subjected to microwave irradiation at 90 C for 2 h. Crude was partitioned between brine (20 mL) and ethyl acetate (25 mL*2), combined organic layer was dried over sodium sulphate, concentrated and purified by Preparative HPLC (0-100% ACN in water). (24 mg, 76%)

Reference： [1]Sharma, Swagat; Kozek, Krystian A.; Abney, Kristopher K.; Kumar, Sushil; Gautam, Nagsen; Alnouti, Yazen; David Weaver; Hopkins, Corey R. [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 6, p. 791 - 796]

57
[ 154258-82-9 ]
[ 2458-26-6 ]

Reference： [1]Organic Letters,2019,vol. 21,p. 2482 - 2487

58
[ 149739-32-2 ]
[ 2458-26-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With 2-methyl-propan-1-ol; methanesulfonato(2-dicyclohexylphosphino -2’,6’-di-i-propoxy-1,1‘-biphenyl)(2’-amino-1,1’-biphenyl-2-yl)palladium(II); sodium tert-pentoxide In toluene at 80℃; for 18h; Sealed tube; Inert atmosphere;
92%	With (2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1‘-biphenyl)[2-(2’-methylamino-1,1’-biphenyl)]palladium(II) methanesulfonate; sodium tert-pentoxide; isopropyl alcohol In toluene at 80℃; Inert atmosphere;

Reference： [1]Gair, Joseph J.; Grey, Ronald L.; Giroux, Simon; Brodney, Michael A. [Organic Letters, 2019, vol. 21, # 7, p. 2482 - 2487]
[2]Brodney, Michael A.; Gair, Joseph J.; Giroux, Simon; Grey, Ronald L. [Organic Syntheses, 2021, vol. 98, p. 131 - 146]

59
[ 66107-34-4 ]
[ 2458-26-6 ]
3-phenyl-1-(2-methylphenyl)-1H-pyrazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 6508 - 6515

60
[ 86-75-9 ]
[ 2458-26-6 ]
4-(3-phenyl-1H-pyrazol-1-yl)quinolin-8-yl benzoate. [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With dipotassium peroxodisulfate; tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; silver(I) triflimide In acetonitrile at 20℃; for 12h; Schlenk technique; Inert atmosphere; Irradiation; regioselective reaction;	(a) Procedure for the synthesis of 3: General procedure: A 25mL Schlenk tube was equipped with a magnetic stir bar and charged with 8- hydroxylquinoline ester 1(24.9 mg, 0.1 mmol), pyrazole 2 (16.8mg, 0.25 mmol, 2.5 equiv), [Ru(bpy)3](PF6)2 (2.0mg, 0.003 mmol, 3 mol %), AgNTf2 (3.9 mg, 0.01 mmol, 10 mol%), K2S2O8 (54 mg, 0.2 mmol, 2 equiv), and CH3CN (1.5 mL). The resulting mixture was stirred by the blue LED irradiation under argon at room temperature for 12 h. Upon completion, CH2Cl2 (20 mL) was added tothe reaction system, and the resulting mixture was filtered through a pad of Celite. The organic layer was dried over anhydrous Na2SO4 and filtered. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel (100200 meshes) using hexane/EtOAc as an eluent (5:1, V/V) to afford the pure product 3.

Reference： [1]Ma, Yueyue; Shi, Yaqi; Yang, Fan; Wu, Yusheng; Wu, Yangjie [Tetrahedron, 2019, vol. 75, # 29, p. 3904 - 3910]

61
[ 4187-87-5 ]
[ 2458-26-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With C₂₄H₂₀N₂O₄Ru; hydrazine hydrate In toluene at 150℃; Inert atmosphere; Microwave irradiation;	General catalytic procedure General procedure: Catalyst 1 (0.02 mmol) was dissolved in toluene (2 mL) and the propargyl alcohol (1 mmol) and hydrazine hydrate (2 mmol) or phenylhydrazine (1 mmol) were subsequently added. The mixture was heated to 150 °C for 15-30 minutes using microwave irradiation. Evaporation of the solvent and flash chromatography on silica (gradient: pentane/ethyl acetate) furnished the purified products as colorless or yellow oils or foams.

Reference： [1]Kaufmann, Julia; Jäckel, Elisabeth; Haak, Edgar [Arkivoc, 2019, vol. 2019, # 4, p. 91 - 101]

62
[ 1570134-59-6 ]
[ 2458-26-6 ]
N-(2-(4,5-dihydrooxazol-2-yl)phenyl)-2-methyl-6-(3-phenyl-1H-pyrazol-1-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium acetate; copper(I) bromide In dimethyl sulfoxide at 85℃; for 12h; Schlenk technique; Sealed tube;	41 Example 41 Aromatic substrate 1b (0.1mmol), 3-phenylpyrazole 2m (0.15mmol), cuprous bromide (0.1mmol), potassium acetate (0.2mmol), DMSO (1.0mL) were added to the 15mL Schlenk tube, then directly sealed tube at 85 ° C for 12h. After the reaction was completed, the mixture was cooled to room temperature, and a small amount of ethyl acetate and ammonia were added to quench the reaction. The ethyl acetate was repeatedly extracted. The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered under reduced pressure, and the solvent was evaporated under reduced pressure. The crude product was separated and purified by a preparative plate (DCM: MeOH = 35: 1) to obtain 3bm as a white solid, 29.4 mg, with a yield of 70%.
70%	With copper diacetate; sodium carbonate In dimethyl sulfoxide at 90℃; for 6.5h; Sealed tube; regioselective reaction;

Reference： [1]Current Patent Assignee: SHANGHAI RAAS BLOOD PRODUCTS COMPANY LIMITED - CN110386929, 2019, A Location in patent: Paragraph 0108; 0109
[2]Yu, Jin-Feng; Li, Jian-Jun; Wang, Peng; Yu, Jin-Quan [Angewandte Chemie - International Edition, 2019, vol. 58, # 50, p. 18141 - 18145][Angew. Chem., 2019, vol. 131, p. 18309 - 18313,5]

63
[ 84766-91-6 ]
[ 2458-26-6 ]
tert-butyl 2-(5-phenyl-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Chemical Communications,2019,vol. 55,p. 15089 - 15092

64
[ 1504-58-1 ]
[ 2458-26-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With bismuth(lll) trifluoromethanesulfonate; N-Bromosuccinimide; hydrazine hydrate In 1,4-dioxane at 101℃; for 5h; Sealed tube;	1 The preparation process is: Add a propargyl alcohol derivative, a halogen source and an acid to a sealed tube, and carry out the reaction under heating at 101 °C. After the propargyl alcohol derivative is completely disappeared by TLC, hydrazine is added. After 5 hours of reaction, it is quenched with saturated saline, the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated to obtain a pyrazole derivative. The purity of the product was improved by column chromatography, and the calculated yield was 91.0%. Of which propargyl alcohol, halogen source, hydrazine, solvent and acid were added as 3-phenylprop-2-yn-1-ol (2mmol), NBS (2mmol), hydrazine hydrate (2.1mmol), dioxane (10 mL) and bismuth triflate (0.1 mmol).

Reference： [1]Current Patent Assignee: SHANGHAI INSTITUE OF TECHNOLOGY - CN110483400, 2019, A Location in patent: Paragraph 0051-005

65
[ 5468-77-9 ]
[ 2458-26-6 ]
(3-phenyl-pyrazol-1-yl)-acetic acid dimethylamide [ No CAS ]