Name: 624-75-9|2-Iodoacetonitrile|96%
Brand: Ambeed
SKU: A911763
Price: 9.0 USD
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1
[ 624-75-9 ]
[ 698-70-4 ]
N-(4-iodo-phenyl)-N-methyl-glycine nitrile [ No CAS ]
[ 19095-34-2 ]

Reference： [1]Chemische Berichte,1908,vol. 41,p. 2117
Chemische Berichte,1909,vol. 42,p. 2056

2
[ 39998-25-9 ]
[ 624-75-9 ]
[ 89058-79-7 ]

Reference： [1]Tetrahedron,1983,vol. 39,p. 3055 - 3058

3
[ 624-75-9 ]
[ 100-52-7 ]
[ 1885-38-7 ]
[ 24840-05-9 ]

Reference： [1]Synthetic Communications,1989,vol. 19,p. 83 - 90

4
[ 624-75-9 ]
[ 530-78-9 ]
[ 21858-38-8 ]

Reference： [1]Analytical Chemistry,1995,vol. 67,p. 1853 - 1859

5
[ 624-75-9 ]
[ 14097-39-3 ]
2-cyanomethyl-6-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinolinium iodide [ No CAS ]

Reference： [1]Tetrahedron,1995,vol. 51,p. 10189 - 10204

6
[ 624-75-9 ]
[ 4394-00-7 ]
2-(3-Trifluoromethyl-phenylamino)-nicotinic acid cyanomethyl ester [ No CAS ]

Reference： [1]Analytical Chemistry,1995,vol. 67,p. 1853 - 1859

7
[ 624-75-9 ]
[ 13710-19-5 ]
2-(3-Chloro-2-methyl-phenylamino)-benzoic acid cyanomethyl ester [ No CAS ]

Reference： [1]Analytical Chemistry,1995,vol. 67,p. 1853 - 1859

8
[ 13697-89-7 ]
[ 75-05-8 ]
[ 624-75-9 ]
[ 372-18-9 ]
[ 2265-93-2 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1997,vol. 70,p. 1875 - 1878

9
[ 624-75-9 ]
[ 197902-43-5 ]
[ 197902-44-6 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 10877 - 10887

10
[ 624-75-9 ]
[ 197902-50-4 ]
[ 197902-51-5 ]

Reference： [1]Journal of the American Chemical Society,1997,vol. 119,p. 10877 - 10887

11
[ 624-75-9 ]
[ 594-09-2 ]
(cyanomethyl)trimethyl-phosphonium iodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In tetrahydrofuran; toluene; at 0 - 20℃; for 51h;Inert atmosphere;	A. A solution of trimethylphosphine in toluene (1 M, 60 mL, 60 mmol) at 0 C under nitrogen was diluted with toluene(30 mL) and tetrahydrofuran (30 mL). <strong>[624-75-9]Iodoacetonitrile</strong> (4.2 mL, 9.69 g, 58 mmol) was then added dropwise whilestirring vigorously, whereby a colorless solid precipitated. When the addition was finished, the ice-bath was removedand stirring was continued at ambient temperature for 51 h. The mixture was filtered, and the solid was washed withtoluene and dried under reduced pressure. Recrystallization from acetonitrile (37.5 mL) to give the compound ascolorless crystals (9.89 g, yield: 70%).
68.3%	In tetrahydrofuran; toluene; at 20℃;Cooling with ice;	Cyanomethyl)trimethylphosphonium iodide was prepared according to the general method described in Zaragoza, F., et al., J. Org. Chem.2001, 66, 2518-2521. In a 1 L round bottom flask, trimethylphosphine in toluene (100 mL, 100 mmol) was diluted with THF (50.0 mL) and toluene (50.0 mL), and cooled on an ice bath. The reaction mixture was stirred vigorously while <strong>[624-75-9]iodoacetonitrile</strong> (7 mL, 16.7 g, 68.3 mmol) was added dropwise to produce a tan precipitate. The cooling bath was removed and the reaction mixture was stirred overnight at room temperature. The flask was placed in a sonicator to break up any clumped solids. The reaction mixture was stirred an additional 4 hours. The solids were collected by filtration and dried under vacuum to give (1380) (cyanomethyl)trimethylphosphonium iodide (16.6 g, 68.3 mmol, 68.3 % yield). 1H NMR (400 MHz, DMSO-d6) 4.03 (d, J=16.4 Hz, 2H), 2.05 (d, J=15.4 Hz, 9H).
66%	In toluene; at 0 - 20℃; for 40h;	Cyanomethyl-trimethyl-phosphonium iodide (TJA01110); C5H11INP MW 243.03 Trimethylphosphine in THF (1M, 20.0 mL, 20.0 mmol) at 0 C under N2 (g) was diluted with anhydrous toluene (40 mL). <strong>[624-75-9]Iodoacetonitrile</strong> (1.40 mL, 19.4 mmol) was added dropwise with vigorous stirring forming a white ppt. The mixture was allowed to warm to r. t. and left to stir for 40 h. The mixture was filtered and washed with toluene to give a white solid which was dried under vacuum. Recrystallisation (acetonitrile) provided the title compound as a white crystalline solid (3.23 g, 66 %), ¹H NMR (300 MHz, DMSO-d6) No. 2.01-2.06 (9H, d, J= 15.3 Hz, P (CH3)3), (2H, d, J= 16.4 Hz, PCH2CN); 3¹p NMR (121.5 MHz, DMSO-d6) No. 32.9.

66%	In toluene; at 0 - 20℃; for 40h;	Cyanomethyl-trimethyl-phosphonium iodide (TJA01110) C5H11INP MW 243.03. Trimethylphosphine in THF (IM, 20.0 mL, 20.0 mmol) at 0 0C under N2 (g) was diluted with anhydrous toluene (40 mL). <strong>[624-75-9]Iodoacetonitrile</strong> (1.40 mL, 19.4 mmol) was added dropwise with vigorous stirring forming a white ppt. The mixture was allowed to warm to r.t. and left to stir for 40 h. The mixture was filtered and washed with toluene to give a white solid which was dried under vacuum. Recrystallisation (acetonitrile) provided the title compound as a white crystalline solid (3.23 g, 66 %), 1H NMR (300 MHz, DMSO-J6) delta 2.01-2.06 (9H, d, J= 15.3 Hz, P(CHs)3), 4.01-4.07 (2H, d, J= 16.4 Hz, PCH2CN);31P NMR (121.5 MHz, DMSO-J6) delta 32.9.
		The synthesis of (cyanomethyl)trimethylphosphonium iodide is carried out in very much the same way as the procedure described in the literature [J. Org. Chem. 2001, 66, 2518-2521] from trimethylphosphine and <strong>[624-75-9]iodoacetonitrile</strong>. 2.42 g of (cyanomethyl)trimethylphosphonium iodide is added to a solution of 1 g of alcohol 8 in 18 ml of propionitrile, and then 2.1 ml of diisopropyl ethylamine is added in drops. The reaction mixture is stirred for 14 hours at 97 C. After cooling to room temperature, the batch is mixed with 10 ml of water and 1 ml of concentrated hydrochloric acid. The phase separation is carried out between ethyl acetate/water. The organic phase is washed with water and saturated sodium chloride solution, dried on magnesium sulfate and concentrated by evaporation. Column-chromatographic purification (cyclohexane/ethyl acetate) yields 480 mg of cyanide 11b as a colorless foam (GC-MS: m/z theor.: 535, pract.: 535).

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 6055 - 6069
[2]Journal of Organic Chemistry,2001,vol. 66,p. 2518 - 2521
[3]Patent: EP2316827,2016,B1 .Location in patent: Paragraph 0121
[4]Patent: WO2020/6018,2020,A1 .Location in patent: Page/Page column 344
[5]Patent: WO2005/118560,2005,A1 .Location in patent: Page/Page column 99
[6]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 131-132
[7]Patent: US2005/65135,2005,A1 .Location in patent: Page/Page column 18

12
[ 624-75-9 ]
[ 349609-18-3 ]
[ 349609-09-2 ]

Reference： [1]Angewandte Chemie - International Edition,2001,vol. 40,p. 1463 - 1465
[2]Journal of the American Chemical Society,2002,vol. 124,p. 2951 - 2956

13
[ 631908-27-5 ]
[ 624-75-9 ]
[ 631908-38-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; In acetonitrile; at 0 - 20℃; for 16h;	A 50 mL round-bottomed flask equipped with a magnetic stirrer was charged with 1-(2-fluorobenzenesulfonyl)-4-hydroxy-1H-indole (0.600 g, 0.002 mol), 25 mL of anhydrous acetonitrile and potassium carbonate (1.104 g, 0.008 mol). The reaction mixture was cooled to 0 C. and <strong>[624-75-9]iodoacetonitrile</strong> (0.500 g, 0.003 mol) was added dropwise over five minutes. The reaction mixture was allowed to warm to ambient temperature and stirred for eighteen hours. The mixture was taken in ether (200 mL), washed with water (2×30 mL) and brine (1×30 mL), dried over MgSO4 and concentrated in vacuo. The resulting oily brown residue was purified by flash chromatography (8:2 ethyl acetate/hexanes) to give [1-(2-fluoro-benzenesulfonyl)-1H-indol-4-yloxy]acetonitrile as a crystalline solid (0.507 g, 77%). 1H NMR (300 MHz, CDCl3) delta: 4.87 (s, 2H), 6.76 (d, 1H. J=13.18), 6.77 (d, 1H, J=1.51), 7.11 (dt, 1H, J=8.29, J=1.13), 7.23 (t, 1H, J=8.29), 7.29 (dt, 1H, J=7.73, J=1.13), 7.58 (m, 4H), 8.03 (m, 1H).

Reference： [1]Patent: US2003/229069,2003,A1 .Location in patent: Page 16

14
C₂₃H₁₈N₈O [ No CAS ]
[ 624-75-9 ]
C₂₅H₁₉N₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With potassium carbonate; In acetonitrile; at 20℃; for 408h;	Compound 6 (prepared according to B2. b) (30 mg) was dissolved in 20 ml of MECN, and iodo acetonitrile (1.0 eq. ) and K2CO3 (3 eq, 29 mg) were added. Stirring for 17 days at 20C. The MECN was evaporated and the residue was purified by preparative TLC using CHCL2/MEOH (9/1) as the eluent. Yield: compound 60 (52 %).

Reference： [1]Patent: WO2005/28479,2005,A2 .Location in patent: Page/Page column 72

15
[ 624-75-9 ]
[ 465529-53-7 ]
[ 847201-18-7 ]

Yield	Reaction Conditions	Operation in experiment
38%	With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 65℃; for 0.5h;	A mixture of [4- (4-HYDROXYPHENYL) butyl] carbamic acid tert-butyl ester 31 (0.365 g, 1.37 mmol) and Cs2CO3 (0.672 g, 2.06 mmol) in anhydrous DMF (8 mL) was heated at 65 C for 30 min. IODOACETONITRILE (0.276 g, 1.651 mmol) was then added to the mixture in one portion. The mixture was stirred at 65 C overnight, and then cooled to room temperature. The precipitated solid was filtered, and the filtrate was partitioned between water and dichloromethane (each 50 mL). The organic layer was separated, washed with brine (3 x 50 mL), dried over anhydrous NA2S04 and concentrated under vacuum. The residue was chromatographed on silica gel, eluting with a mixture of diethyl ether/dichloromethane (6: 94, v/v), to afford the desired product 40 (0.109 g, 38% yield) as a colorless viscous OIL. 1H NMR (300 MHz, CDC13) : 8 1.43 (s, 9H), 1.57 (M, 4H), 2.60 (t, 2H), 3.15 (M, 2H), 4.49 (br, 1H), 4.75 (s, 2H), 6.91 (d, 2H), 7.13 (d, 2H).

Reference： [1]Patent: WO2005/18644,2005,A1 .Location in patent: Page 46; 68

16
[ 865305-08-4 ]
[ 624-75-9 ]
[ 865305-10-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 60℃; for 0.5h;	To a mixture of 5-bromo-2-isopropyl-4-methoxy-phenol from step 4 (0.831 g, 3.4 mmol) and K2CO3 (0.562 g, 4.1 mmol) in 17 mL dimethyl formamide (DMF) was added <strong>[624-75-9]iodoacetonitrile</strong> (0.594 g, 3.6 mmol). The mixture was warmed to 60 C. for 30 minutes and then allowed to cool to room temperature. After cooling to room temperature the mixture was taken up in 50 mL of H2O and extracted with 1:1 toluene/ethyl acetate, washed with H2O and then with brine. The combined organic layers were dried over Na2SO4, filtered and conectrated in vacuo to give a crude solid. Purification via flash chromatography (1:1 hexane/CH2Cl2) afforded (5-bromo-2-isopropyl-4-methoxy-phenoxy)-acetonitrile (0.611 g, 63%) as a while solid.
63%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 0.5h;	To a mixture of 5-bromo-2-isopropyl-4-methoxy-phenol from step 4 (0.831 g, 3.4 mmol) and K2CO3 (0.562 g, 4.1 mmol) in 17 mL dimethyl formamide (DMF) was added <strong>[624-75-9]iodoacetonitrile</strong> (0.594 g, 3.6 mmol). The mixture was warmed to 60 C. for 30 minutes and then allowed to cool to room temperature. After cooling to room temperature the mixture was taken up in 50 mL of H2O and extracted with 1:1 toluene/ethyl acetate, washed with H2O and then with brine. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a crude solid. Purification via flash chromatography (1:1 hexane/CH2Cl2) afforded (5-bromo-2-isopropyl-4-methoxy-phenoxy)-acetonitrile (0.611 g, 63%) as a while solid.
63%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 0.5h;	To a mixture of 5-bromo-2-isopropyl-4-methoxy- phenol from step 4(0.831 g, 34 mmol) and K2C03 (0.562 g, 4.1 mmol) in 17 mE dimethyl formamide (DMF) was added <strong>[624-75-9]iodoacetonitrile</strong> (0.594 g, 3.6 mmol). The mixture was warmed to 60 C. for 30 minutes and then allowed to cool to room temperature. After cooling to room temperature the mixture was taken up in SOmE of H20 and extracted with 1:1 toluene/ethyl acetate, washed with H20 and then with brine. The combined organic layers were dried over Na2504, filtered and concentrated in vacuo to give a crude solid. Purification via flash chromatography (1:1 hexane/CH2C12) afforded (5-bromo-2-isopropyl-4-methoxy-phenoxy)-aceto- nitrile (0.611 g, 63%) as a while solid.

63%

With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 0.5h;

j181j To a mixture of 5-bromo-2-isopropyl-4-methoxy-phenol from step 4 (0.831 g, 3.4 mmol) and K2C03 (0.562 g, 4.1 mmol) in 17 mL dimethyl formamide (DMF) was added [624-75-9]iodoacetonitrile (0.594 g, 3.6 mmol). The mixture was warmed to 60 C for 30 minutes and then allowed to cool to room temperature. After cooling to room temperature the mixture was taken up in 50 mL of H20 and extracted with 1:1 toluene/ethyl acetate, washed with H20 and then with brine. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a crude solid. Purification via flash chromatography (1:1 hexane/CH2C12) afforded (5-bromo-2-isopropyl-4-methoxy-phenoxy)-acetonitrile (0.611 g, 63%) as a while solid.

Reference： [1]Patent: US2005/209260,2005,A1 .Location in patent: Page/Page column 81
[2]Patent: US2007/49609,2007,A1 .Location in patent: Page/Page column 78
[3]Patent: US2015/57299,2015,A1 .Location in patent: Paragraph 0150
[4]Patent: WO2016/4358,2016,A1 .Location in patent: Paragraph 176; 181
[5]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1628 - 1631

17
[ 531506-28-2 ]
[ 624-75-9 ]
[ 531506-29-3 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; ethyl acetate;	e) To a solution of 7-benzyloxymethyl-8-(4-hydroxyphenyl)-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione (1 g, 2.2 mmol) in tetrahydrofuran (20 ml) was added potassium t-butoxide (0.28 g, 2.4 mmol), and the mixture stirred for 30 minutes at room temperature. <strong>[624-75-9]Iodoacetonitrile</strong> (0.38 g, 2.23 mmol) was then added, and the mixture stirred for 16 hours at room temperature. The solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate and passed through a silica gel plug, to provide 7-benzyloxymethyl-8-(4-cyanomethoxyphenyl)-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione, a compound of formula (7)
	In tetrahydrofuran; ethyl acetate;	e) To a solution of 7-benzyloxymethyl-8-(4-hydroxyphenyl)-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione (1 g, 2.2 mmol) in tetrahydrofuran (20 ml) was added potassium t-butoxide (0.28 g, 2.4 mmol), and the mixture stirred for 30 minutes at room temperature. <strong>[624-75-9]Iodoacetonitrile</strong> (0.38 g, 2.23 mmol) was then added, and the mixture stirred for 16 hours at room temperature. The solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate and passed through a silica gel plug, to provide 7-benzyloxymethyl-8-(4-cyanomethoxyphenyl)-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione, a compound of formula (7)
		e) To a solution of 7-benzyloxymethyl-8-(4-hydroxyphenyl)-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione (1 g, 2.2 mmol) in tetrahydrofuran (20 ml) was added potassium t-butoxide (0.28 g, 2.4 mmol), and the mixture stirred for 30 minutes at room temperature.<strong>[624-75-9]iodoacetonitrile</strong> (0.38 g, 2.23 mmol) was then added, and the mixture stirred for 16 hours at room temperature.The solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate and passed through a silica gel plug, to provide 7-benzyloxymethyl-8-(4-cyanomethoxyphenyl)-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione, a compound of formula (7)

	In tetrahydrofuran; ethyl acetate;	e) To a solution of 7-benzyloxymethyl-8-(4-hydroxyphenyl)-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione (1 g, 2.2 mmol) in tetrahydrofuran (20 ml) was added potassium t-butoxide (0.28 g, 2.4 mmol), and the mixture stirred for 30 minutes at room temperature. <strong>[624-75-9]Iodoacetonitrile</strong> (0.38 g, 2.23 mmol) was then added, and the mixture stirred for 16 hours at room temperature. The solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate and passed through a silica gel plug, to provide 7-benzyloxymethyl-8-(4-cyanomethoxyphenyl)-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione, a compound of formula (7)
		To a solution of 7-BENZYLOXYMETHYL-8- (4-HYDROXYPHENYL)-1, 3-DIPROPYL-1, 3,7- trihydropurine-2,6-dione (LG, 2. 2MMOL) in tetrahydrofuran (20ML) was added potassium t- butoxide (0.28g, 2. 4MMOL), and the mixture stirred for 30 minutes at room temperature. IODOACETONITRILE (0. 38G, 2. 23MMOL) was then added, and the mixture stirred for 16 hours at room temperature. The solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate and passed through a silica gel plug, to provide 7-BENZYLOXYMETHYL-8- (4- cyanomethoxyphenyl)-1, 3-dipropyl-1, 3,7-trihydropurine-2, 6-dione, a compound of formula (7)

Reference： [1]Patent: US2005/261316,2005,A1
[2]Patent: US6977300,2005,B2
[3]Patent: US2003/229106,2003,A1 .Location in patent: Page 23
[4]Patent: US2003/139428,2003,A1
[5]Patent: WO2004/106337,2004,A1 .Location in patent: Page 49

18
[ 624-75-9 ]
[ 119256-40-5 ]
[ 293316-30-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; acetic acid; In ethanol; water;	a (2-Amino-3,5-difluoro-phenylsulfanyl)acetonitrile A suspension of <strong>[119256-40-5]2-amino-4,6-difluoro-benzothiazole</strong> (7.00 g) was stirred for 6 h at 160 C. under nitrogen in a solution of potassium hydroxide (12.6 g) in water (20 ml). The resulting mixture was cooled to 0-5 C. and a solution of acetic acid (8.85 ml) in water (10 ml) and subsequently ethanol (40 ml) and iodoacetonitrile (2.75 ml) were added. After 30 min the mixture was neutralized with acetic acid (2.25 ml) and filtered. The filtrate was evaporated to approx. 30 ml and diluted with water (150 ml). A yellow precipitate was filtered off and dried. The crude product was purified by flash chromatography on silica gel eluted with ethyl acetate-heptane (3:7) yielding the title compound, Rf=0.26, as orange crystals, mp 66-67 C.; 1H-NMR (DMSO-d6), delta (ppm): 7.30-7.07 (m, 2H, Ar-H), 5.33 (br, 2H, NH2), 4.05 (s, 2H, CH2).

Reference： [1]Patent: US6232310,2001,B1

19
[ 20358-07-0 ]
[ 624-75-9 ]
[ 293316-38-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; acetic acid; In ethanol; water;	a (2-Amino-4-fluoro-phenylsulfanyl)acetonitrile A suspension of <strong>[20358-07-0]2-amino-5-fluoro-benzothiazole</strong> (3.45 g) was stirred for 7 h at 165-170 C. under nitrogen in a solution of potassium hydroxide (6.9 g) in water (13.5 ml). The resulting mixture was cooled on an ice bath to 10 C., supplemented with water (5 ml) and then a solution of acetic acid (3.5 ml) in water (4 ml). The mixture was diluted with 96% ethanol (20 ml) and subsequently a solution of iodoacetonitrile (3.42 g) in 96% ethanol (5 ml) was added. After stirring for 15 min the mixture was adjusted to pH ~7 by adding acetic acid and approx. half of the solvent was removed in vacuo. The residue was diluted with water (100 ml) and extracted with ethyl acetate (50+3*25 ml). The combined extracts were dried over sodium sulfate, filtered and evaporated to give the title compound as a practically pure yellow oil. Yield 3.60 g (96%); 1H-NMR (DMSO-d6), delta (ppm): 7.32-7.43 (dd, 1H, Ar-H), 6.49-6.60 (dd, 1H, Ar-H), 6.29-6.43 (ddd, 1H, Ar-H), 5.88 (br, 2H, NH2), 3.82 (s, 2H, CH2).

Reference： [1]Patent: US6232310,2001,B1

20
[ 865305-19-7 ]
[ 624-75-9 ]
[ 865305-20-0 ]

Yield	Reaction Conditions	Operation in experiment
97%		To a solution of 5-chloro-2-isopropyl-4-methoxy-phenol (10.36 g, 51.6 mmol) in 40 mL DMF was added K2CO3 (8.55 g, 62.0 mmol) and the mixture was heated to 65 C. After 15 minutes <strong>[624-75-9]iodoacetonitrile</strong> (9.05 g, 54.2 mmol) was added and the mixture was heated to 80 C. for 1 hour. The mixture was cooled, poured into an ice/H2O mixture and extracted with 1:1 toluene/hexane. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by passing through a short plug of silica to afford (5-chloro-2-isopropyl-4-methoxy-phenoxy)-acetonitrile (11.97 g, 97%) as a white solid.
97%		To a solution of 5-chloro-2-isopropyl-4-methoxy-phenol (10.36 g, 51.6 mmol) in 40 mL DMF was added K2CO3 (8.55 g, 62.0 mmol) and the mixture was heated to 65 C. After 15 minutes <strong>[624-75-9]iodoacetonitrile</strong> (9.05 g, 54.2 mmol) was added and the mixture was heated to 80 C. for 1 hour. The mixture was cooled, poured into an ice/H2O mixture and extracted with 1:1 toluene/hexane. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by passing through a short plug of silica to afford (5-chloro-2-isopropyl-4-methoxy-phenoxy)-acetonitrile (11.97 g, 97%) as a white solid.

Reference： [1]Patent: US2005/209260,2005,A1 .Location in patent: Page/Page column 87
[2]Patent: US2007/49609,2007,A1 .Location in patent: Page/Page column 81
[3]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1628 - 1631

21
[ 624-75-9 ]
6-{(SR)-1-[(3RS,4SR)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile [ No CAS ]
6-{(SR)-1-[(3RS,4SR)-1-(1-cyanomethyl-piperidine-4-carbonyl)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%		Example 346-{(SR)-1-[(3RS,4SR)-1-(1-Cyanomethyl-piperidine-4-carbonyl)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile; To a stirred solution of 6-{(SR)-1-[(3RS,4SR)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile (VIII-B-1) (25 mg, 0.053 mmol) in THF (2 mL) was added NaH (2.4 mg, 55% purity, 0.056 mmol). After 10 min. 2-iodo acetonitrile (13 mg, 0.079 mmol) was added and stirring was continued at RT overnight.The reaction was quenched with H2O, and the product extracted with EtOAc. The combined organic phases were dried over Na2SO4, concentrated under vacuo and the residue was purified by column chromatography (SiO2, CH2Cl2/MeOH 9/1) to yield 20 mg (74%) of the title compound as a light brown foam. ES-MS m/e: 512.0 (M+H+).

Reference： [1]Patent: US2009/306043,2009,A1 .Location in patent: Page/Page column 24

22
[ 624-75-9 ]
4-chloro-N-[(3RS,4SR)-4-(4-chloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-N-methyl-3-trifluoromethyl-benzamide [ No CAS ]
4-chloro-N-[(3RS,4SR)-4-(4-chloro-phenyl)-1-(1-cyanomethyl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-N-methyl-3-trifluoromethyl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%		EXAMPLE 163 4-Chloro-N-[(3RS,4SR)-4-(4-chloro-phenyl)-1-(1-cyanomethyl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-N-methyl-3-trifluoromethyl-benzamide To a solution of 4-chloro-N-[(3RS,4SR)-4-(4-chloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-N-methyl-3-trifluoromethyl-benzamide (216 mg, 0.382 mmol) in DMF (1 mL) was added sodium hydride (55% dispersion in mineral oil, 6 mg, 0.14 mmol). After stirring for 30 min at ambient temperature <strong>[624-75-9]iodoacetonitrile</strong> (9 mul, 0.12 mmol) was added And the suspension was stirred for 18 h at this temperature. After the addition of further <strong>[624-75-9]iodoacetonitrile</strong> (9 mul, 0.12 mmol) the resulting dark brown solution was stirred for further 5 h at ambient temperature. It was diluted with ethyl acetate (10 mL) and was washed with aqueous sodium carbonate (1 M, 10 mL) and brine (10 mL). The aqueous layers were extracted with ethyl acetate (10 mL) and the combined organic phases were dried over sodium sulfate. Purification by chromatography (SiO<SUB>2</SUB>, (ethyl acetate:triethylamine=95:5):methanol=100:0 to 70:30) afforded the title compound (45 mg, 88%) as a white foam. MS m/e: 567.1 [M]<SUP>+</SUP>.

Reference： [1]Patent: US2009/312327,2009,A1 .Location in patent: Page/Page column 65-66

23
[ 624-75-9 ]
[ 1218916-47-2 ]
[ 1218916-49-4 ]

Yield	Reaction Conditions	Operation in experiment
41.4%		EXAMPLE 7 {4-[3-(4-Chlorophenyl)-lH-pyrazolo[4,3-c]pyridin-l-yl]piperidin-l-yl}acetonitrileExample 5 (185 mg, 0.59 mmol) was dissolved in DMF (5 niL) and DIPEA (91.6 mg, 123 muL, 0.71 mmol) and <strong>[624-75-9]iodoacetonitrile</strong> (51.0 muL, 0.71 mmol) were added. The reaction mixture was heated using a Biotage microwave (100 0C, absorption high, pre-stirring 30 sec) for 10 min, and then concentrated in vacuo. The residue was dissolved in MeOH (5 mL), poured into 1 M aq Na2CO3 solution (50 mL) and extracted with EtOAc (3 x 50 mL).The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified by reverse phase HPLC (YMC ODS-A 100 x 20 mm, 5 mum, 25 mL/min, gradient 60% to 100% (over 7 min) then 100% (3 min) MeOH in 10% MeOH/water) to give (4-[3-(4-chlorophenyl)- lH-pyrazolo[4,3-c]pyridin- 1 -yljpiperidin- 1 -yl} acetonitrile (86 mg, 41.4%) as a cream solid.Analytical HPLC: purity 97.9% (System B, Rtau = 4.57 min); Analytical LCMS: purity 100% (System B, Rtau = 4.61 min), ES+: 352.5 [35ClMH]+ and 354.5 [37ClMH]+; HRMS calcd for Ci9Hi8ClN5: 351.1251, found 351.1246

Reference： [1]Patent: WO2010/31791,2010,A1 .Location in patent: Page/Page column 27

24
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 308103-40-4 ]
[ 1192885-55-4 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (320 mg, 0.95 mmol), 2-acetylphenylboronic acid (0.19 g, 1.13 mmol), dichlorobis(triphenylphosphine)palladium(II) (33 mg, 0.05 mmol) and potassium carbonate (131 mg, 0.95 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (152 mg, 61%); m.p. 63-64 C.; 1H NMR (CDCl3) delta 2.19 (s, 3H), 2.28 (s, 3H), 3.70 (s, 3H), 5.16 (s, 2H), 6.75 (s, 1H), 6.79 (s, 1H), 6.90 (s, 1H), 7.11 (d, J=4.1 Hz, 1H), 7.40-7.55 (m, 4H), 7.65 (dd, J=4.8, 7.2 Hz, 1H), 7.81 (s, 1H), 8.48 (d, J=5.1 Hz, 1H).

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-22; 24-25

25
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 308103-40-4 ]
[ 1192885-75-8 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (320 mg, 0.95 mmol), 2-acetylphenyl boronic acid (0.19 g, 1.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (33 mg, 0.05 mmol) and potassium carbonate (131 mg, 0.95 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (102 mg, 82%); m.p. 58-59 C.; 1H NMR (CDCl3) delta 2.19 (s, 3H), 2.39 (s, 3H), 3.79 (s, 3H), 4.95 (s, 2H), 6.72 (s, 1H), 6.79 (s, 1H), 6.92 (s, 1H), 7.06 (d, J=4.3 Hz, 1H), 7.34 (d, J=7.5 Hz, 1H), 7.39-7.48 (m, 4H), 7.98 (s, 1H), 8.43 (d, J=5.1 Hz, 1H); 13C NMR (CDCl3) delta 21.59, 30.48, 37.80, 55.47, 112.20, 114.17, 116.92, 119.23, 119.92, 119.96, 122.67, 127.60, 128.68, 128.93, 128.98, 130.23, 138.65, 139.60, 140.59, 141.46, 141.54, 141.95, 149.48, 157.79, 160.44, 204.11.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-22; 32

26
[ 624-75-9 ]
[ 1192886-16-0 ]
[ 308103-40-4 ]
[ 1192886-20-6 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 64 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and the residue was treated in water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of regioisomers as yellow oil. These two regioisomers (4.16 g, 80%) were used in the next reaction step without separation.Example 65-2Preparation of 4-(2-chloropyridin-5-yl)-5-(3-methoxy-5-methylphenyl)-pyrazol-1-yl)acetonitrile1H NMR (CDCl3) delta 2.28 (s, 3H), 3.66 (s, 3H), 5.16 (s, 2H), 6.71 (s, 2H), 6.84 (s, 1H), 7.24 (d, J=8.3 Hz, 1H), 7.49 (dd, J=2.3, 5.9 Hz, 1H), 7.70 (s, 1H, 8.32 (s, 1H); 13C NMR (CDCl3) delta 21.57, 39.89, 55.23, 110.80, 113.76, 115.28, 117.76, 121.47, 124.02, 127.24, 129.92, 132.57, 138.58, 140.12, 148.71, 149.92, 151.17, 159.69, 162.33.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 65 (400 mg, 1.18 mmol), 2-acetylphenyl boronic acid (023 g, 1.42 mmol), dichlorobis(triphenylphosphine)palladium (II) (41 mg, 0.06 mmol) and potassium carbonate (0.16 g, 1.18 mmol). The reaction system was purged with nitrogen gas for 10 min, and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (155 mg); m.p. 176-177 C.; 1H NMR (CDCl3) delta 2.25 (s, 3H), 2.28 (s, 3H), 3.70 (s, 3H), 5.14 (s, 2H), 6.72 (s, 1H), 6.76 (s, 1H), 6.89 (s, 1H), 7.44-7.65 (m, 6H), 7.70 (s, 1H), 8.54 (s, 1H); 13C NMR (CDCl3) delta 21.51, 30.58, 39.79, 55.19, 110.80, 113.82, 115.30, 118.66, 121.54, 121.89, 127.06, 127.63, 128.80, 128.96, 130.02, 130.36, 132.92, 136.56, 138.15, 139.93, 141.68, 148.55, 151.23, 155.76, 159.71, 204.39.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 50; 52

27
[ 624-75-9 ]
[ 1192886-16-0 ]
[ 308103-40-4 ]
[ 1192886-23-9 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 64 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and the residue was treated in water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of regioisomers as yellow oil. These two regioisomers (4.16 g, 80%) were used in the next reaction step without separation.Example 65-2Preparation of 4-(2-chloropyridin-5-yl)-5-(3-methoxy-5-methylphenyl)-pyrazol-1-yl)acetonitrile1H NMR (CDCl3) delta 2.28 (s, 3H), 3.66 (s, 3H), 5.16 (s, 2H), 6.71 (s, 2H), 6.84 (s, 1H), 7.24 (d, J=8.3 Hz, 1H), 7.49 (dd, J=2.3, 5.9 Hz, 1H), 7.70 (s, 1H, 8.32 (s, 1H); 13C NMR (CDCl3) delta 21.57, 39.89, 55.23, 110.80, 113.76, 115.28, 117.76, 121.47, 124.02, 127.24, 129.92, 132.57, 138.58, 140.12, 148.71, 149.92, 151.17, 159.69, 162.33.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 65 (0.3 g, 0.89 mmol), 2-acetylphenylboronic acid (0.18 g, 1.07 mmol), dichlorobis(triphenylphosphine)palladium (II) (32 mg, 0.05 mmol) and potassium carbonate(0.13 g, 0.89 mmol). The reaction system was purged with nitrogen gas for 10 min, and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (72 mg); m.p. 72-73 C.; 1H NMR (CDCl3) delta 2.18 (s, 3H), 2.36 (s, 3H), 3.78 (s, 3H), 4.95 (s, 2H), 6.68 (s, 1H), 6.75 (s, 1H), 6.86 (s, 1H), 7.43-7.59 (m, 6H), 7.91 (s, 1H), 8.49 (s, 1H); 13C NMR (CDCl3) delta 21.55, 30.49, 37.81, 55.38, 112.37, 114.78, 116.72, 118.33, 122.13, 122.67, 126.78, 127.62, 128.64, 128.92, 128.99, 130.26, 134.89, 138.22, 139.49, 141.23, 141.33, 141.58, 147.50, 155.33, 160.40, 204.23.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 50; 54

28
[ 624-75-9 ]
[ 1192885-45-2 ]
3-acetylphenylboronic acid [ No CAS ]
[ 1192885-57-6 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (320 mg, 0.95 mmol), 3-acetylphenyl boronic acid (0.19 g, 1.13 mmol), thchlorobis(triphenylphosphine)palladium (II) (33 mg, 0.05 mmol) and potassium carbonate (131 mg, 0.95 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (197 mg, 79%); m.p. 73-74 C.; 1H NMR (CDCl3) delta 2.27 (s, 3H), 2.60 (s, 3H), 3.67 (s, 3H), 5.19 (s, 2H), 6.76 (s, 1H), 6.80 (s, 1H), 6.91 (s, 1H), 7.13 (s, 1H), 7.49 (bs, 1H), 7.64 (s, 1H), 7.85 (s, 1H), 7.95 (d, J=5.4 Hz, 1H), 8.04 (d, J=5.7 Hz, 1H), 8.39 (s, 1H), 8.56 (s, 1H); 13C NMR (CDCl3) delta 21.51, 26.78, 39.89, 55.23, 111.03, 113.93, 115.51, 119.76, 119.90, 121.63, 121.77, 126.71, 128.60, 128.76, 129.11, 130.54, 131.45, 132.06, 132.92, 137.52, 139.61, 140.00, 141.09, 149.91, 151.38, 156.47, 159.69, 198.16.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-22; 25-26

29
[ 624-75-9 ]
[ 1192885-45-2 ]
3-acetylphenylboronic acid [ No CAS ]
[ 1192885-76-9 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (320 mg, 0.95 mmol), 3-acetylphenylboronic acid (0.19 g, 1.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (33 mg, 0.05 mmol) and potassium carbonate (131 mg, 0.95 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (96 mg, 77%); m.p. 65-66 C.; 1H NMR (CDCl3) delta 2.39 (s, 3H), 2.62 (s, 3H), 3.79 (s, 3H), 4.96 (s, 2H), 6.74 (s, 1H), 6.80 (s, 1H), 6.95 (s, 1H), 7.10 (bs, 1H), 7.50 (t, J=7.5 Hz, 1H), 7.56 (s, 1H), 7.94-8.00 (m, 3H), 8.29 (s, 1H), 8.52 (d, J=4.2 Hz, 1H); 13C NMR (CDCl3) delta 21.59, 26.78, 37.77, 55.78, 112.33, 114.14, 116.93, 118.18, 119.32, 120.14, 122.64, 126.60, 128.68, 129.01, 131.39, 137.53, 139.59, 139.72, 140.66, 141.54, 141.93, 150.05, 156.54, 160.45, 197.89.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-22; 32-33

30
[ 624-75-9 ]
[ 1192886-16-0 ]
3-acetylphenylboronic acid [ No CAS ]
[ 1192886-21-7 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 64 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and the residue was treated in water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of regioisomers as yellow oil. These two regioisomers (4.16 g, 80%) were used in the next reaction step without separation.Example 65-2Preparation of 4-(2-chloropyridin-5-yl)-5-(3-methoxy-5-methylphenyl)-pyrazol-1-yl)acetonitrile1H NMR (CDCl3) delta 2.28 (s, 3H), 3.66 (s, 3H), 5.16 (s, 2H), 6.71 (s, 2H), 6.84 (s, 1H), 7.24 (d, J=8.3 Hz, 1H), 7.49 (dd, J=2.3, 5.9 Hz, 1H), 7.70 (s, 1H, 8.32 (s, 1H); 13C NMR (CDCl3) delta 21.57, 39.89, 55.23, 110.80, 113.76, 115.28, 117.76, 121.47, 124.02, 127.24, 129.92, 132.57, 138.58, 140.12, 148.71, 149.92, 151.17, 159.69, 162.33.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 65 (320 mg, 0.95 mmol), 3-acetylphenylboronic acid (0.19 g, 1.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (33 mg, 0.04 mmol) and potassium carbonate (0.13 g, 0.95 mmol). The reaction system was purged with nitrogen gas for 10 min, and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (202 mg); m.p. 73-74 C.; 1H NMR (CDCl3) delta 2.27 (s, 3H), 2.65 (s, 3H), 3.66 (s, 3H), 5.16 (s, 2H), 6.71 (s, 1H), 6.77 (s, 1H), 6.91 (s, 1H), 7.54 (t, J=7.7 Hz, 1H), 7.60-7.72 (m, 3H), 8.97 (d, J=7.5 Hz, 1H), 8.19 (d, J=7.5 Hz, 1H), 8.58 (s, 1H), 8.63 (s, 1H); 13C NMR (CDCl3) delta 21.55, 26.83, 39.84, 55.19, 110.91, 113.92, 115.23, 118.77, 120.03, 121.58, 126.53, 127.18, 128.77, 129.14, 129.93, 131.22, 133.02, 136.57, 137.63, 139.31, 139.97, 149.01, 151.22, 154.56, 159.68, 198.12.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 50; 52-53

31
[ 624-75-9 ]
[ 1192886-16-0 ]
3-acetylphenylboronic acid [ No CAS ]
[ 1192886-24-0 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 64 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and the residue was treated in water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of regioisomers as yellow oil. These two regioisomers (4.16 g, 80%) were used in the next reaction step without separation.Example 65-2Preparation of 4-(2-chloropyridin-5-yl)-5-(3-methoxy-5-methylphenyl)-pyrazol-1-yl)acetonitrile1H NMR (CDCl3) delta 2.28 (s, 3H), 3.66 (s, 3H), 5.16 (s, 2H), 6.71 (s, 2H), 6.84 (s, 1H), 7.24 (d, J=8.3 Hz, 1H), 7.49 (dd, J=2.3, 5.9 Hz, 1H), 7.70 (s, 1H, 8.32 (s, 1H); 13C NMR (CDCl3) delta 21.57, 39.89, 55.23, 110.80, 113.76, 115.28, 117.76, 121.47, 124.02, 127.24, 129.92, 132.57, 138.58, 140.12, 148.71, 149.92, 151.17, 159.69, 162.33.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 65 (0.32 g, 0.95 mmol), 3-acetylphenylboronic acid (0.19 g, 1.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (33 mg, 0.04 mmol) and potassium carbonate (0.13 g, 0.95 mmol). The reaction system was purged with nitrogen gas for 10 min, and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (106 mg); m.p. 149-150 C.; 1H NMR (CDCl3) delta 2.37 (s, 3H), 2.67 (s, 3H), 3.78 (s, 3H), 4.95 (s, 2H), 6.71 (s, 1H), 6.77 (s, 1H), 6.87 (s, 1H), 7.51-7.70 (m, 3H), 7.92 (s, 1H), 7.97 (d, J=7.6 Hz, 1H), 8.16 (d, J=7.8 Hz, 1H), 8.53 (s, 1H), 8.57 (d, J=1.2 Hz, 1H); 13C NMR (CDCl3) delta 21.61, 26.82, 37.80, 55.41, 112.41, 114.22, 116.66, 118.39, 120.33, 122.71, 126.53, 126.96, 128.67, 129.04, 129.09, 131.18, 135.01, 137.58, 139.36, 139.48, 141.15, 141.36, 147.96, 154.21, 160.37, 198.06.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 50; 54-55

32
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 149104-90-5 ]
[ 1192885-59-8 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (320 mg, 0.95 mmol), 4-acetylphenyl boronic acid (0.19 g, 1.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (33 mg, 0.05 mmol) and potassium carbonate (131 mg, 0.95 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (170 mg, 68%); m.p. 99-100 C.; 1H NMR (CDCl3) delta 2.32 (s, 3H), 2.65 (s, 3H), 3.72 (s, 3H), 5.20 (s, 2H), 6.79 (s, 1H), 6.82 (s, 1H), 6.94 (s, 1H), 7.20 (d, J=5.1 Hz, 1H), 7.69 (s, 1H), 7.88 (s, 1H), 7.95 (d, J=8.4 Hz, 2H), 8.02 (d, J=8.4 Hz, 2H), 8.63 (d, J=5.1 Hz, 1H); 13C NMR (CDCl3) delta 21.54, 26.80, 39.95, 55.27, 110.97, 113.53, 115.58, 120.20, 121.74, 121.88, 127.00, 128.82, 130.02, 132.77, 137.19, 140.06, 140.95, 143.39, 150.15, 151.54, 156.35, 159.77, 197.91.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-22; 26

33
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 149104-90-5 ]
[ 1192885-78-1 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (320 mg, 0.95 mmol), 4-acetylphenyl boronic acid (0.19 g, 1.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (33 mg, 0.05 mmol) and potassium carbonate (131 mg, 0.95 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (93 mg, 75%); m.p. 156-157 C.; 1H NMR (CDCl3) delta 2.42 (s, 3H), 2.65 (s, 3H), 3.82 (s, 3H), 4.97 (s, 2H), 6.75 (s, 1H), 6.82 (s, 1H), 6.96 (s, 1H), 7.12 (d, J=4.9 Hz, 1H), 7.60 (s, 1H), 7.87 (d, J=8.1 Hz, 2H), 7.99-8.02 (m, 3H), 8.56 (d, J=5.1 Hz, 1H); 13C NMR (CDCl3) delta 21.60, 26.78, 37.78, 55.52, 112.34, 114.02, 116.86, 118.62, 119.33, 120.38, 122.67, 126.90, 128.76, 129.01, 137.12, 139.56, 140.61, 141.58, 141.96, 143.49, 150.20, 156.29, 160.54, 197.88.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-22; 33-34

34
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 1692-25-7 ]
[ 1192885-53-2 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of acetonitrile and water (4:1, 10 mL) were added the mixture prepared in Example 22 (100 mg, 0.30 mmol), 3-pyridineboronic acid (40.5 mg, 0.33 mmol), dichlorobis(triphenylphosphine)palladium (II) (10 mg, 0.015 mmol) and potassium carbonate (41 mg, 0.295 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 2:1, v/v): (180 mg, 80%); m.p. 72-73 C.; 1H NMR (CDCl3) delta 2.28 (s, 3H), 3.69 (s, 3H), 5.17 (s, 2H), 6.76 (s, 1H), 6.80 (s, 1H), 6.91 (s, 1H), 7.17 (dd, J=1.2, 3.9 Hz, 1H), 7.35 (dd, J=2.7, 4.8 Hz, 1H), 7.62 (s, 1H), 7.84 (s, 1H), 8.18 (d, J =8.1 Hz, 1H), 8.56-8.60 (m, 2H), 9.00 (d, J=1.3 Hz, 1H) 13C NMR (CDCl3) delta 21.50, 39.91, 55.25, 111.12, 113.66, 115.49, 119.72, 119.98, 121.72, 121.80, 123.61, 130.20, 132.77, 134.33, 134.72, 140.03, 141.06, 148.11, 149.94, 150.25, 151.48, 155.00, 159.75.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-24

35
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 1692-25-7 ]
[ 1192885-73-6 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (300 mg, 0.89 mmol), 3-pyridineboronic acid (0.13 g, 1.06 mmol), dichlorobis(triphenylphosphine)palladium (II) (31 mg, 0.04 mmol) and potassium carbonate (130 mg, 0.89 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 2:1, v/v): (62 mg, 55%); m.p. 81-82 C.; 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.80 (s, 3H), 4.95 (s, 2H), 6.73 (s, 1H), 6.80 (s, 1H), 6.94 (s, 1H), 7.11 (d, J=5.0 Hz, 1H), 7.34 (dd, J=3.0, 4.8 Hz, 1H), 7.54 (s, 1H), 8.00 (s, 1H), 8.15 (d, J=7.8 Hz, 1H), 8.54 (d, J=5.1 Hz, 1H), 8.60 (d, J=4.4 Hz, 1H), 8.89 (s, 1H); 13C NMR (CDCl3) delta 21.62, 37.79, 55.50, 112.38, 114.08, 116.81, 118.15, 119.21, 120.35, 122.59, 123.59, 128.90, 134.30, 134.78, 139.57, 140.71, 141.57, 141.97, 148.02, 149.92, 150.34, 154.99, 160.48.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-23; 31-32

36
[ 624-75-9 ]
[ 1192886-16-0 ]
[ 1692-25-7 ]
[ 1192886-19-3 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 64 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and the residue was treated in water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of regioisomers as yellow oil. These two regioisomers (4.16 g, 80%) were used in the next reaction step without separation.Example 65-2Preparation of 4-(2-chloropyridin-5-yl)-5-(3-methoxy-5-methylphenyl)-pyrazol-1-yl)acetonitrile1H NMR (CDCl3) delta 2.28 (s, 3H), 3.66 (s, 3H), 5.16 (s, 2H), 6.71 (s, 2H), 6.84 (s, 1H), 7.24 (d, J=8.3 Hz, 1H), 7.49 (dd, J=2.3, 5.9 Hz, 1H), 7.70 (s, 1H, 8.32 (s, 1H); 13C NMR (CDCl3) delta 21.57, 39.89, 55.23, 110.80, 113.76, 115.28, 117.76, 121.47, 124.02, 127.24, 129.92, 132.57, 138.58, 140.12, 148.71, 149.92, 151.17, 159.69, 162.33.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 65 (0.3 g, 0.89 mmol), 3-pyridineboronic acid (0.13 g, 1.07 mmol), dichlorobis(triphenylphosphine)palladium (II) (32 mg, 0.05 mmol) and potassium carbonate (0.13 g, 0.89 mmol). The reaction system was purged with nitrogen gas for 10 min, and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:3, v/v): (176 mg); m.p. 66-67 C.; 1H NMR (CDCl3) delta 2.27 (s, 3H), 3.67 (s, 3H), 5.16 (s, 2H), 6.71 (s, 1H), 6.76 (s, 1H), 6.90 (s, 1H), 7.36-7.40 (m, 1H), 7.62-7.69 (m, 2H), 7.73 (s, 1H), 8.29 (d, J=7.7 Hz, 1H), 8.62-8.65 (m, 2H), 9.19 (s, 1H); 13C NMR (CDCl3) delta 21.51, 39.85, 55.18, 110.91, 113.73, 115.30, 118.78, 119.96, 121.57, 123.62, 127.41, 129.76, 132.92, 134.10, 134.35, 136.58, 139.97, 148.09, 149.28, 149.93, 151.30,153.13, 159.71.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 50-51

37
[ 624-75-9 ]
[ 1192886-16-0 ]
[ 1692-25-7 ]
[ 1192886-22-8 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 64 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and the residue was treated in water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of regioisomers as yellow oil. These two regioisomers (4.16 g, 80%) were used in the next reaction step without separation.Example 65-2Preparation of 4-(2-chloropyridin-5-yl)-5-(3-methoxy-5-methylphenyl)-pyrazol-1-yl)acetonitrile1H NMR (CDCl3) delta 2.28 (s, 3H), 3.66 (s, 3H), 5.16 (s, 2H), 6.71 (s, 2H), 6.84 (s, 1H), 7.24 (d, J=8.3 Hz, 1H), 7.49 (dd, J=2.3, 5.9 Hz, 1H), 7.70 (s, 1H, 8.32 (s, 1H); 13C NMR (CDCl3) delta 21.57, 39.89, 55.23, 110.80, 113.76, 115.28, 117.76, 121.47, 124.02, 127.24, 129.92, 132.57, 138.58, 140.12, 148.71, 149.92, 151.17, 159.69, 162.33.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 65 (0.3 g, 0.89 mmol), 3-pyridineboronic acid (0.13 g, 1.07 mmol), dichlorobis(triphenylphosphine)palladium (II) (32 mg, 0.05 mmol) and potassium carbonate (0.13 g, 0.89 mmol). The reaction system was purged with nitrogen gas for 10 min, and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:3, v/v): (87 mg); m.p. 64-65 C.; in NMR (CDCl3) delta 2.37 (s, 3H), 3.79 (s, 3H), 4.94 (s, 2H), 6.71 (s, 1H), 6.77 (s, 1H), 6.88 (s, 1H), 7.36-7.40 (m, 1H), 7.60-7.67 (m, 2H), 7.92 (s, 1H), 8.27 (d, J=7.7 Hz, 1H), 8.60-8.62 (m, 2H), 9.15 (s, 1H); 13C NMR (CDCl3) delta 21.60, 37.81, 55.41, 112.42, 114.14, 116.71, 118.30, 120.26, 122.69, 123.62, 127.25, 128.99, 134.09, 134.43, 135.01, 139.48, 141.21, 141.39, 147.98, 148.25, 149.80, 152.64, 160.40.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 50; 53-54

38
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 98-80-6 ]
[ 1192885-51-0 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (300 mg, 0.89 mmol), phenylboronic acid (0.12 g, 0.974 mmol), dichlorobis(triphenylphosphine)palladium (II) (31 mg, 0.044 mmol) and potassium carbonate (130 mg, 0.89 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:3, v/v): (166 mg, 74%); m.p. 55-56 C; 1H NMR (CDCl3) delta 2.32 (s, 3H), 3.71 (s, 3H), 5.14 (s, 2H), 6.79 (s, 1H), 6.84 (s, 1H), 6.96 (s, 1H), 7.13 (d, J=4.9 Hz, 1H), 7.41-7.48 (m, 3H), 7.65 (s, 1H), 7.79 (s, 1H), 7.88 (d, J=6.9 Hz, 2H), 8.61 (d, J=5.1 Hz, 1H); 13C NMR (CDCl3) delta21.51, 39.86, 55.25, 110.90, 113.61, 115.61, 119.78, 120.42, 121.24, 121.76, 126.89, 128.78, 129.11, 130.05, 132.90, 139.19, 139.98, 140.77, 149.89, 151.46, 157.75, 159.75.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-23

39
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 98-80-6 ]
[ 1192885-71-4 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (100 mg, 0.30 mmol), phenylboronic acid (43.9 mg, 0.36 mmol), dichlorobis(triphenylphosphine)palladium (II) (11 mg, 0.02 mmol) and potassium carbonate (42 mg, 0.30 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:3, v/v): (70 mg, 62%); m.p. 51-52 C.; 1H NMR (CDCl3) delta 2.41 (s, 3H), 3.81 (s, 3H), 4.95 (s, 2H), 6.76 (s, 1H), 6.82 (s, 1H), 6.95 (s, 1H), 7.06 (d, J=4.5 Hz, 1H), 7.41-7.44 (m, 3H), 7.58 (s, 1H), 7.80 (d, J=6.3 Hz, 2H), 8.01 (s, 1H), 8.53 (d, J=4.8 Hz, 1H) 13C NMR (CDCl3) delta 21.57, 37.76, 55.49, 112.31, 114.07, 116.90, 118.29, 119.60, 119.70, 122.75, 126.83, 128.71, 129.03, 129.11, 139.21, 139.61, 140.45, 141.47, 141.89, 149.88, 157.70, 160.51.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-22; 30-31

40
[ 624-75-9 ]
[ 1192885-45-2 ]
[ 28611-39-4 ]
[ 1192885-67-8 ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added <strong>[624-75-9]iodoacetonitrile</strong> (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (320 mg, 0.95 mmol), 4-(dimethylaniino)phenylboronic acid (0.19 g, 1.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (34 mg, 0.05 mmol) and potassium carbonate (131 mg, 0.95 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 1:2, v/v): (197 mg, 79%); m.p. 98-99 C.; 1H NMR (CDCl3) delta 2.31 (s, 3H), 3.01 (s, 6H), 3.70 (s, 3H), 5.10 (s, 2H), 6.75-6.78 (m, 3H), 6.84 (s, 1H), 6.97-7.00 (m, 2H), 7.56 (s, 1H), 7.72 (s, 1H), 7.80 (d, J=8.8 Hz, 2H), 8.52 (d, J=5.0 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.79, 40.34, 55.25, 110.68, 112.16, 113.70, 115.67, 118.33, 119.88, 120.69, 121.74, 126.77, 127.72, 130.10, 132.99, 139.89, 140.46, 149.55, 151.13, 151.35, 157.78, 159.68.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 21-22; 29

41
[ 950525-67-4 ]
[ 624-75-9 ]
[ 1262110-33-7 ]

Yield	Reaction Conditions	Operation in experiment
37.4%	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 16h;	In a two-necked round-bottom flask, [3-(3-methoxy-5-methylphenyl)-4-(2-methylthiopyrimidine-4-yl]-1H-pyrazol (5 g, 16.0 mmol) was dissolved in dimethylformamide (65 mL) to which potassium carbonate (5.52 g, 40 mmol) and <strong>[624-75-9]iodoacetonitrile</strong> (2.9 mL, 40 mmol) were added, and heated at 50 C. for 16 hours with stirring. After completion of the reaction, the reaction mixture was washed with brine and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed by vacuum distillation and the residue was purified through column chromatography to recover the title compound (2.1 g, 37.4%).m.p. 117 C.; 1H NMR (400 MHz, CDCl3) delta 2.36 (s, 3H), 2.54 (s, 3H), 3.78 (s, 3H), 5.15 (s, 2H), 6.79 (s, 1H), 6.80 (s, 1H), 6.82 (d, J=4.79 Hz, 1H), 6.92 (s, 1H), 8.26 (s, 1H), 8.30 (d, J=5.22 Hz, 1H); IR (KBr) 3429, 2926, 1571, 1460, 1324, 1157 cm-1.

Reference： [1]Patent: US2011/15395,2011,A1 .Location in patent: Page/Page column 17-18

42
[ 624-75-9 ]
[ 1315544-56-9 ]
[ 1315544-57-0 ]

Yield	Reaction Conditions	Operation in experiment
67%	With caesium carbonate; In N,N-dimethyl-formamide; at 110℃; for 42h;	As shown in step 5-ii of Scheme 5, 5-bromo-2-(lH-pyrazol-4-yl)isoindolin-l-one (1.2 g, 4.32 mmol) was combined with cesium carbonate (1.69 g, 5.18 mmol) in DMF (10 mL) in a sealable tube and nitrogen gas was bubbled through the solution for 5 minutes. 2- <strong>[624-75-9]Iodoacetonitrile</strong> (1.08 g, 468 mu, 6.47 mmol) was added and the tube was sealed and heated to 110 C in an oil bath for 18 hours. Additional <strong>[624-75-9]iodoacetonitrile</strong> added (0.5 mL) and the reaction mixture was heated for an additional 24 hours. The reaction mixture was poured into H20/EtOAc and the resulting dark brown solid was collected by filtration. The solid was washed with MeOH and then diethyl ether to provide 2-[4-(5-bromo-l-oxo-isoindolin-2- yl)pyrazol-l-yl]acetonitrile (Compound 2020, 920 mg, 2.9 mmol, 67% yield): ESMS (M+H) 319.04; 1H NMR (DMSO-d6) delta 8.35 (s, 1H), 7.92 (m, 2H), 7.70 (m, 2H), 5.53 (s, 2H), 4.88 (s, 2H).

Reference： [1]Patent: WO2011/87776,2011,A1 .Location in patent: Page/Page column 57; 58

43
[ 624-75-9 ]
[ 87281-44-5 ]
[ 1346672-94-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	With ferrous(II) sulfate heptahydrate; dihydrogen peroxide; at 20 - 35℃;	A 500-mL three-neck round-bottomed flask equipped with an addition funnel, thermometer and charged with 118a (6.70 g, 37.4 mmol), <strong>[624-75-9]Iodoacetonitrile</strong> (12.5 g, 74.9 mmol), iron (II) sulfate heptahydrate (5.20 g, 18.7 mmol) and dimethyl sulfoxide (250 mL). Hydrogen peroxide (35%, 18.2 g, 187 mmol) was added dropwise to the mixture in 1 h through a syringe pump at room temperature using a water bath. Iron (II) sulfateheptahydrate (2 to 3 equivalent) was added to the reaction mixture in portions to keep the temperature between 25 C to 35 C, until the color of the reaction mixture is deep red. If TLC show the reaction not completed, then more hydrogen peroxide (2-3 equivalent) and more iron (II) sulfate heptahydrate (1-2 equivalent) were added in the same manner until the reaction is completed. After that time, the reaction mixture was partitioned between saturated sodium bicarbonate solution (200 mL) and ethyl acetate (400 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with saturated Sodium thiosulfate solution (50 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 78% yield (6.40 g) of 118b as a yellow oil: ]H NMR (500 MHz, CDC13) delta 6.23 (s, 1H), 4.23 (s, 2H), 3.94 (t, 2H, J = 6.5 Hz), 3.81 (s, 3H), 2.74 (t, 2H, J = 6.5 Hz), 2.00 (m, 2H), 1.83 (m, 2H); (APCI+) m/z 219.3 (M+H)
78%	With ferrous(II) sulfate heptahydrate; dihydrogen peroxide; at 20 - 35℃;	Example 101e Methyl 3-(Cyanomethyl)-5,6,7,8-tetrahydroindolizine-2-carboxylate 101e A 500-mL three-neck round-bottomed flask equipped with an addition funnel, thermometer and charged with methyl 5,6,7,8-tetrahydroindolizine-2-carboxylate 101d (6.70 g, 37.4 mmol), <strong>[624-75-9]iodoacetonitrile</strong> (12.5 g, 74.9 mmol), iron (II) sulfate heptahydrate (5.20 g, 18.7 mmol) and dimethyl sulfoxide (250 mL). Hydrogen peroxide (35%, 18.2 g, 187 mmol) was added dropwise to the mixture in 1 h through a syringe pump at room temperature using a water bath. Iron (II) sulfate heptahydrate (2 to 3 equivalent) was added to the reaction mixture in portions to keep the temperature between 25 C. to 35 C., until the color of the reaction mixture is deep red. If TLCs show the reaction not completed, then more hydrogen peroxide (2-3 equivalent) and more iron (II) sulfate heptahydrate (1-2 equivalent) were added in the same manner until the reaction is completed. After that time, the reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution (200 mL) and ethyl acetate (400 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2*100 mL). The combined organic layers were washed with saturated Sodium thiosulfate solution (50 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 78% yield (6.40 g) of 101e as a yellow oil: 1H NMR (500 MHz, CDCl3) delta 6.23 (s, 1H), 4.23 (s, 2H), 3.94 (t, 2H, J=6.5 Hz), 3.81 (s, 3H), 2.74 (t, 2H, J=6.5 Hz), 2.00 (m, 2H), 1.83 (m, 2H); (APCI+) m/z 219.3 (M+H)
78%	With ferrous(II) sulfate heptahydrate; dihydrogen peroxide; In dimethyl sulfoxide; at 20 - 35℃;	A 500-mL three-neck round-bottomed flask equipped with an addition funnel, thermometer and charged with 120a (6.70 g, 37.4 mmol), <strong>[624-75-9]iodoacetonitrile</strong> (12.5 g, 74.9 mmol), iron (II) sulfate heptahydrate (5.20 g, 18.7 mmol) and dimethyl sulfoxide (250 mL). Hydrogen peroxide (35%, 18.2 g, 187 mmol) was added dropwise to the mixture over the period of 1 h through a syringe pump at room temperature using a water bath. Iron (II) sulfate heptahydrate (2 to 3 equivalent) was added to the reaction mixture in portions to keep the temperature between 25 C. to 35 C., until the color of the reaction mixture was deep red. When TLCs showed the reaction was not complete, more hydrogen peroxide (2-3 equivalent) and more iron (II) sulfate heptahydrate (1-2 equivalents) were added in the same manner until the reaction was complete. After that time, the reaction mixture was partitioned between saturated sodium bicarbonate solution (200 mL) and ethyl acetate (400 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2*100 mL). The combined organic layers were washed with saturated sodium thiosulfate solution (50 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 78% yield (6.40 g) of 120b as a yellow oil: 1H NMR (500 MHz, CDCl3) delta 6.23 (s, 1H), 4.23 (s, 2H), 3.94 (t, 2H, J=6.5 Hz), 3.81 (s, 3H), 2.74 (t, 2H, J=6.5 Hz), 2.00 (m, 2H), 1.83 (m, 2H); (APCI+) m/z 219.3 (M+H)

78%

With ferrous(II) sulfate heptahydrate; dihydrogen peroxide; In dimethyl sulfoxide; at 25 - 35℃;

Example 112b Methyl 3-(Cyanomethyl)-5,6,7,8-tetrahydroindolizine-2-carboxylate 112b A 500-mL three-neck round-bottomed flask equipped with an addition funnel, thermometer and charged with 112a (6.70 g, 37.4 mmol), [624-75-9]Iodoacetonitrile (12.5 g, 74.9 mmol), iron (II) sulfate heptahydrate (5.20 g, 18.7 mmol) and dimethyl sulfoxide (250 mL). Hydrogen peroxide (35%, 18.2 g, 187 mmol) was added dropwise to the mixture in 1 h through a syringe pump at room temperature using a water bath. Iron (II) sulfate heptahydrate (2 to 3 equivalent) was added to the reaction mixture in portions to keep the temperature between 25 C to 35 C, until the color of the reaction mixture is deep red. If TLC shows the reaction not completed, then more hydrogen peroxide (2-3 equivalent) and more iron (II) sulfate heptahydrate (1-2 equivalent) are added in the same manner until the reaction is completed. After that time, the reaction mixture was partitioned between saturated sodium bicarbonate solution (200 mL) and ethyl acetate (400 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2 * 100 mL). The combined organic layers were washed with saturated Sodium thiosulfate solution (50 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 78% yield (6.40 g) of 112b as a yellow oil: 1H NMR (500 MHz, CDCl3) delta 6.23 (s, 1H), 4.23 (s, 2H), 3.94 (t, 2H, J = 6.5 Hz), 3.81 (s, 3H), 2.74 (t, 2H, J = 6.5 Hz), 2.00 (m, 2H), 1.83 (m, 2H); (APCI+) m/z 219.3 (M+H)

Reference： [1]Patent: WO2011/140488,2011,A1 .Location in patent: Page/Page column 111; 164; 165
[2]Patent: US2013/116245,2013,A1 .Location in patent: Paragraph 0194
[3]Patent: US2013/116262,2013,A1 .Location in patent: Paragraph 0349; 0350; 0351
[4]Patent: EP2773638,2015,B1 .Location in patent: Paragraph 0262; 0263

44
[ 624-75-9 ]
[ 1234619-70-5 ]
[ 1234619-73-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With 18-crown-6 ether; potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h;	Example 41 Benzyl {(7R)-6-cyano-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}(cyanomethyl)carbamate Potassium carbonate (15.7 mg, 113 mmol, 2.1 eq.), 18-crown-6 (30 mg, 113 mmol, 2.1 eq.) and <strong>[624-75-9]iodoacetonitrile</strong> (19 mg, 113 mmol, 2.1 eq.) were added to a solution of benzyl {(7R)-6-cyano-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}carbamate (30 mg, 54 mmol) in DMF (2 ml). The reaction mixture was stirred at RT for 12 h and then concentrated under reduced pressure. The residue was acidified with acetic acid and then purified by preparative HPLC (Kromasil C18 column, 5 mum, 50*20 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (25 mg, 78% of theory). LC-MS (Method 5): Rt=1.40 min; MS (ESIpos): m/z (%)=434.0 (100), 550.9 (20), 595.0 (30) [M+H]+; MS (ESIneg): m/z (%)=593.8 (100) [M-H]-. 1H-NMR (400 MHz, DMSO-d6): delta=2.00 (s, 3H), 4.55 (d, 2H), 5.10 (d, 2H), 6.55 (s, 1H), 7.15-7.35 (m, 5H), 7.70-7.95 (m, 7H), 8.15 (br. s, 1H).

Reference： [1]Patent: US2012/4203,2012,A1 .Location in patent: Page/Page column 51

45
[ 624-75-9 ]
[ 59279-60-6 ]
[ 328086-57-3 ]

Reference： [1]Science China Chemistry,2012,vol. 55,p. 1101 - 1107

46
[ 624-75-9 ]
[ 50-89-5 ]
[ 1425376-84-6 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium carbonate; In N,N-dimethyl-formamide; acetone; for 6h;Reflux;	Thymidine (10 g, 41.3 mmol) and potassium carbonate (17 g, 123 mmol) were dissolved in acetone/ DMF (100 mL, 1/1, v/v) and iodoacetonitile (6.5 mL, 90 mmol) was added. The reaction mixture was refluxed for 6 h, then added to water (750 mL), and extracted with ethyl acetate (250 mL × 4). The organic layer was separated, dried using anhydrous magnesium sulphate (100 g), evaporated under reduced pressure, and purified by silica gel column chromatography using dichloromethane and methanol as the solvent system. The compound was eluted at 4% methanol. Rf = 0.70 (10% methanol in dichloromethane), yield = 9.1 g, 78% as yellow solid, (m.p. 52 C); 1H NMR (400 MHz, CD3OD, delta ppm): 7.86 (s, 1H, H-6), 6.25 (t, J = 6.6 Hz, 1H, 1?H), 4.80 (s, 2H, CH2-CN), 4.33-4.41 (m, 1H, 3?H), 3.87-3.95 (m, 1H, 4?H), 3.78 (dd, J = 2.8 and 12.0 Hz, 2H, 5?H), 3.70 (dd, J = 3.1 and 12.0 Hz, 2H, 5?H), 2.23-2.33 (m, 1H, 2?H), 2.12-2.22 (m, 1H, 2?H), 1.89 (s, 3H, 5-CH3). 13C NMR (CD3OD, 100 MHz, delta ppm): 163.29 (C-4 C=O), 150.62 (C-2 C=O), 136.77 (C-6), 115.46 (CN), 110.30 (C-5), 88.27 (C-1?), 86.79 (C-4?), 71.40 (C-3?), 62.16 (C-5?), 41.09 (C-2?), 28.92 (N3-CH2-CN), 13.05 (5-CH3); HR-MS (ESI-MS) for C12H15N3NaO5. Calcd: 304.0909. Found: m/z 304.0888 (M + Na)+.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 60,p. 456 - 468
[2]European Journal of Medicinal Chemistry,2015,vol. 100,p. 197 - 209

47
[ 624-75-9 ]
8-chloro-3-(5-chloro-2-ethanesulfonylbenzyl)-7-piperazin-1-ylmethyl-6-trifluoromethyl-1H-quinazoline-2,4-dione [ No CAS ]
{4-[8-chloro-3-(5-chloro-2-ethanesulfonylbenzyl)-2,4-dioxo-6-trifluoromethyl-1,2,3,4-tetrahydroquinazolin-7-ylmethyl]piperazin-1-yl}acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-ethyl-N,N-diisopropylamine; In chloroform; at 20 - 25℃; for 23h;	<strong>[624-75-9]Iodoacetonitrile</strong> (4.30 mul, 0.059 mmol) was added to a solution of 8-chloro-3-(5-chloro-2-ethanesulfonyl-benzyl)-7-piperazin-1-ylmethyl-6-trifluoromethyl-1H-quinazoline-2,4-dione (Compound F-1, 30.8 mg, 0.053 mmol) and DIPEA (10.2 mul, 0.059 mmol) in chloroform (0.265 ml), and the mixture was stirred at room temperature for 8.5 hours. DIPEA (8.33 mul, 0.048 mmol), <strong>[624-75-9]iodoacetonitrile</strong> (3.46 mul, 0.048 mmol), and chloroform (0.265 ml) were further added to this reaction solution, and the mixture was stirred at room temperature for 14.5 hours. Ethyl acetate (15 ml) and THF (15 ml) were added to the reaction mixture, and the organic layer was washed with a saturated aqueous ammonium chloride solution and brine, and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the residue obtained by concentration under reduced pressure was purified by amino silica gel column chromatography (MeOH/DCM) to give the title compound (29.3 mg, 89%) as a colorless amorphous. LCMS: m/z 618 [M+H]+ HPLC retention time: 1.77 min (analysis condition C)

Reference： [1]Patent: EP2842946,2015,A1 .Location in patent: Paragraph 0775; 0776

48
[ 603-76-9 ]
[ 624-75-9 ]
[ 70299-06-8 ]

Yield	Reaction Conditions	Operation in experiment
59%		General procedure: A 1.5 mL (1.5 mmol) ofPhBCl2 (1.0 mol/L in CH2Cl2) was added to CH2Cl2 solution(4 mL) of the nitrile (5a) (173 mg, 1.2 mmol) at room temperatureunder argon. The mixture was stirred for 15 min. Theindole (1a) (131 mg, 1.0 mmol) was added dropwise to this solutionat room temperature. The resulting solution was stirredfor 3 h, and then 0.5 mol/L Na2CO3 was added to quench thereaction. The resulting mixture was extracted with CH2Cl2.The organic layer was washed with saturated brine, dried(MgSO4), and evaporated. The crude product was purifiedusing silica gel chromatography to provide 3aa (226 mg, 82%yield).

Reference： [1]Chemical and Pharmaceutical Bulletin,2015,vol. 63,p. 538 - 545

49
[ 4010-81-5 ]
[ 624-75-9 ]
2-(2-chloro-6-morpholino-9H-purin-9-yl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate; In dimethyl sulfoxide; acetonitrile; at 60℃; for 3h;	Step 2: Synthesis of 2-(2-chloro-6-morpholino-9H-purin-9-yl)acetonitrile (14c)To a solution of 13a (1.18 g, 4.94 mmol) in acetonitrile/DMSO (19:1) was added 2- <strong>[624-75-9]iodoacetonitrile</strong> (0.71 mL, 9.87 mmol) and K2C03 (1.36 g, 9.87 mmol). The resulting mixture was heated at 60CC for 3 h. Then the solvents were removed in vacuo and water was added. The aqueous layer was extracted with DCM (x2) and the combined organic layers was washed with brine (xl), dried over MgSO4 and evaporated in vacuo. The crude oil was purified by flash chromatography(silica, 50% ethyl acetate in hexanes) to afford 14c (1.31 g, 95%) as pale brown solid.

Reference： [1]Patent: WO2015/137887,2015,A1 .Location in patent: Page/Page column 67
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 1552 - 1575

50
[ 624-75-9 ]
[ 15796-89-1 ]
[ 4148-26-9 ]

Yield	Reaction Conditions	Operation in experiment
44%	With rongalite; In water; N,N-dimethyl-formamide; at 80℃; for 6h;	General procedure: 1 (0.5mmol), 2 (1.0mmol), HOCH2SO2Na·2H2O (231mg, 1.5mmol) and a stir bar were added to 25mL tube and then DMF (3mL) and H2O (3mL) were added. The mixture was allowed to stir at 80C for 6h under air (monitored by TLC). The solution was then diluted by ethyl acetate (20mL) and washed by a solution of K2CO3 and water, then dried by anhydrous Na2SO4. The crude mixture was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=15:1-5:1) to give the product 3.

Reference： [1]Tetrahedron,2015,vol. 71,p. 8416 - 8423

51
[ 624-75-9 ]
[ 1192-37-6 ]
[ 13992-92-2 ]

Yield	Reaction Conditions	Operation in experiment
93%		General procedure: A solution of Et3B (0.5 mL, 1.0 M in EtOH, 0.5 mmol) was added over 2 h by syringe pump to a stirred mixture of the iodide 2, 4,or 5 (2.0 mmol) and olefin 1 (1 mmol) in EtOH-H2O (1:1, 10 mL) in the dark and open to air. After complete addition, the brown mixture was allowed to stir for 1 h at r.t. DBU (457 mg, 3 mmol) was added at 0 C, and the mixture was stirred at r.t. overnight. After addition of a sat. aq solution of NH4Cl (50 mL), the mixture was extracted with Et2O (20 and 10 mL), and the organic phases were washed with brine (10 mL). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by column chromatography.

Reference： [1]Synlett,2016,vol. 27,p. 745 - 748

52
4-sulfamylbutyryl-aminomethyl resin [ No CAS ]
[ 624-75-9 ]
[ 71989-31-6 ]
[ 35661-40-6 ]
[ 118904-37-3 ]
[ 71989-23-6 ]
[ 71989-38-3 ]
C₆₀H₈₃N₁₀O₁₁PolS [ No CAS ]

Reference： [1]Journal of Peptide Science,2016,p. 607 - 617

53
[ 624-75-9 ]
[ 503-20-8 ]

Yield	Reaction Conditions	Operation in experiment
95.7%	With calcium fluoride; In pentan-3-one; at 100℃; for 2.5h;	Add 0.95 Kg of <strong>[624-75-9]iodoacetonitrile</strong> and 500 g of anhydrous calcium fluoride to a 3-liter reaction flask at room temperature, add 600 ml of 3-pentanone, turn on the electric stirrer and start Heating, the temperature rose to 100 C, reaction 2.5h.2. After the above reaction, cool to 52 C, install the distillation unit, raise the temperature to 110 C, distillation, and the liquid bottle is cooled with dry ice until no liquid flows out. The product yield was 95.7% and the purity reached 96.6%.3. The above product was placed in a 500 ml single-necked flask and distilled at 120 C under normal pressure to collect 78-80 C fractions. The vial was cooled with an acetone bath to give a mixture of fluoroacetonitrile having a purity of 99.8%

Reference： [1]Patent: CN104230753,2016,B .Location in patent: Paragraph 0035-0038

54
[ 934-37-2 ]
[ 624-75-9 ]
[ 21797-94-4 ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 5391 - 5397

55
[ 624-75-9 ]
[ 103-67-3 ]
[ 14321-25-6 ]