Name: 4522-35-4|3-Iodo-1H-pyrazole|98%
Brand: Ambeed
SKU: A362440
Price: 5.0 USD
Availability: InStock
Rating: 95 (22 reviews)

1
[ 111505-88-5 ]
[ 4522-35-4 ]
[ 111506-00-4 ]

Reference： [1]Tetrahedron Letters,1987,vol. 28,p. 3179 - 3182

2
[ 141998-84-7 ]
[ 4522-35-4 ]

Reference： [1]Heterocycles,1992,vol. 33,p. 813 - 818

4
[ 4522-35-4 ]
[ 74-88-4 ]
[ 92525-10-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 0.25h;	Step 2: 3-iodo-l-methyl-lH-rhoyrazole.To a stirred solution of 3-iodo-leta-rhoyrazole (0.5 g, 2.6 mMol) in anhydrous DMF (5.0 mL) was added iodor°ethane (3.7 g, 25.8 mMol). The resulting solution was cooled to 00C, and NaH (0.11 g, 2.8 EPO <DP n="64"/>mMol, 60% dispersion in mineral oil) was added. The reaction mixture was allowed to warm to ambient temperature, and was stirred for 15 minutes. Water (20 mL) was added, and the resulting solution was extracted with EtOAc (1 x 30 mL). The organic layer was washed with water (2 x 30 mL), and brine (1 x 30 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated to afford the title compound. LRMS (ESI) calculated for C4H5IN2 [M+H]+, 208.9; found 209.0.

Reference： [1]Synthesis,2002,p. 1509 - 1512
[2]Patent: WO2007/35309,2007,A1 .Location in patent: Page/Page column 62-63

5
[ 1820-80-0 ]
[ 4522-35-4 ]

Yield	Reaction Conditions	Operation in experiment
		Example 4N-(4-[l-(l-methyl-lH-pyrazol-3-yl)-lH-indol-5-yl]oxy}rhoyrintauidin-2-yl)benzene-l,3-diamine (Compound 75)Scheme 4Step 1: 3-iodo-lH-pyrazole.To a stirred suspension of lH-pyrazol-3-amine (1.0 g, 12 mMol) in concentrated HCl (16 mL) was added a solution of sodium nitrite (1.7 g, 24 mMol) in water (3.0 mL) over 5 minutes at 00C. To the resulting orange reaction mixture was added a solution of KI (5.0 g, 30 mMol) in water (7.0 mL) over 10 minutes, resulting in nitrogen evolution. The reaction mixture was stirred for 5 minutes, upon which nitrogen evolution ceased. TetaF (25 mL) was added, followed by water (25 mL). The aqueous mixture was extracted with Et2O (3 x 30 mL) and the combined organic extracts were washed with Na2S2O3 (2 x 30 mL), dried over magnesium sulfate, filtered and concentrated to afford the title compound. LRMS (ESI) calculated for C3H3IN2 [M+HJ+, 194.9; found 194.9.
	With hydrogenchloride; potassium iodide; sodium nitrite; In water; at 0 - 28℃; for 2.75h;	To a stirred suspension of 118 (2.00g, 24.O7mmol) in concentrated HC1 (32mL) was added a solution ofNaNO2 (3.32g. 48.i4mmoi) in water (5mL) over 5 minutes at 0C. To the resulting orange reaction mixture was added a solution of KI (9.99g, 60 iSmmol) in water (l0mL) over 10 minutes. The reaction mixture was stirred at 0C for 30 minutes and then kept at 28C for another 2 hours, TLC showed the reaction was complete, then, solvent THF (3OmL) was added,followed by water (3OmL). The aqueous mixture was extracted with EtOAc (3 x8OmL) and the combined organic extracts were washed with Na2S2O3 (2 x4OmL), dried over Na2SO4, filtered and concentrated in vacuum to afford product 180 (200 g, crude), the crude product was used directly for the next step without purification.LCMS: m/z, i94.9M+H)??.

Reference： [1]Patent: WO2007/35309,2007,A1 .Location in patent: Page/Page column 62
[2]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 95

6
[ 402-44-8 ]
[ 4522-35-4 ]
[ 1164166-10-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h;	A mixture of <strong>[4522-35-4]3-iodopyrazole</strong> (prepared as described in WO2007/035309) (1.0 g, 5.1 mmol), 4-fluorobenzotrifluoride (0.72 mL, 5.7 mmol) and potassium carbonate (0.93g, 6.7 mmol) was stirred in lambda/,lambda/-dimethylformamide (10 mL) at 100 0C for 2 h. The mixture was diluted with water (60 mL) and extracted with ethyl acetate (2 x 30 mL). The organic layers were combined, dried over magnesium sulfate and concentrated. The residue after evaporation was subjected to silica gel chromatography (40 g silica) using a gradient of ethyl acetate/chlorobutane (0:100 to 50:50), and appropriate fractions were combined and evaporated to give the title compound (1.27 g). 1H NMR (CDCl3) delta 7.79 (m, 3H), 7.71 (m, 2H), 6.67 (d, IH).

Reference： [1]Patent: WO2009/86041,2009,A1 .Location in patent: Page/Page column 42

7
[ 446-33-3 ]
[ 4522-35-4 ]
3-iodo-1-(3-methyl-4-nitrophenyl)-1H-pyrazole [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 11628 - 11631
Angew. Chem.,2013,vol. 125,p. 11842 - 11845,4

8
[ 4522-35-4 ]
[ 882679-40-5 ]
[ 1533442-82-8 ]

Yield	Reaction Conditions	Operation in experiment
41%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 18h;Inert atmosphere;	Compound 51.1. Methyl 4-methyl-3-(lH-pyrazoI-5-yl)benzoate. To methyl 4- methyl-3-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)benzoate (compound 5.4, 800 mg, 2.9 mmol) in dioxane (30 mL) was added 5-iodo-lH-pyrazole (674 mg, 3.5 mmol), and Pd(dppf)Cl2 FontWeight="Bold" FontSize="10" DCM (237 mg, 0.29 mmol). The mixture was degassed with argon and stirred for 10 minutes then an aqueous potassium carbonate solution (2 M, 8 mL) was added. The mixture was heated at 90 C for 18 h, then cooled and diluted with EtOAc and filtered through Celite. The filtrate was washed with brine, dried (MgS04), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (Si02; 0-30 % EtOAc in hexanes) to yield 258 mg (41 %) of the title compound as a solid. m/z
41%		Compound 51.1. Methyl 4-methyl-3-(lH-pyrazol-5-yl)benzoate. To methyl 4- methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzoate (compound 5.4, 800 mg, 2.9 mmol) in dioxane (30 mL) was added 5-iodo-lH-pyrazole (674 mg, 3.5 mmol), and Pd(dppf)Cl2 DCM (237 mg, 0.29 mmol). The mixture was degassed with argon and stirred for 10 minutes then an aqueous potassium carbonate solution (2 M, 8 mL) was added. The mixture was heated at 90 C for 18 h, then cooled and diluted with EtOAc and filtered through Celite. The filtrate was washed with brine, dried (MgSC^), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (S1O2; (M0-30 % EtOAc in hexanes) to yield 258 mg (41 %) of the title compound as a solid, m/z (ES+) 217 (M-H)+

Reference： [1]Patent: WO2014/8197,2014,A1 .Location in patent: Page/Page column 120
[2]Patent: WO2015/95767,2015,A1 .Location in patent: Page/Page column 135; 136

9
[ 18997-19-8 ]
[ 4522-35-4 ]
[ 1616070-60-0 ]

Yield	Reaction Conditions	Operation in experiment
		3-Iodo-1H-pyrazole (19.44 g, 100 mmol) was charged to a flask followed byTHF (237 mL) and the solution was cooled to -10 C. NaH (4.41 g, 110 mmol)was added in portions keeping the internal temperature below -10 C. Thereaction was stirred for 30 min, then chloromethyl pivalate (17.45 mL, 120mmol) was added and the reaction was stirred for 1 h at -1 0 C and then allowedto warm to room temperature. The reaction was cooled in an ice bath andquenched with sat. NH4Cl then diluted with EtOAc and water. The organiclayer was washed with brine, dried over MgS04 and the solvent was removed.The product was purified by flash chromatography eluting with 0-50%EtOAc/hexane to give (3-iodo-1H-pyrazol-1-yl)methyl pivalate, as a white solid.LCMS calc.= 309.01; found= 308.87 (M+H+).
		3-Iodo-lH-pyrazole (19.44 g, 100 mmol) was charged to a flask followed by THF (237 mL) and the solution was cooled to -10 C. NaH (4.41 g, 110 mmol) was added in portions keeping the internal temperature below -10 C. The reaction was stirred for 30 min, then chloromethyl pivalate (17.45 mL, 120 mmol) was added and the reaction was stirred for 1 h at -10 C and then allowed to warm to room temperature. The reaction was cooled in an ice bath and quenched with sat. NH4C1 then diluted with EtOAc and water. The organic layer was washed with brine, dried over MgS04 and the solvent was removed. The product was purified by flash chromatography eluting with 0-50% EtOAc/hexane to give (3-iodo-lH-pyrazol-l-yl)methyl pivalate, as a white solid. LCMS calc. = 309.01 ; found = 308.87 (M+H+).
		Step A: (3-Iodo-lH-pyrazol-l -yl)methyl pivalate To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (1.40 g) in THF (25 mL) was added NaH (0.32 g, 60%wt) at 0 C. After stirring for 10 min at 0 C, chloromethyl pivalate (1.14 g) was added to the reaction at the same temperature. The reaction mixture was stirred for 1 h at room temperature. It was diluted with sat. NaHC03 aq. and extracted with EtOAc (2 times). The combined organic layer was washed with brine, dried over Na2S04, filtered and concentrated to give (3-iodo-lH-pyrazol-l -yl)methyl pivalate, as a brown oil, which was used in the next step without further purification. LCMS 331 (M+Na)+. NMR (300 MHz, CDC13): 5 7.48 (1 H, d, J= 2 Hz), 6.45 (1 H, d, J= 2 Hz), 5.97 (2 H, s), 1.17 (9 H, s).

Reference： [1]Patent: WO2014/99695,2014,A1 .Location in patent: Page/Page column 62
[2]Patent: WO2014/99694,2014,A1 .Location in patent: Page/Page column 107; 108
[3]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 98

10
[ 1220039-64-4 ]
[ 4522-35-4 ]
[ 1616069-42-1 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of<strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (0.75 g) in DMSO (19 mL), was added60% NaH (0.39 g) under ice cooling and stirred for 10 min. 4-bromopyridazinehydrobromide (1.4 g) was added and stirred at room temperature for 3 days.Then 60% NaH (0.16 g) was added at 0 OC and warmed to room temperatureand stirred for 1 day. The reaction mixture was diluted with water and EtOAc. The mixture was filtered with Celite, and extracted with EtOAc. The combinedorganic layer was washed with brine and dried with anhyd. Na2S04. It wasfiltered to remove insoluble matters and it was concentrated in vacuo. Theresidue was triturated (Hexane:EtOAc= 1:1) to obtain compound 2-1 as a brownsolid.

Reference： [1]Patent: WO2014/99695,2014,A1 .Location in patent: Page/Page column 37; 38

11
[ 96530-81-3 ]
[ 4522-35-4 ]
[ 1350475-30-7 ]

Yield	Reaction Conditions	Operation in experiment
		To <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (763 mg, 3.93 mmol) in DMSO (15 mL) at 0 oc, wasadded sodium hydride (60% in mineral oil, 189 mg, 4.72 mmol). The reactionwas warmed to 25 C and stirred for 60 min before 4-fluoro-2-methoxypyridine (500 mg, 3.93 mmol) was added. The reaction mixture was stirred at 90 C for4.5 h before quenching by the addition of water. The reaction mixture wasextracted with EtOAc. The combined organic extracts were dried over MgS04and concentrated in vacuo. The crude mixture was purified by flashchromatography (ISCO Combiflash, 0-30% EtOAc in hexanes) to afford 4-(3-iodo-1H-pyrazol-1-yl)-2-methoxypyridine, as a white solid. LCMS calc.=301.97; found= 302.02 (M+Ht
		To 3-iodo-lH-pyrazole (763 mg, 3.93 mmol) in DMSO (15 mL) at 0 C, was added sodium hydride (60% in mineral oil, 189 mg, 4.72 mmol). The reaction was warmed to 25 C and stirred for 60 min before 4-fluoro-2-methoxypyridine (500 mg, 3.93 mmol) was added. The reaction mixture was stirred at 90 C for 4.5 h before quenching by the addition of water. The reaction mixture was extracted with EtOAc. The combined organic extracts were dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 0-30% EtOAc in hexanes) to afford 4-(3- iodo-lH-pyrazol-l-yl)-2-methoxypyridine, as a white solid. LCMS calc. = 301.97; found = 302.02 (M+H)+.
		INTERMEDIATE 24 4-(3-Iodo-l H-pyrazol- 1 -yl)-2-methoxypyridine To 3-iodo-lH-pyrazole (763 mg, 3.93 mmol) in DMSO (15 mL) at 0 C, was added sodium hydride (60% in mineral oil, 189 mg, 4.72 mmol). The reaction was warmed to 25 C and stirred for 60 min before 4-fluoro-2-methoxypyridine (500 mg, 3.93 mmol) was added. The reaction mixture was stirred at 90 C for 4.5 h before quenching by the addition of water. The reaction mixture was extracted with EtOAc. The combined organic extracts were dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 0-30% EtOAc in hexanes) to afford 4-(3-iodo-17J-pyrazol-l-yl)-2-methoxypyridine, as a white solid. LCMS calc. = 301.97; found = 302.02 (M+H)+.

Reference： [1]Patent: WO2014/99695,2014,A1 .Location in patent: Page/Page column 44; 45
[2]Patent: WO2014/99694,2014,A1 .Location in patent: Page/Page column 86
[3]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 44-45

12
[ 850246-04-7 ]
[ 4522-35-4 ]
[ 1616069-32-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.70 g, 3.61 mmol), in DMSO (18.0 mL) wasadded sodium hydride (60% disp. in oil, 0.173 g, 4.33 mmol), and the resultingmixture was stirred for 0.5 h before adding 4-fluoro-2-trifluoromethyl pyridine(0.596 g, 3.61 mmol). The reaction mixture was stirred at 90 oc for 3 h. Thereaction was quenched by the addition of water and extracted with EtOAc. Thecombined organic extracts were washed with water and brine, dried overMgS04 and concentrated in vacuo. The crude mixture was purified by flashchromatography (ISCO, 40 g, 0-50 % EtOAc in hexanes) to afford 4-(3-iodo-1H-pyrazol-1-yl)-2-(trifluoromethyl)pyridine, as a white solid. LCMS calc. =339.95; found= 339.93 (M+H)+. 1H NMR (500 MHz, CDCh): o 8.77 (d, J=5.3 Hz, 1 H); 8.03 (d, J = 3.8 Hz, 1 H); 7.91 (d, J = 2.6 Hz, 1 H); 7.77 (d, J =5.4 Hz, 1 H); 6.74 (d, J= 2.5 Hz, 1 H).
		To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.70 g, 3.61 mmol), in DMSO (18.0 mL) was added sodium hydride (60% disp. in oil, 0.173 g, 4.33 mmol), and the resulting mixture was stirred for 0.5 h before adding 4-fluoro-2-trifluoromethyl pyridine (0.596 g, 3.61 mmol). The reaction mixture was stirred at 90 C for 3 h. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS0 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO, 40 g, 0-50 % EtOAc in hexanes) to afford 4-(3-iodo- lH-pyrazol-l-yl)-2-(trifluoromethyl)pyridine, as a white solid. LCMS calc. = 339.95; found = 339.93 (M+H)+. 1H NMR (500 MHz, CDC13): delta 8.77 (d, J= 5.3 Hz, 1 H); 8.03 (d, J- 3.8 Hz, 1 H); 7.91 (d, J= 2.6 Hz, 1 H); 7.77 (d, J= 5.4 Hz, 1 H); 6.74 (d, J = 2.5 Hz, 1 H).
		INTERMEDIATE 20 4-(3-Iodo- lH-pyrazol-1 -yl)-2-(trifluoromethyl)pyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.70 g, 3.61 mmol), in DMSO (18.0 mL) was added sodium hydride (60% disp. in oil, 0.173 g, 4.33 mmol), and the resulting mixture was stirred for 0.5 h before adding 4-fluoro-2-trifluoromethyl pyridine (0.596 g, 3.61 mmol). The reaction mixture was stirred at 90 C for 3 h. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO, 40 g, 0-50 % EtOAc in hexanes) to afford 4-(3-iodo-lH-pyrazol-l-yl)-2-(trifluoromethyl)pyridine, as a white solid. LCMS calc. = 339.95; found = 339.93 (Mu+Eta)+. NMR (500 MHz, CDC13): delta 8.77 (d, J= 5.3 Hz, 1 H); 8.03 (d, J= 3.8 Hz, 1 H); 7.91 (d, J= 2.6 Hz, 1 H); 7.77 (d, J= 5.4 Hz, 1 H); 6.74 (d, J= 2.5 Hz, 1 H).

Reference： [1]Patent: WO2014/99695,2014,A1 .Location in patent: Page/Page column 45
[2]Patent: WO2014/99694,2014,A1 .Location in patent: Page/Page column 86; 87
[3]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 42

13
4-iodopyridazine [ No CAS ]
[ 4522-35-4 ]
[ 1616069-42-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In dimethyl sulfoxide; at 0 - 50℃;	To the stirred solution of 4-iodopyridazine (1 000 mg, 4.85 mmol) and 3-iodolH-pyrazole (951 mg, 4.90 mmol) in DMSO was added NaH ( 60% in oil, 233mg, 5.83 mmol) in portion at 0 C. The mixture was stirred at room temparature for 30 min or until bubbling ceased, then warmed up to 50 C and stirred at50 C overnight. The reaction mixture was cooled to room temperature,partitioned between EtOAc and water. The aqueous was extracted with EtOAcfor three times. The organic phases were combined, dried over Na2S04 andconcentrated in vacuo to give the crude product. This was purified by flashchromatography (Isco CombiFlash, 80 g Silica gel column, 0-100% EtOAc inhexanes) to afford 4-(3-iodo-1H-pyrazol-1-yl)pyridazine. LCMS calc.= 272.96;found= 272.96 (M+Ht. 1H NMR (500 MHz, CDCl)): o 9.64 (d, J = 3.0 Hz, 1H); 9.27 (d, J = 6.0 Hz, 1 H); 7.95 (d, J = 2.5 Hz, 1 H); 7.81 (dd, J = 2.5 Hz, J= 5.5 Hz, 1 H); 6.79 (d, J = 2.5 Hz, 1 H).
	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 0 - 50℃;	To the stirred solution of 4-iodopyridazine (1000 mg, 4.85 mmol) and 3-iodo- lH-pyrazole (951 mg, 4.90 mmol) in DMSO was added NaH ( 60% in oil, 233 mg, 5.83 mmol) in portion at 0 C. The mixture was stirred at room temparature for 30 min or until bubbling ceased, then warmed up to 50 C and stirred at 50 C overnight. The reaction mixture was cooled to room temperature, partitioned between EtOAc and water. The aqueous was extracted with EtOAc for three times. The organic phases were combined, dried over Na S04 and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Isco CombiFlash, 80 g Silica gel column, 0-100% EtOAc in hexanes) to afford 4-(3-iodo-lH-pyrazol-l -yl)pyridazine. LCMS calc. = 272.96; found = 272.96 (M+H)+. 1H NMR (500 MHz, CDC13): delta 9.64 (d, J = 3.0 Hz, 1 H); 9.27 (d, J = 6.0 Hz, 1 H); 7.95 (d, J = 2.5 Hz, 1 H); 7.81 (dd, J = 2.5 Hz, J = 5.5 Hz, 1 H); 6.79 (d, J = 2.5 Hz, 1 H).
	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 0 - 50℃;	INTERMEDIATE 39 4-(3 -Iodo- 1 H-p yrazol- 1 -yl)pyridazine To the stirred solution of 4-iodopyridazine (1000 mg, 4.85 mmol) and 3-iodo-lH- pyrazole (951 mg, 4.90 mmol) in DMSO was added NaH ( 60% in oil, 233 mg, 5.83 mmol) in portion at 0 C. The mixture was stirred at room temparature for 30 min or until bubbling ceased, then wanned up to 50 C and stirred at 50 C overnight. The reaction mixture was cooled to room temperature, partitioned between EtOAc and water. The aqueous was extracted with EtOAc for three times. The organic phases were combined, dried over Na2S04 and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Isco CombiFlash, 80 g Silica gel column, 0-100% EtOAc in hexanes) to afford 4-(3-iodo-lH-pyrazol-l- yl)pyridazine. LCMS calc. = 272.96; found = 272.96 (M+H)+. NMR (500 MHz, CDC13): delta 9.64 (d, J = 3.0 Hz, 1 H); 9.27 (d, J = 6.0 Hz, 1 H); 7.95 (d, J = 2.5 Hz, 1 H); 7.81 (dd, J = 2.5 Hz, J = 5.5 Hz, 1 H); 6.79 (d, J = 2.5 Hz, 1 H).

Reference： [1]Patent: WO2014/99695,2014,A1 .Location in patent: Page/Page column 45; 46
[2]Patent: WO2014/99694,2014,A1 .Location in patent: Page/Page column 87
[3]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 53-54

14
[ 4522-35-4 ]
[ 1837-55-4 ]
[ 1616070-35-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In N,N-dimethyl-formamide; at 100℃; for 1h;	To a soluton of<strong>[4522-35-4]3-iodopyrazole</strong> (500 mg, 2.58mmol) and 3,5-dichloropyridazine(384 mg, 2.58 mmol) in anhydrous DMF (5 mL) at room temperature was addedpotassium tert-butoxide (289 mg, 2.58 mmol) in one portion. It was heated at100 C for 1 h. It was cooled to room temperature, diluted with EtOAc (50 mL),washed with satd aq. NaHC03 (10 mL) and water (100 mL). The aqueous layerwas separated and extracted with EtOAc (3 x 50 mL). The combined organiclayers were washed with water (1 00 mL), brine (1 00 mL), dried over Na2S04,filtered and concentrated. The residue was purified by flash chromatography(ISCO Combiflash, Gold 40 g, 0-60% EtOAc in hexanes) to give 3-chloro-5-(3-iodo-1H-pyrazol-1-yl)pyridazine, as a white solid. LCMS calc.= 306.92, found= 306.96 (M+Ht. 1H NMR (500 MHz, CHCh-d): o 9.54 (d, J= 2.3 Hz, 1 H);7.94 (d, J= 2.7 Hz, 1 H); 7.90 (d, J= 2.3 Hz, 1 H); 6.81 (d, J= 2.7 Hz, 1 H).
	With potassium tert-butylate; In N,N-dimethyl-formamide; at 100℃; for 1h;	3-Chloro-5-(3-iodo-lH-pyrazol-l -vDpyridazine To a soluton of <strong>[4522-35-4]3-iodopyrazole</strong> (500 mg, 2.58 mmol) and 3,5-dichloropyridazine (384 mg, 2.58 mmol) in anhydrous DMF (5 mL) at room temperature was added potassium teri-butoxide (289 mg, 2.58 mmol) in one portion. It was heated at 100 C for 1 h. It was cooled to room temperature, diluted with EtOAc (50 mL), washed with satd aq. NaHC03 (10 mL) and water (100 mL). The aqueous layer was separated and extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried over Na2S04, filtered and concentrated. The residue was purified by flash chromatography (ISCO Combiflash, Gold 40 g, 0-60% EtOAc in hexanes) to give 3-chloro-5-(3- iodo-lH-pyrazol-l-yl)pyridazine, as a white solid. LCMS calc. = 306.92, found = 306.96 (M+H)+. NMR (500 MHz, CHCl3-d): delta 9.54 (d, J= 2.3 Hz, 1 H); 7.94 (d, J= 2.7 Hz, 1 H); 7.90 (d, J= 2.3 Hz, 1 H); 6.81 (d, J= 2.7 Hz, 1 H).
	With potassium tert-butylate; In N,N-dimethyl-formamide; at 100℃; for 1h;	INTERMEDIATE 40 3-Chloro-5-(3-iodo-lH-pyrazol-l-yl pyridazine To a soluton of <strong>[4522-35-4]3-iodopyrazole</strong> (500 mg, 2.58 mmol) and 3,5-dichloropyridazine (384 mg, 2.58 mmol) in anhydrous DMF (5 mL) at room temperature was added potassium tert-butoxide (289 mg, 2.58 mmol) in one portion. It was heated at 100 C for 1 h. It was cooled to room temperature, diluted with EtOAc (50 mL), washed with satd aq. NaHC03 (10 mL) and water (100 mL). The aqueous layer was seperated and extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried over Na2S04, filtered and concentrated. The residue was purified by flash chromatography (ISCO Combiflash, Gold 40 g, 0-60% EtOAc in hexanes) to give 3-chloro-5-(3-iodo-lH-pyrazol-l-yl)pyridazine, as a white solid. LCMS calc. = 306.92, found = 306.96 (M+H)+. NMR (500 MHz, CHC13- d): 5 9.54 (d, J= 2.3 Hz, 1 H); 7.94 (d, J= 2.7 Hz, 1 H); 7.90 (d, J= 2.3 Hz, 1 H); 6.81 (d, J= 2.7 Hz, 1 H).

Reference： [1]Patent: WO2014/99695,2014,A1 .Location in patent: Page/Page column 46
[2]Patent: WO2014/99694,2014,A1 .Location in patent: Page/Page column 87; 88
[3]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 54

15
[ 1616070-39-3 ]
[ 4522-35-4 ]
[ 1616070-37-1 ]

Yield	Reaction Conditions	Operation in experiment
		To <strong>[4522-35-4]3-iodopyrazole</strong> (124 mg, 0.641 mmol) in DMF (2 mL)was added potassiumtert-butoxide (53 mg, 0.472 mmol) at 0 C. The mixture was stirred at roomtemperature for 15 min. It was transfered into a solution of 5- chloro-3-(trifluoromethyl)pyridazine (78 mg, 0.427 mmol) in DMF (2 mL) at 0 C. Itwas warmed to room temperature, stirring for 30 min. It was diluted withEt0Ac(20 mL), washed with water (3 x 20 niL), the combined aqueous layerswere extracted with EtOAc (30 mL), the combined organic layers were washedwith brine (30 mL), dried over Na2S04, filtered and concentrated. The residuewas purified by flash chromatography (ISCO Combiflash, 12 g, 0-1 00% EtOAcin hexanes) to give a mixture of<strong>[4522-35-4]3-iodopyrazole</strong> and the desired product (1 :2,180 mg). It was disolved in anhydrous CH2Cb (2 mL) and added a little bit ofDMAP and of di-tert-butyl dicarbonate (~ 100 mg). It was stirred at roomtemperature for 10 min and purified by flash chromatography (IS COCombiflash, 0-40% EtOAc in hexanes) to give 5-(3-iodo-1H-pyrazol-1-yl)-3-(trifluoromethyl)pyridazine, as white solid. LCMS calc. = 340.95, found =340.84 (M+H/. 1H NMR (500 MHz, CHCb-d): 6 9.78 (d, J= 2.5 Hz, 1 H);8.17(d,J=2.5Hz, 1 H); 8.04(d,J=2.7Hz, 1 H); 6.84(d,J=2.7Hz, 1 H).
		To <strong>[4522-35-4]3-iodopyrazole</strong> (124 mg, 0.641 mmol) in DMF (2 mL)was added potassium teri-butoxide (53 mg, 0.472 mmol) at 0 C. The mixture was stirred at room temperature for 15 min. It was transferee into a solution of 5- chloro-3- (trifluoromethyl)pyridazine (78 mg, 0.427 mmol) in DMF (2 mL) at 0 C. It was warmed to room temperature, stirring for 30 min. It was diluted with EtOAc(20 mL), washed with water (3 x 20 mL), the combined aqueous layers were extracted with EtOAc (30 mL), the combined organic layers were washed with brine (30 mL), dried over Na2S04, filtered and concentrated. The residue was purified by flash chromatography (ISCO Combiflash, 12 g, 0-100% EtOAc in hexanes) to give a mixture of <strong>[4522-35-4]3-iodopyrazole</strong> and the desired product (1 :2, 180 mg). It was disolved in anhydrous CH2C12 (2 mL) and added a little bit of DMAP and of di-teri-butyl dicarbonate (~ 100 mg). It was stirred at room temperature for 10 min and purified by flash chromatography (ISCO Combiflash, 0-40%> EtOAc in hexanes) to give 5-(3-iodo-lH-pyrazol-l-yl)-3- (trifluoromethyl)pyridazine, as a white solid. LCMS calc. = 340.95, found = 340.84 (M+H)+. NMR (500 MHz, CHCl3-d): delta 9.78 (d, J= 2.5 Hz, 1 H); 8.17 (d, J= 2.5 Hz, 1 H); 8.04 (d, J= 2.7 Hz, 1 H); 6.84 (d, J= 2.7 Hz, 1 H).
		Step C: 5-(3-Iodo-lH-pyrazol-l -yl)-3-(trifluoiOmethyl)pyridazine To <strong>[4522-35-4]3-iodopyrazole</strong> (124 mg, 0.641 mmol) in DMF (2 mL)was added potassium tert- butoxide (53 mg, 0.472 mmol) at 0 C. The mixture was stirred at room temperature for 15 min. It was transfered into a solution of 5- chloro-3- (trifluoromethyl)pyridazine (78 mg, 0.427 mmol) in DMF (2 mL) at 0 C. It was wanned to room temperature, stirring for 30 min. It was diluted with EtOAc(20 mL), washed with water (3 x 20 mL), the combined aqueous layers were extracted with EtOAc (30 mL), the combined organic layers were washed with brine (30 mL), dried over Na2S04, filtered and concentrated. The residue was purified by flash chromatography (ISCO Combiflash, 12 g, 0-100% EtOAc in hexanes) to give a mixture of <strong>[4522-35-4]3-iodopyrazole</strong> and the desired product (1 :2, 180 mg). It was disolved in anhydrous CH2C12 (2 mL) and added a little bit of DMAP and of di-fert-butyl dicarbonate (~ 100 mg). It was stirred at room temperature for 10 min and purified by flash chromatography (ISCO Combiflash, 0-40% EtOAc in hexanes) to give 5 -(3- iodo-lH-pyrazol-l-yl)-3-(trifluoromethyl)pyridazine, as white solid. LCMS calc. = 340.95, found = 340.84 (M+H)+. NMR (500 MHz, CHCl3-d): delta 9.78 (d, J= 2.5 Hz, 1 H); 8.17 (d, J= 2.5 Hz, 1 H); 8.04 (d, J= 2.7 Hz, 1 H); 6.84 (d, J = 2.7 Hz, 1 H).

Reference： [1]Patent: WO2014/99695,2014,A1 .Location in patent: Page/Page column 48; 49
[2]Patent: WO2014/99694,2014,A1 .Location in patent: Page/Page column 89; 90
[3]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 57-58

16
[ 694-52-0 ]
[ 4522-35-4 ]
4-(3-iodo-1H-pyrazol-1-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (7.26 g) in DMSO (200 mL) was added NaH (1.80 g, 60%wt) at 0 C, and it was stirred for 15 min. To the reaction mixture was added mixture of 4-fluoropyridine (5.00 g) and NaH (1.80 g) in DMSO (175 mL) at room temperature. It was stirred for 2 h at 90 C. The reaction mixture was cooled to room temperature, and it was diluted with EtOAc and H20. The mixture was extracted with EtOAc (2 times), and the combined organic layer were washed with H20 and brine and dried over Na2S04. It was filtered to remove insoluble matters and it was concentrated in vacuo. The residue was triturated with EtOAc to give compound 1-5 as a pale brown solid.

Reference： [1]Patent: WO2014/99694,2014,A1 .Location in patent: Page/Page column 38

17
[ 4522-35-4 ]
[ 475275-69-5 ]
[ 1621525-22-1 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; copper diacetate; caesium carbonate; In 1,4-dioxane; at 80℃;	INTERMEDIATE 29 5-Chloro-4-(3-iodo-lH-pyrazol-l-yl)-2-methoxypyridine A solution of 3-iodo-lH-pyrazole (0.3 g, 1.547 mmol), 5-chloro-2-methoxypyridine- 4-boronic acid (0.377 g, 2.011 mmol), DMAP (0.756 g, 6.19 mmol), copper(II)acetate (0.281 g, 1.547 mmol), and cesium carbonate (1.26 g, 3.87 mmol) in 1,4-dioxane (7.73 mL) was heated at 80 C overnight. The reaction was allowed to warm to room temperature and filtered. The filtrate was diluted with EtOAc and water, and the seperated aq. layer was extracted with EtOAc. The combined organics were dried over MgS04, filtered and concentrated. The residue was purified with flash chromatography (ISCO Combiflash, 24 g, 0-10 % EtOAc in hexanes) to give 5- chloro-4-(3-iodo-lH-pyrazol-l-yl)-2-methoxypyridine, as a white solid. LCMS calc. = 335.93; found = 335.82 (M+H)+. 1H NMR (500 MHz, CDC13): delta 8.25 (s, 1 H); 8.01 (d, J= 2.6 Hz, 1 H); 7.14 (s, 1 H); 6.66 (d, J= 2.5 Hz, 1 H); 3.96 (s, 3 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 48

18
[ 67815-54-7 ]
[ 4522-35-4 ]
[ 1621525-20-9 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 27 3 ,5 -Difluoro-4-(3 -iodo- 1 H-pyrazol- 1 -vDpyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.70 g, 3.61 mmol), in DMSO (15.1 mL) was added sodium hydride (60% in oil, 0.159 g, 3.97 mmol) and stirred for 0.5 h before 3,4,5- trifluoropyridine (0.48 g, 3.61 mmol) was added. The reaction mixture was stirred at 90 C for 3 h. This was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 40 g, 0-30 % EtOAc in hexanes) to give 3,5-difluoro-4-(3-iodo- lH-pyrazol-l-yl)pyridine, as a white solid. LCMS calc. = 307.94; found = 307.92 (M+H)+. 1H NMR (500 MHz, CDC13): delta 8.53 (s, 2 H); 7.65 (dd, J= 3.9, 2.3 Hz, 1 H); 6.72 (d, J= 2.5 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 47

19
[ 884495-00-5 ]
[ 4522-35-4 ]
[ 1621525-21-0 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 28 5-Fluoro-4-(3-iodo-lH-pyrazol-l-yl)-2-methoxypyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.20 g, 1.031 mmol), in DMSO (5.20 mL) was added sodium hydride (60% in oil, 0.045 g, 1.134 mmol) and stirred for 0.5 h before 4- bromo-5-fluoro-2-methoxypyridine (0.212 g, 1.031 mmol) was added. The reaction mixture was stirred at 80 C for 4 h. This was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 12 g, 0-20 % EtOAc in hexanes) to give 5- fluoro-4-(3-iodo-lH-pyrazol-l-yl)-2-methoxypyridine, as a white solid. LCMS calc. = 319.96; found = 320.05 (M+H)+. NMR (500 MHz, CDC13): delta 8.13 (d, J= 2.8 Hz, 1 H); 7.97 (d, J = 1.7 Hz, 1 H); 7.37 (m, 1 H); 6.67 (d, J= 2.6 Hz, 1 H); 3.94 (t, J = 1.2 Hz, 3 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 47-48

20
[ 1227577-09-4 ]
[ 4522-35-4 ]
[ 1621525-23-2 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 30 4- (3-Iodo-lH-pyrazol-l-yl)-2-methoxy-5-(trifluoromethyl)pyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.30 g, 1.547 mmol), in DMSO (7.73 mL) was added sodium hydride (60% in oil, 0.068 g, 1.701 mmol) and stirred for 0.5 h before 4-iodo- 5- trifluoromethyl-2-methoxypyridine (0.469 g, 1.547 mmol) was added. The reaction mixture was stirred at 80 C for 4 h. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 24 g, 0-20 % EtOAc in hexanes) to give 4-(3-iodo-lH-pyrazol-l-yl)-2-methoxy-5-(trifluoromethyl)pyridine, as a white solid. LCMS calc. = 369.96; found = 369.83 (M+H)+. NMR (500 MHz, CDC13): delta 8.58 (s, 1 H); 7.63 (s, 1 H); 7.01 (d, J ^ 2.8 Hz, 1 H); 6.65 (d, J= 2.6 Hz, 1 H); 4.03(d, J= 3.3 Hz, 3 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 48-49

21
[ 1621525-35-6 ]
[ 4522-35-4 ]
[ 1621525-34-5 ]

Yield	Reaction Conditions	Operation in experiment
		Step B: 5-(3-Iodo-lH-pyrazol-l-yl)-3-isopropoxypyridazine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (270 mg, 1.390 mmol) in anhydrous DMF (2 mL) at 0 C was added potassium iert-butoxide (143 mg, 1.275 mmol). It was stirred at room temperature for 10 min, and then 5-chloro-3-isopropoxypyridazine (200 mg, 1.159 mmol) was added neat. The mixture was stirred at room temperature for 15 min. It was heated at 100 C for 1 h. It was cooled to room temperature, diluted with EtOAc (20 mL), washed with water (3x20 mL). The combined aqueous layers were extracted with EtOAc (30 mL), washed with brine (20 mL), dried over Na2S04, filtered and concentrated. The residue was purified by flash chromatography (ISCO Combiflash, 12 g, 0-50% EtOAc in hexanes) to give the titled product, as a white solid. LCMS calc. = 331.01 ; found = 330.88 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 58-59

22
[ 1621525-39-0 ]
[ 4522-35-4 ]
[ 1621525-38-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In N,N-dimethyl-formamide; at 100℃; for 1h;	Step B: 3-(ter?-Butoxy)-5-(3-iodo-lH-pyrazol-l-yl)pyridazine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.208 g, 1.072 mmol) in DMF (5.36 mL) was added potassium teri-butoxide (0.132 g, 1.179 mmol) and then stirred at room temperature for 10 min. 3-(t<?r/-Butoxy)-5-chloropyridazine (0.2 g, 1.072 mmol) was added, then stirred at 100 C for 1 h, and cooled to room temperature. EtOAc and water were added and the organic was washed with water and brine, dried over MgS04, filtered and concentrated. The residue was purified by flash chromatography (ISCO Combiflash, 24 g, 0-30% EtOAc in hexanes) to give 3-(tert-Butoxy)-5-(3-iodo-lH- pyrazol-l-yl)pyridazine, as a white solid. LCMS calc. = 288.95; found = 288.87 (M+H-tert-Bu)+. NMR (500 MHz, CDC13): delta 9.22 (d, J= 2.2 Hz? 1 H); 7.83 (d, J= 2.5 Hz, 1 H); 7.09 (d, J= 2.3 Hz, 1 H); 6.70 (d, J= 2.5 Hz, 1 H); 1.69 (s, 9 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 60-61

23
[ 4522-35-4 ]
[ 14628-34-3 ]
[ 1621525-40-3 ]

Yield	Reaction Conditions	Operation in experiment
		Step B: 5-(3-Iodo-lH-pyrazol-l-yl)-2-methylpyridazin-3(2 /)-one To a clean dry flask was added sodium hydride (200 mg, 5.00 mmol) and anhydrous NMP (10 mL). The mixture was cooled to 0 C. 3-Iodopyrazole (959 mg, 4.95 mmol) was added to the mixture in one portion. The mixture was stirred for 10 min at room temperature, then 5-chloro-2-methylpyridazin-3(2H)-one (650 mg, 4.50 mmol) was added in one portion. The mixture was stirred at 100 C for 2 h. The reaction mixture was cooled to room temperature, water (100 mL) was added, and the resulting mixture was extracted with EtOAc (100 mL). The organic layer was washed with water (3 x 50 mL) and the combined aqueous layers were extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (ISCO Combiflash, 40 g, 0-100% EtOAc in hexanes) to give 5-(3-iodo-lH-pyrazol-l-yl)-2-methylpyridazin-3(2H)-one, as a white solid. LCMS calc. = 302.97; found = 302.95 (Mu+Eta)+. NMR (500 MHz, CDC13): delta 8.47 (d, J = 2.6 Hz, 1 H); 7.79-7.74 (d, J = 2.6 Hz, 1 H); 6.93 (d, J = 2.6 Hz, 1 H); 6.74 (d, J = 2.6 Hz, 1 H); 3.84 (s, 3 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 61-62

24
4-chloropyrimidine-2-carbonitrile [ No CAS ]
[ 4522-35-4 ]
[ 1621525-49-2 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 58 4-(3-Iodo-lH-pyrazol-l-yl)pyrimidine-2-carbonitrile To a solution of 3-iodo-lH-pyrazole (298 mg, 1.536 mmol) in anhydrous DMSO (4 mL) added NaH (86 mg, 2.151 mmol) at 0 C. The mixture was stirred for 30 min at 0C, followed by the addition of 4-chloropyrimidine-2-carbonitrile (214 mg, 1.536 mmol) in DMSO(l mL). The resulting mixture was stirred at room temperature overnight. The mixture was quenched with water (10 mL) and extracted with EtOAc(40 mL x 3). The organic layer was collected and dried over Na2S04. The solvent was removed in vacuo to give the crude product. This was purified by flash chromatography (IS CO Combiflash, lOg, Biotage Si column, -30 mL/min, 100% hexanes 5min, gradient to 100% EtOAc in hexanes 15min) to afford 4-(3-iodo-lH- pyrazol-l-yl)pyrimidine-2-carbonitrile. LCMS calc. = 297.95; found = 297.92 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 67

25
[ 4522-35-4 ]
[ 628692-15-9 ]
[ 1621525-47-0 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; copper diacetate; caesium carbonate; In 1,4-dioxane; at 80℃;	INTERMEDIATE 56 5-(3-Iodo-lH-pyrazol-l-yl)-2-methoxypyrimidine A solution of 3-iodo-lH-pyrazole (0.7 g, 3.61 mmol), 2-methoxypyrimidine -4- boronic acid (0.722 g, 4.69 mmol), DMAP (1.763 g, 14.43 mmol), copper(II) acetate (0.655 g, 3.61 mmol), and cesium carbonate (2.94 g, 9.02 mmol) in 1,4-dioxane (18.0 mL) was heated at 80 °C overnight. The reaction was allowed to room temperature and filtered. The filtrate was diluted with EtOAc and water, and the seperated aq. layer was extracted with EtOAc. The combined organics were dried over MgS04, filtered and concentrated. The residue was purified with flash chromatography (ISCO Combiflash, 40 g, 0-70percent EtOAc in hexanes) to give 5-(3-iodo-lH-pyrazol-l-yl)-2- methoxypyrimidine, as a white solid. LCMS calc. = 302.97; found = 302.86 (M+H)+. lR NMR (500 MHz, CDC13): delta 8.82 (s, 2 H); 7.66 (d, J= 2.6 Hz, 1 H); 6.68 (d, J= 2.5 Hz, 1 H); 4.07 (s, 3 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 66

26
[ 1308298-23-8 ]
[ 4522-35-4 ]
[ 1621525-48-1 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; copper diacetate; caesium carbonate; In 1,4-dioxane; at 80℃;	INTERMEDIATE 57 5-(3-Iodo-lH-pyrazol-l-yl)-2-(trifluorometyl)pyrimidine A solution of 3-iodo-lH-pyrazole (0.7 g, 3.61 mmol), 2-trifluoromethylpyrimidine -4- boronic acid (0.722 g, 4.69 mmol), DMAP (1.763 g, 14.43 mmol), copper(II) acetate (0.655 g, 3.61 mmol), and cesium carbonate (2.94 g, 9.02 mmol) in 1 ,4-dioxane (18.0 mL) was heated at 80 °C overnight. The reaction was allowed to room temperature and filtered. The filtrate was diluted with EtOAc and water, and the seperated aq. layer was extracted with EtOAc. The combined organics were dried over MgS04, filtered and concentrated. The residue was purified with flash chromatography (ISCO Combiflash, 40 g, 0-5 percent EtOAc in hexanes) to give 5-(3-iodo-lH-pyrazol-l-yl)-2- (trifluorometyl)pyrimidine, as a white solid. LCMS calc. = 340.94; found = 340.88 (M+H)+. NMR (500 MHz, CDC13): 8 9.25 (s, 2 H); 7.86 (d, J= 2.5 Hz, 1 H); 6.78 (d, J= 2.7 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 66-67

27
[ 4994-86-9 ]
[ 4522-35-4 ]
[ 1621525-50-5 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 59 4-(3-Iodo-lH-pyrazol-l -yl)-2-methylpyrimidine To a solution of 3-iodo-lH-pyrazole (500 mg, 2.58 mmol) in anhydrous DMSO (6 mL) was added NaH (155 mg, 3.87 mmol) at 0 C. The mixture was stirred for 30 min at 0 C, followed by the addition of 4-chloro-2-methylpyrimidine (331 mg, 2.58 mmol) in DMSO (2 mL). The resulting mixture was stirred at 90 C overnight. The mixture was cooled to room temperature, quenched with water (10 mL) and extracted EtOAc (40 mL x 3). The organic layer was collected and dried over Na2S04. The solvent was removed in vacuo to give the crude product. This was purified by flash chromatography (ISCO Combiflash, 24 g, Biotage Si column, -60 mL/min, 100% hexanes 5 min, gradient to 100% EtOAc in hexanes 15 min) to afford 4-(3-iodo-17J- pyrazol-l-yl)-2-methylpyrimidine. LCMS calc. = 286.98; found = 286.95 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 67-68

28
[ 959240-72-3 ]
[ 4522-35-4 ]
[ 1621525-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 0 - 90℃; for 4.5h;	INTERMEDIATE 60 4-(3-Iodo-lH-pyrazol-l-yl)-2-methoxypyrimidine To the stirred solution of 4-bromo-2-methoxypyrimidine (500mg, 2.65 mmol) and 3- iodo-lH-pyrazole (518 mg, 2.67 mmol) in DMSO was added NaH ( 60%> in oil, 132mg, 3.31 mmol) in portion at 0 C. The mixture was stirred at room temparature for 30 min or until bubbling ceased, then warmed up to 90 C and stirred at 90 C for 4 h. The reaction mixture was cooled to room temperature, partitioned between EtOAc and water. The aqueous was extracted with EtOAc for three times. The organic phases were combined, dried over Na2S04 and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Isco CombiFlash, 80 g Silica gel column, 0-50% EtOAc in hexanes) to afford 4-(3-iodo-lH-pyrazol-l-yl)- 2-methoxypyrimidine. LCMS calc. = 302.97; found = 302.99 (M+H)+. 1H NMR (500 MHz, CDC13): delta 8.58 (d, J = 1.5 Hz, 1 H); 8.42 (d, J = 2.0 Hz, 1 H); 7.57 (d, J = 1.5 Hz, 1 H); 6.67 (d, J = 2.0 Hz, 1 H); 4.08 (s, 3 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 68

29
[ 959240-54-1 ]
[ 4522-35-4 ]
[ 1621525-52-7 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 61 4-(3-Iodo-lH-pyrazol-l-yl)-N,N-dimethylpyrimidin-2-amine NaH (119 mg, 60% in oil, 2.97 mmol) was added to a solution of 3-iodo-lH-pyrazole (480 mg, 2.48 mmol) in anhydrous DMF (10 mL) at 25 C under N2. The mixture was stirred for 10 min and 4-bromo-N,N-dimethylpyrimidin-2-amine (500 mg, 2.48 mmol) was added. The resulting mixture was stirred for another 2 h at 25 C under N2. The reaction mixture was then quenched with saturated aq. NH4C1 solution and extracted with with EtOAc. The organic layer was washed with brine, dried (Na2S04) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Isco Combiflash Rf, RediSep Silica 40 g, 30% EtOAc in hexanes, then 30-100% EtOAc in hexanes) to afford 4-(3-iodo-lH-pyrazol-l-yl)-N,N- dimethylpyrimidin-2-amine. LCMS calc. = 314.99; found = 315.99 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 68-69

30
[ 455-15-2 ]
[ 4522-35-4 ]
[ 1621525-01-6 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 6 3-Iodo-l-(4-(methylsulfonyl)phenyl)-lH-pyrazole To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.7 g, 3.61 mmol) in DMSO (18.0 mL) was added sodium hydride (60% disp. in oil, 0.173 g, 4.33 mmol) and the resulting mixture was stirred for 0.5 h before adding 4-methylsulfoylfluorobenzene (0.629 g, 3.61 mmol). The reaction mixture was stirred at 90 C for 3 h. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flas chromatography (ISCO, 40 g, 0-60 % EtOAc in hexanes) to afford 3-iodo-l-(4-(methylsulfonyl)phenyl)-lH-pyrazole, as a white solid. LCMS calc. = 348.94; found = 348.92 (M+H)+. 1H NMR (500 MHz, CDC13): delta 8.03 (dd, J= 8.7, 1.7 Hz, 2 H); 7.89 (dd, J= 8.7, 1.7 Hz, 2 H); 7.84 (d, J= 2.6 Hz, 1 H); 6.69 (d, J= 2.6 Hz, 1 H); 3.09 (s, 3 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 35

31
[ 403-33-8 ]
[ 4522-35-4 ]
[ 1621525-02-7 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 7 Methyl 4-(3 -iodo- 1 H-p yrazol- 1 -yPbenzoate To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.7 g, 3.61 mmol) in DMSO (18.0 mL) was added sodium hydride (60% disp. in oil (0.173 g, 4.33 mmol), and the resulting mixture was stirred for 0.5 h before adding methyl 4- fluoro benzoate (0.556 g, 3.61 mmol). The reaction mixture was stirred at 90 C overnight. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO, 40 g, 0-20 % EtOAc in hexanes) to afford methyl 4-(3-iodo-lH-pyrazol-l-yl)benzoate, as a white solid. LCMS calc. - 328.97; found = 328.96 (M+H)+. NMR (500 MHz, CDC13): delta 8.12 (m, 2 H); 7.81 (d, J= 2.4 Hz, 1 H); 7.76 (m, 2 H); 6.65 (m, 1 H); 3.94 (s, 3 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 35-36

32
[ 4522-35-4 ]
[ 147754-12-9 ]
[ 1616069-58-9 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 8 4-(3 -Iodo- lH-p yrazol- 1 - vPbenzonitrile To 3-iodo-lH-pyrazole (801 mg, 4.13 mmol) in DMSO (10 mL) at 0 °C, was added sodium hydride (60percent in mineral oil, 198 mg, 4.95 mmol). The reaction was warmed to 25 °C and stirred for 60 min before methyl 4-fluorobenzonitrile (500 mg, 4.13 mmol) was added. The reaction mixture was stirred at 90 °C for 4.5 h before quenching by the addition of water. The reaction mixture was extracted with EtOAc. The combined organic extracts were dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combifiash, 0-30percent EtOAc in hexanes) to afford 4-(3-iodo-lH-pyrazol-l-yl)benzonitrile, as a pale yellow crystaline solid. LCMS calc. = 295.96; found = 295.90 (M+H)+. NMR (500 MHz, CDC13): delta 7.83 (m, 3 H); 7.78 (d, J= 8.5 Hz, 2 H), 6.71 (d, J= 2.6 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 36

33
[ 1765-93-1 ]
[ 4522-35-4 ]
[ 1621525-03-8 ]

Yield	Reaction Conditions	Operation in experiment
	With di-mu-hydroxo-bis[(N,N,N?,N?-tetramethylethylene-diamine)copper(II)] chloride; oxygen; In dichloromethane; at 25℃;Sealed tube;	INTERMEDIATE 10 1 -(4-Fluorophenyl)-3 -iodo- 1 H-pyrazole A mixture of 3-iodo-lH-pyrazole (1 g, 5.16 mmol), (4-fluorophenyl)boronic acid (0.866 g, 6.19 mmol) and [Cu(Cl) (OH)(Me2NCH2CH2NMe2)]2 (0.479 g, 1.031 mmol) in CH2C12 (20.6 mL) was sealed and stirred at 25 C under an atmosphere of oxygen (balloon) overnight. The reaction was filtered over Celite to remove insoluble solids and the filter was washed well with CH2C12. The filtrate was concentrated in vacuo and purified by flash chromatography (ISCO Combiflash, 40 g silica gel column, 0- 10% EtOAc in hexanes) to afford l-(4-fluorophenyl)-3 -iodo- 1 H-pyrazole, as white solid. LCMS calc. = 288.96; found = 288.86 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 37

34
[ 352-33-0 ]
[ 4522-35-4 ]
[ 1621525-04-9 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 11 l-(4-Chlorophenyl)-3-iodo-lH-pyrazole To 3 -iodo- 1 H-pyrazole (743 mg, 3.83 mmol) in DMSO (10 mL) at 0 C, was added sodium hydride (60% in mineral oil, 184 mg, 4.60 mmol). The reaction was warmed to 25 C and stirred for 60 min before l-chloro-4-fluorobenzene (500 mg, 4.13 mmol) was added. The reaction mixture was stirred at 90 C for 2 days before quenching by the addition of water. The reaction mixture was extracted with EtOAc. The combined organic extracts were dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 0-20% EtOAc in hexanes) to give product, as a white solid. LCMS calc. = 304.93; found = 304.92 (Mu+Eta)+. NMR (500 MHz, CDC13): delta 7.73 (d, J= 2.5 Hz, 1 H); 7.64-7.61 (m, 2 H); 7.46-7.43 (m, 2 H); 6.66 (d, J= 2.5 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 37

35
[ 4522-35-4 ]
[ 60702-69-4 ]
[ 1621525-05-0 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 12 2-Chloro-4-("3-iodo-lH-pyrazol-l-yl)benzonitrile To a solution of 3-iodo-lH-pyrazole (702 mg, 3.62 mmol) in anhydrous DMSO (10 mL) was added NaH (183 mg, 4.58 mmol) at 0 C. The mixture was stirred for 30 min at 0 C, followed by the addition of 2-chloro-4-fluorobenzonitrile (534 mg, 3.43 mmol) in DMSO (1 mL). The resulting mixture was stirred at 90 C overnight. The mixture was cooled to room temperature, quenched with water (20 mL) and extracted with EtOAc (3 x 60 mL). The organic layer was collected and dried over Na2S04. The solvent was removed in vacuo to give the crude product. This was purified by flash chromatography (Combiflash ISCO, 24 g, Biotage Si column, ~60 mL/min, 100% hexanes for 5 min, gradient to 100%) EtOAc in hexanes over 15 min ) to afford 2-chloro-4-(3-iodo-lH-pyrazol-l-yl)benzonitrile. LCMS calc. = 329.93; found = 330.06 (M+H)+. ]H NMR (500 MHz, CD3OD): 8 8.30 (d, J= 2.7 Hz, 1 H); 8.13 (s, 1 H); 7.92 (s, 2 H); 6.77 (, d, J= 2.7 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 38

36
[ 372-47-4 ]
[ 4522-35-4 ]
[ 1621525-07-2 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 14 3-(3-Iodo-lH-pyrazol-l-yl)pyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (1.00 g, 5.16 mmol) in DMSO (15.1 mL) was added sodium hydride (60% in oil, 0.247 g, 6.19 mmol), and stirred for 0.5 h before 3- fluoropyridine (0.443 mL, 5.16 mmol) was added. The reaction mixture was stirred at 90 C overnight. This was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 40 g, 0-50 % EtOAc in hexanes) to give 3-(3- iodo-lH-pyrazol-l-yl)pyridine, as a white solid. LCMS calc. = 271.96; found = 271.85 (M+H)+. 1H NMR (500 MHz, CDC13): delta 8.93 (d, J= 2.5 Hz, 1 H); 8.57 (dd, J= 4.7, 1.1 Hz, 1 H); 8.04 (d, J= 8.4 Hz, 1 H); 7.79 (d, J= 2.5 Hz, 1 H); 7.41 (dd, J = 8.3, 4.8 Hz, 1 H); 6.68 (d, J= 2.4 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 39

37
[ 936841-73-5 ]
[ 4522-35-4 ]
[ 1621525-08-3 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 15 5-(3-Iodo-lH-pyrazol-l -yl)-2-(trifluorometyl)pyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.588 g, 3.03 mmol) in DMSO (15.0 mL) was added sodium hydride (60% in oil, 0.145 g, 3.64 mmol) and stirred for 0.5 h before 5-fluoro- 2-(trifluoromethyl)pyridines added. The reaction mixture was stirred at 90 C overnight. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by passing through the silica gel funnel with CH2C12 to give 5-(3-iodo-lH-pyrazol-l -yl)-2- (trifiuorometyl)pyridine, as a yellow solid. LCMS calc. = 339.95; found = 339.89 (M+H)+. 1H NMR (500 MHz, CDC13): delta 9.03 (d, J= 2.3 Hz, 1 H); 8.24 (dd, J= 8.4, 2.1 Hz, 1 H); 7.86 (d, J= 2.5 Hz, 1 H); 7.80 (d, J= 8.5 Hz, 1 H); 6.73 (d, J = 2.6 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 39-40

38
[ 1099597-96-2 ]
[ 4522-35-4 ]
[ 1621525-09-4 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 16 3-(3-Iodo-lH-pyrazol-l-yl)-5-(trifluorometyl pyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.70 g, 3.61 mmol), in DMSO (15.0 mL) was added sodium hydride (60% in oil, 0.159 g, 3.97 mmol), and stirred for 0.5 h before 3- fluoro-5-trifluoromethylpyridine (0.596 g, 3.61 mmol) was added. The reaction mixture was stirred at 90 C overnight. This was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 40 g, 0-20 % EtOAc in hexanes) to give 3-(3-iodo-lH-pyrazol-l-yl)-5-(trifluorometyl)pyridine, as a white solid. LCMS calc. = 339.95; found = 339.86 (M+H)+. 1H NMR (500 MHz, CDC13): delta 9.12 (br s, 1 H); 8.83 (br s, 1 H); 8.32 (br s, 1 H); 7.85 (br s, 1 H); 6.73 (d, J= 1.7 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 40

39
[ 696-42-4 ]
[ 4522-35-4 ]
[ 1621525-10-7 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 17 5-(3-Iodo-lH-pyrazol-l-yl)nicotinonitrile To 3-iodo-l/J-pyrazole (500 mg, 2.58 mmol) in DMSO (2.6 mL) at 0 C, was added sodium hydride (60% in mineral oil, 113 mg, 2.84 mmol). The reaction was warmed to 25 C and stirred for 60 min before 5-fluoronicotinonitrile (315 mg, 2.58 mmol) was added. The reaction mixture was stirred at 85 C for 5 h before quenched by the addition of water. The reaction mixture was extracted with EtOAc. The combined organic extracts were dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 0-50% EtOAc in hexanes) to afford 5-(3-iodo-lH-pyrazol-l-yl)nicotinonitrile, as a white solid. LCMS calc. = 296.96; found = 296.88 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 40-41

40
3,4-difluoropyridine [ No CAS ]
[ 4522-35-4 ]
[ 1621525-11-8 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 18 3 -Fluoro-4-(3 -iodo- 1 H-pyrazol- 1 - vDpyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.70 g, 3.61 mmol) in DMSO (15.1 mL) was added sodium hydride (60% in oil, 0.159 g, 3.97 mmol) and stirred for 0.5 h before 3,4- difluoro pyridine (0.415 g, 3.61 mmol) was added. The reaction mixture was stirred at 90 C for 2.5 h. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 40 g, 0-20 % EtOAc in hexanes) to give 3- fluoro-4-(3-iodo-lH-pyrazol-l-yl)pyridine, as a white solid. LCMS calc. = 289.95; found = 289.92 (M+H)+. NMR (500 MHz, CDC13): delta 8.61 (d, J= 3.8 Hz, 1 H); 8.48 (d, J= 5.4 Hz, 1 H); 8.02 (d, J= 2.4 Hz, 1 H); 8.00 (d, J= 5.4 Hz, 1 H); 6.70 (d, J= 2.5 Hz, 1 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 41

41
[ 766-16-5 ]
[ 4522-35-4 ]
[ 1621525-12-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 0 - 90℃; for 4.5h;	INTERMEDIATE 19 4-(3 -Iodo- 1 H-p yrazol- 1 - ylV 2-methylpyridine To a stirred solution of 4-fluoro-2-methylpyridine (1 g, 9.0 mmol) and 3-iodo-lH- pyrazole (1.76 g, 9.1 mmol) in DMSO was added NaH ( 60% in oil, 0.45 g, 11.25 mmol) in portion at 0 C. The mixture was stirred at room temparature for 30 min or until bubbling ceased, then warmed to 90 C and stirred at 90 C for 4 h. The reaction mixture was cooled to room temperature, partitioned between EtOAc and water. The aqueous was extracted with EtOAc three times. The organic phases were combined, dried over Na2S04 and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Isco CombiFlash, 120 g Silica gel column, 0-100% EtOAc in hexanes) to afford 4-(3-iodo-lH-pyrazol-l-yl)-2-methylpyridine. LCMS calc. = 285.98; found = 285.92 (M+H)+. NMR (500 MHz, CDC13): delta 8.57 (br s, 1 H); 7.87 (br s, 1 H); 7.56 (br s, 1 H); 7.35 (br s, 1 H); 6.71 (br s, 1 H); 2.66 (s, 3 H)

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 41-42

42
[ 1142194-24-8 ]
[ 4522-35-4 ]
[ 1621525-13-0 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 21 4-(3 -Iodo- 1 H-pyrazol- 1 -ylV2-isopropoxypyridine To a solution of <strong>[4522-35-4]3-iodopyrazole</strong> (0.30 g, 1.547 mmol) in DMSO (7.73 mL) was added sodium hydride (60% in oil, 0.068 g, 1.701 mmol). The resulting mixture was stirred for 0.5 h before 4-bromo-2-isopropoxypyridine (0.334 g, 1.547 mmol) was added. The reaction mixture was stirred at 80 C overnight. The reaction was quenched by the addition of water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 24 g, 0-10 % EtOAc in hexanes) to give 4-(3 -iodo- 1 H-pyrazol- l-yl)-2-isopropoxypyridine, as a white solid. LCMS calc. = 330.00; found = 329.91. (Mu+Eta)+. NMR (500 MHz, CDC13): 5 8.17 (d, J= 5.7 Hz? 1 H); 7.78 (d, J= 2.6 Hz, 1 H); 7.20 (dd, J= 5.7, 1.9 Hz, 1 H); 6.93 (d, J= 1.9 Hz, 1 H); 6.64 (d, J= 2.5 Hz, 1 H); 5.34 (m, 1 H); 1.36 (d, J = 6.2 Hz, 6 H).

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 43

43
[ 1321518-05-1 ]
[ 4522-35-4 ]
[ 1621525-14-1 ]

Yield	Reaction Conditions	Operation in experiment
	With [2,2]bipyridinyl; copper diacetate; sodium carbonate; In 1,2-dichloro-ethane; at 70℃;Inert atmosphere;	INTERMEDIATE 22 4-(3-Iodo-lH-pyrazol-l-yl -N7V-dimethylpyridin-2-amine To a suspension of 3-iodo-lH-pyrazole (100 mg, 0.516 mmol) and N,N-dimethyl-4- (4,4,5, 5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridin-2-amine (1 2 mg, 0.773 mmol), Na2C03 (109 mg, 1.031 mmol) in anhydrous dichloroethane (4 mL) added a suspension of Cu(OAc)2 (94 mg, 0.516 mmol) and 2,2'-bipyridine (81 mg, 0.516 mmol) in dichloroethane (4 mL). The reaction was stirred at 70 C under N2 overnight. The mixture was filtered through the Celite and washed with EtOAc (5 mL x 3), the filtrate was collected and removed in vacuo to give the crude product. This was purified by flash chromatography (ISCO Combiflash, lOg, Biotage Si column, -30 mL/min, 100% hexanes 5 min, gradient to 100% EtOAc in hexanes 15 min) to afford 4-(3-iodo-lH-pyrazol-l-yl)-N,N-dimethylpyridin-2-amine. LCMS calc. = 315.01 ; found = 315.10 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 43-44

44
[ 886371-79-5 ]
[ 4522-35-4 ]
[ 1621525-15-2 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 23 Methyl 4-(3-iodo- lH-pyrazol- 1 -yl)picolinate To 3-iodo-lH-pyrazole (625 mg, 3.22 mmol) in DMSO (15 mL) at 0 C,was added sodium hydride (60% in mineral oil, 155 mg, 3.87 mmol). The reaction was stirred for 30 min before methyl 4-fluoropicolinate (500 mg, 3.22 mmol) was added and the reaction was stirred at 90 C for 4.5 h. The reaction mixture was quenched by the addition of water and the mixture was extracted with EtOAc. The combined organic extracts were dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 0-100%) EtOAc in hexanes) to afford methyl 4-(3-iodo-lH-pyrazol-l-yl)picolinate, as a colorless solid. LCMS calc. = 329.97; found = 329.88 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 44

45
[ 57883-26-8 ]
[ 4522-35-4 ]
[ 1621525-16-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 25℃;	INTERMEDIATE 25 2-Ethoxy-4-(3-iodo-lH-pyrazol-l-yl)pyridine Anhydrous DMF was added to a mixture of 4-bromo-2-ethoxypyridine (312 mg, 1.55 mmol), 3-iodo-lH-pyrazole (300 mg, 1.55 mmol) and K2C03 (641 mg, 4.64 mmol). The mixture was stirred at 25 C overnight. The reaction mixture was then quenched with water and extracted with with EtOAc. The organic layer was dried (Na2S04) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Isco Combiflash Rf, RediSep Silica 24 g 0-100% EtOAc in hexanes) to afford 2-ethoxy-4-(3-iodo-lH-pyrazol-l-yl)pyridine. LCMS calc. = 314.99; found = 315.90 (M+H)+.

Reference： [1]Patent: WO2014/120346,2014,A1 .Location in patent: Page/Page column 45

46
[ 4522-35-4 ]
[ 109-92-2 ]
3-iodo-1-(1-ethoxyethyl)-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With trifluoroacetic acid; In dichloromethane; at 20 - 33℃;	General procedure: To a solution of pyrazole 1-13 (1 equiv.) and trifluoroacetic acid (0.01 equiv.) in dichloromethane(for 1 mol of pyrazole - 1 L of dichloromethane were used) ethyl vinyl ether (1.27 equiv.) wasadded dropwise, keeping the temperature between 28-32 C (exothermic reaction) and left to stir atroom temperature for 12-78 hours. Dichloromethane was washed with saturated NaHCO3 solution(1 × 250 mL - for 1 L of dichloromethane) then with deionized H2O (1 × 250 mL). Organic layerwas dried with anhydrous Na2SO4, and evaporated under reduced pressure. Products were purifiedby distillation or recrystallization.

Reference： [1]ARKIVOC,2014,vol. 2014,p. 54 - 71

47
[ 24424-99-5 ]
[ 4522-35-4 ]
tert-butyl 3-iodo-1H-pyrazole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.5%	With triethylamine; In dichloromethane; at 20℃;	General procedure: To a solution of pyrazole 1-5 (1 equiv.) and triethylamine (1.5 equiv.) in dichloromethane (for 0.05mol of pyrazole - 50 mL of dichloromethane were user) Di-tert-butyl dicarbonate (1.2 equiv) wereadded at room temperature and left to stir overnight. Dichloromethane was washed with saturatedNaHCO3 solution (1×25 mL - for 50 mL of dichloromethane) then with deionized H2O (1 × 25mL). Organic layer was dried with anhydrous Na2SO4, and evaporated under reduced pressure.

Reference： [1]ARKIVOC,2014,vol. 2014,p. 54 - 71

48
[ 96-49-1 ]
[ 4522-35-4 ]
2-(3-iodo-pyrazol-1-yl)-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	In N,N-dimethyl-formamide; at 150℃; for 3h;	a. 2-(3-Iodo-pyrazol-1-yl)-ethanol (Intermediate Fa) A solution of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (500 mg, 2.6 mmol) and ethylene carbonate (238 mg, 2.70 mmol) was formed in DMF (5 mL) and heated at 150 C. for 3 h.
72%	In N,N-dimethyl-formamide; at 150℃; for 3h;	A solution of 3-iodo-lH-pyrazole (500 mg, 2.6 mmol) and ethylene carbonate (238 mg, 2.70 mmol) was formed in DMF (5 mL) and heated at 150C for 3 h. The mixture was allowed to cool then evaporated under vacuum to remove the solvent. Purification of the residue by FCC eluting with a gradient of 0-100% EtOAc in cyclohexane gave crude title compound (444 mg, 72%) as a brown oil. LCMS (Method 3): Rt 2.17 min, m/z 239 [MH+].
72%	In N,N-dimethyl-formamide; at 150℃; for 3h;	A solution of 3-iodo-lH-pyrazole (500 mg, 2.6 mmol) and ethylenecarbonate (238 mg, 2.7 mmol) was formed in DMF (5 mL) and heated at150C for 3 h. The mixture was allowed to cool then evaporated undervacuum to remove the solvent. Purification of the residue by FCC, elutingwith a gradient of 0-100% EtOAc in cyclohexane, gave crude title compound(444 mg, 72%).

In N,N-dimethyl-formamide; at 150℃; for 3h;

A solution of 3-iodo-lH-pyrazole (500 mg, 2.6 mmol) and ethylene carbonate (238 mg, 2.7 mmol) was formed in DMF (5 mL) and heated at 150C for 3 h. The mixture was allowed to cool then evaporated under vacuum to remove the solvent. Purification of the residue by FCC, eluting with a gradient of 0- 100% EtOAc in cyclohexane, gave crude title compound (444 mg, 72%). LCMS (Method 3): Rt 2.17 min, m/z 239 [MH+].

Reference： [1]Patent: US2014/364411,2014,A1 .Location in patent: Paragraph 0464; 0465
[2]Patent: WO2014/195400,2014,A1 .Location in patent: Page/Page column 101
[3]Patent: KR2016/16973,2016,A .Location in patent: Paragraph 0298-0300
[4]Patent: WO2014/194956,2014,A1 .Location in patent: Page/Page column 62

49
[ 1194-02-1 ]
[ 4522-35-4 ]
[ 1616069-58-9 ]

Reference： [1]Chemistry - An Asian Journal,2015,vol. 10,p. 1626 - 1630

50
[ 4522-35-4 ]
[ 350-46-9 ]
3-iodo-1-(4-nitrophenyl)-1H-pyrazole [ No CAS ]

Reference： [1]Chemistry - An Asian Journal,2015,vol. 10,p. 1626 - 1630

51
[ 917899-39-9 ]
[ 4522-35-4 ]

Reference： [1]Chemistry - An Asian Journal,2015,vol. 10,p. 1626 - 1630

52
[ 13269-77-7 ]
[ 4522-35-4 ]
1,1-diethoxy-3-(4-iodo-1H-pyrazol-1-yl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21 mg	With caesium carbonate; In N,N-dimethyl-formamide;	Example 0812 0812-1 Cesium carbonate (424 mg), N,N-dimethylformamide (2 mL), and <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (233 mg) were added to 2-(diethoxymethyl)oxirane (146 mg), followed by stirring at 90 C. for 1.5 hours. The reaction mixture was cooled to room temperature, water was added thereto, and the resultant product was extracted three times with ethyl acetate. An organic layer thus obtained was washed with a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate), thereby obtaining 1,1-diethoxy-3-(4-iodo-1H-pyrazol-1-yl)propan-2-ol (350 mg) as colorless oily substance. MS m/z (M+H): 341.

Reference： [1]Patent: US2015/322063,2015,A1 .Location in patent: Paragraph 3533; 3534; 3535

53
[ 7252-83-7 ]
[ 4522-35-4 ]
1-(2,2-dimethoxyethyl)-3-iodopyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.4%	With sodium hydride; In mineral oil; at 150℃; for 1h;Microwave irradiation;	To a solution of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (500 mg, 2.578 mmol) in DMF i10 ml) was addedsodium hydride (1.5 eq., 3 867 mmci, 60% dispersicn n mneral oil, 154.7 mg) and thesuspension allowed to stir or 30 mins until the gas evolution had subsoed. Bromoacetaldehyde dimethyl acetal (1.5 eq. 3.867 mmol, 649.6 mg, 0.4.54 ml) was then added dropwise and the mixtu e heated at 150 C n the microwave for an hour. The mixture was concentrated in vacuo in order to remove as much DMF possible.EtOAc and water were then added to the mixture and the organic layer separated. The aqueous layer was washed twice with. EtOAc and organics combined, dried over MgSO4 and concentrated in vacuo. The product was purified by column chromatography, MeOH/DOM (0-1 %)to give a light orange solid; (519.2 mg, 1.841 mmcl, 71.4 %?,. 1H NMR (500 MHz, CDCI3) 6 7.28 (d, J 2.3, 1 H), 6.40 (d, J 2.3, 1 H),4.62 Ct, J 5.4, 1 H), 4.20 (d, J = 5.4, 2H?j, 3.37 (?d, J = 2.4. 6H 13C NMR (126 MHz, CDCl31 6 132.61 (OH), 9:14.84 (OH), 103.29 (OH2), 94.49 (C). 55.20 (2x OH3, 54 55 (OH); MS (ES ±ve) (M+HY 304.6 (+Na).

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 4697 - 4710
[2]Patent: WO2016/185160,2016,A1 .Location in patent: Page/Page column 94

54
[ 4522-35-4 ]
[ 75-65-0 ]
1-(tert-butyl)-3-iodo-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; at 100℃; for 3h;Inert atmosphere;	To a round-bottomed flask equipped with a stifling bar and a N2 tee, <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (2.00 g, 10 mmol), 2-methylpropan-2-ol (7.64 g, 103 mmol), and concentrated sulfuric acid (1.08 g, 11 mmol) were added. The resulting mixture was heated at 100 C. for 3 hrs.

Reference： [1]Patent: KR2016/37198,2016,A .Location in patent: Paragraph 2095

55
[ 598-39-0 ]
[ 4522-35-4 ]
1-(2,2-difluoroethyl)-3-iodo-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
339 mg		A stirred solution of NaHMDS in THF (1.0 M, 3.1 mL, 3.1 mmol) was cooled in an ice water bath under Ar. <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (500 mg, 2.6 mmol) was added as a solution in DMF (1 mL), washing with additional DMF (2×1 mL). 1,1-difluoro-2-iodoethane (0.47 mL, 5.2 mmol) was added in one portion and the mixture was removed from the cold bath. After 1.25 h, the reaction mixture was diluted with water and EtOAc. The phases were separated, and the organic phase was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel (0-15% EtOAc in hexanes) to provide 1-(2,2-difluoroethyl)-<strong>[4522-35-4]3-iodo-1H-pyrazole</strong> 7.02 (339 mg). Regiochemistry was assigned by NOE studies.

Reference： [1]Patent: KR2016/37198,2016,A .Location in patent: Paragraph 3222-3224

56
[ 75-30-9 ]
[ 4522-35-4 ]
3-iodo-1-isopropyl-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%		To a solution of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (10 g, 51.55 mmol, 1 eq) in DMF (100 mL) was added NaHMDS (1 M, 61.86 mL, 1.2 eq) at 0 C. The reaction mixture was stirred at 0 C for 0.5 hours. Then a solution of 2-iodopropane (10.52 g, 61.86 mmol, 1.2 eq) in DMF (20 mL) was added dropwise to the above mixture. The reaction mixture was warmed to 25 C and stirred for 12 hours. The reaction mixture was quenched with water (100 mL) and extracted EtOAc (3 × 80 mL). The organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromatography (SiO2, petroleum ether: ethyl acetate 1:0 to 50:1) to give the title compound (6.9 g, 56% yield) as a yellow oil.1H NMR (400 MHz, CDCl3): d 7.26 (d, 1 H), 6.40 (d, 1 H), 4.56-4.48 (m, 1 H) and 1.50 (d, 6 H).
		<strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (250 mg, 1.29 mmol) was added as a solution in DMF (0.8 mL) to a 1.0 M THF solution of NaHMDS (1.5 mL, 1.5 mmol) that had been pre-cooled in an ice water bath. Additional portions of DMF (2×0.35 mL) were used to ensure complete transfer. 2-iodopropane was added in one portion and the reaction mixture was allowed to warm to r.t. After 3.5 h, the reaction mixture was diluted with saturated aqueous NH4Cl (5 mL), water (20 mL), and EtOAc (20 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (20 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated to afford a crude residue that was purified by silica gel chromatography to provide 3-iodo-1-isopropyl-1H-pyrazole (4.02).

Reference： [1]Patent: WO2019/211463,2019,A1 .Location in patent: Page/Page column 178; 179
[2]Patent: KR2016/37198,2016,A .Location in patent: Paragraph 2523-2525; 3218-3220

57
[ 26272-85-5 ]
[ 4522-35-4 ]
3-iodo-1-(oxetan-3-yl)-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
414 mg	With sodium hexamethyldisilazane; In tetrahydrofuran; N,N-dimethyl-formamide; at 45℃; for 76h;Cooling with ice;	<strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (503 mg, 2.6 mmol) was added as a solution in DMF (1 mL) to a 1.0 M THF solution of NaHMDS (2.9 mL, 2.9 mmol) that had been pre-cooled in an ice water bath. Additional portions of DMF (2×1 mL) were used to ensure complete transfer. 3-iodooxetane (0.41 mL, 4.7 mmol) was added in one portion and the reaction mixture was allowed to warm to r.t. After 1 h, the reaction mixture was heated to 45 C. and allowed to stir for an additional 75 h. The mixture was cooled and diluted with EtOAc, and water. The aqueous phase was extracted with EtOAc. The combined organic phase was washed with water and were dried over Na2SO4, filtered and concentrated to afford a crude residue that was purified by silica gel chromatography (0-30% EtOAc in hexanes) to provide 3-iodo-1-(oxetan-3-yl)-1H-pyrazole 7.53 (414 mg). Regiochemistry was confirmed as drawn via NOE studies.

Reference： [1]Patent: KR2016/37198,2016,A .Location in patent: Paragraph 3434-3436

58
[ 105-36-2 ]
[ 4522-35-4 ]
(3-iodo-1H-pyrazol-1-yl)ethyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.64 g		(1) a nitrogen gas atmosphere, in tetrahydrofuran (16 mL) solution of 3-iodo -1H- pyrazole (1.55 g), sodium hydride at 0 C. (purity 55%, 384 mg) and stirred for 15 minutes added.There was added dropwise a tetrahydrofuran solution (10 mL) of ethyl bromoacetate (1.06 mL), and stirred for 3 hours. Under ice-cooling, and extracted with chloroform by the addition of 1M hydrochloric acid to the reaction mixture. Organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 100: 0 ? 70: 30) to give the (3-iodo -1H- pyrazol-1-yl) colorless oil Ethyl acetate (1.64 g) It was obtained as a material.

Reference： [1]Patent: JP2015/231988,2015,A .Location in patent: Paragraph 0349; 0350

59
[ 128796-39-4 ]
[ 4522-35-4 ]
[ 1164166-10-2 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; copper diacetate; triethylamine; In dichloromethane; at 20℃; for 48h;	Dichloromethane (5.0 mL) in <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (1.03 mmol) solution, (4-(trifluoromethyl)phenyl)boronic acid (2.06 mmol), pyridine (5.15 mmol), copper (II)acetate (4.12 mmol) and triethylamine was added (3.09 mmol). The reaction mixturewas stirred at room temperature for two days. When the reaction is completed, afterremoving by filtration using Celite and the insoluble residue was filtered andconcentrated to a liquid. Purification of the crude residue by silica gel flash columnchromatography to produce a D1.

Reference： [1]Patent: KR101480674,2015,B1 .Location in patent: Paragraph 0111-0113

60
[ 4522-35-4 ]
[ 126378-11-8 ]
benzyl 5-(1H-pyrazol-3-yl)pent-4-ynoate [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 857 - 861

61
[ 1104383-06-3 ]
[ 4522-35-4 ]
[ 824-94-2 ]
tert-butyl 4-[2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-2,2-dimethyl-3-oxopiperazine-1-carboxylate [ No CAS ]
tert-butyl 4-[1-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-2,2-dimethyl-3-oxopiperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		1-(chloromethyl)-4-methoxy-benzene (2.10 mL, 15.5 mmol) was added to a stirred mixture of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (2.01 g, 10.4 mmol) and Cs2CO3 (6.70 g, 20.6 mmol) in DMF (30.0 mL). The reaction mixture was stirred at 60 C for 2 hours and then, cooled to room temperature. Water (100mL) was added and aqueous was extracted with EtOAc (3 x 50 mL). Combined organic extracts were washed with aqueous saturated NH4Cl (25 mL) solution, brine (25 mL) and dried over MgSO4. The mixture was filtered and concentrated to afford 4.06 g of crude material. The residue was adsorbed on silica using DCM and purified by silica gel chromatography to afford 3-iodo-1-[(4- methoxyphenyl)methyl]pyrazole and 5-iodo-1-[(4-methoxyphenyl)methyl]pyrazole (3.18 g, 98%) as a white solid as a ca.5:1 mixture of regioisomers. Major Regioisomer: 1H NMR (400 MHz, CDCl3) 7.23 - 7.15 (m, 3H), 7.12 (d, J = 2.3 Hz, 1H), 6.92 - 6.85 (m, 2H), 6.40 (d, J = 2.3 Hz, 1H), 5.24 (s, 2H). : ESI-MS m/z calc.313.9916, found 314.98 (M+1)+; Retention time: 0.93 minutes Using Method J A mixture of tert-butyl 2,2-dimethyl-3-oxo-piperazine-1-carboxylate (915 mg, 4.01 mmol), regioisomers mix of 5-iodo-1-[(4-methoxyphenyl)methyl]pyrazole/3- iodo-1-[(4-methoxyphenyl)methyl]pyrazole (1.51 g, 4.81 mmol), iodocopper (381.7 mg, 2.00 mmol), N,N'-dimethylethane-1,2-diamine (353.3 mg, 426.7 muL, 4.01 mmol) and K3PO4 (1.702 g, 8.02 mmol) in DMF (18.3 mL) was heated at 120 C for 3.5 hours. The reaction mixture was cooled to r.t. and filtered to remove the copper salts. The filtrate was diluted with water and aqueous was extracted twice with ethyl acetate. Organic extracts were washed with water, followed with brine, dried over Na2SO4, filtered and (0666) concentrated under reduced pressure. The recovered crude compound was purified by silica gel chromatography to give a mixture of the tert-butyl 4-[2-[(4- methoxyphenyl)methyl]pyrazol-3-yl]-2,2-dimethyl-3-oxo-piperazine-1-carboxylate and the tert-butyl 4-[1-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-2,2-dimethyl-3-oxo- piperazine-1-carboxylate (1.603 g, 96%). Major regioisomer: 1H NMR (400 MHz, DMSO-d6) 7.70 (d, J = 2.3 Hz, 1H), 7.22 - 7.11 (m, 2H), 6.91 - 6.81 (m, 2H), 6.61 (d, J = 2.3 Hz, 1H), 5.14 (s, 2H), 3.86 - 3.79 (m, 2H), 3.69 (s, 3H), 3.66 - 3.58 (m, 2H), 1.58 (s, 6H), 1.40 (s, 9H). ESI-MS m/z calc.414.2267, found 416.38 (M+1)+

Reference： [1]Patent: WO2016/154075,2016,A1 .Location in patent: Paragraph 00397-00399

62
[ 1104383-06-3 ]
[ 4522-35-4 ]
[ 824-94-2 ]
1-[2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-3,3-dimethylpiperazin-2-one hydrochloride [ No CAS ]
1-[1-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-3,3-dimethylpiperazin-2-one hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		1-(chloromethyl)-4-methoxy-benzene (2.10 mL, 15.5 mmol) was added to a stirred mixture of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (2.01 g, 10.4 mmol) and Cs2CO3 (6.70 g, 20.6 mmol) in DMF (30.0 mL). The reaction mixture was stirred at 60 C for 2 hours and then, cooled to room temperature. Water (100mL) was added and aqueous was extracted with EtOAc (3 x 50 mL). Combined organic extracts were washed with aqueous saturated NH4Cl (25 mL) solution, brine (25 mL) and dried over MgSO4. The mixture was filtered and concentrated to afford 4.06 g of crude material. The residue was adsorbed on silica using DCM and purified by silica gel chromatography to afford 3-iodo-1-[(4- methoxyphenyl)methyl]pyrazole and 5-iodo-1-[(4-methoxyphenyl)methyl]pyrazole (3.18 g, 98%) as a white solid as a ca.5:1 mixture of regioisomers. Major Regioisomer: 1H NMR (400 MHz, CDCl3) 7.23 - 7.15 (m, 3H), 7.12 (d, J = 2.3 Hz, 1H), 6.92 - 6.85 (m, 2H), 6.40 (d, J = 2.3 Hz, 1H), 5.24 (s, 2H). : ESI-MS m/z calc.313.9916, found 314.98 (M+1)+; Retention time: 0.93 minutes Using Method J A mixture of tert-butyl 2,2-dimethyl-3-oxo-piperazine-1-carboxylate (915 mg, 4.01 mmol), regioisomers mix of 5-iodo-1-[(4-methoxyphenyl)methyl]pyrazole/3- iodo-1-[(4-methoxyphenyl)methyl]pyrazole (1.51 g, 4.81 mmol), iodocopper (381.7 mg, 2.00 mmol), N,N'-dimethylethane-1,2-diamine (353.3 mg, 426.7 muL, 4.01 mmol) and K3PO4 (1.702 g, 8.02 mmol) in DMF (18.3 mL) was heated at 120 C for 3.5 hours. The reaction mixture was cooled to r.t. and filtered to remove the copper salts. The filtrate was diluted with water and aqueous was extracted twice with ethyl acetate. Organic extracts were washed with water, followed with brine, dried over Na2SO4, filtered and (0666) concentrated under reduced pressure. The recovered crude compound was purified by silica gel chromatography to give a mixture of the tert-butyl 4-[2-[(4- methoxyphenyl)methyl]pyrazol-3-yl]-2,2-dimethyl-3-oxo-piperazine-1-carboxylate and the tert-butyl 4-[1-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-2,2-dimethyl-3-oxo- piperazine-1-carboxylate (1.603 g, 96%). Major regioisomer: 1H NMR (400 MHz, DMSO-d6) 7.70 (d, J = 2.3 Hz, 1H), 7.22 - 7.11 (m, 2H), 6.91 - 6.81 (m, 2H), 6.61 (d, J = 2.3 Hz, 1H), 5.14 (s, 2H), 3.86 - 3.79 (m, 2H), 3.69 (s, 3H), 3.66 - 3.58 (m, 2H), 1.58 (s, 6H), 1.40 (s, 9H). ESI-MS m/z calc.414.2267, found 416.38 (M+1)+ A HCl solution in dioxane (4.84 mL of 4 M, 19.3 mmol) was added to a stirred solution of the mixture of regioisomers tert-butyl 4-[2-[(4- methoxyphenyl)methyl]pyrazol-3-yl]-2,2-dimethyl-3-oxo-piperazine-1-carboxylate/ tert- butyl 4-[1-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-2,2-dimethyl-3-oxo-piperazine-1- carboxylate (1.60 g, 3.87 mmol) in DCM (16 mL). The reaction mixture was stirred 24h at room temperature and then, solvents were removed by evaporation in vacuo. The recovered gummy residue was dissolved in DCM and sonicated. Diethyl ether was added dropwise until full precipitation of the desired product in the sonicator bath. The mixture was filtered. The recovered white solid was washed with diethyl ether and dried under vacuum to give a mixture of regioisomers 1-[2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]- 3,3-dimethyl-piperazin-2-one and 1-[1-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-3,3- dimethyl-piperazin-2-one (1.153 g, 85%) as hydrochloride salt. Major isomer: 1H NMR (400 MHz, DMSO-d6) 10.07 (broad s, 1H), 7.79 (d, J = 2.3 Hz, 1H), 7.23 - 7.08 (m, 2H), 6.93 - 6.83 (m, 2H), 6.64 (d, J = 2.3 Hz, 1H), 5.18 (s, 2H), 4.04 (t, J = 5.8 Hz, 2H), 3.71 (s, 3H), 3.65 - 3.50 (m, 2H), 3.42 - 3.32 (m, 1H), 1.58 (s, 6H). ESI-MS m/z calc. 314.1743, found 315.78 (M+1)+; Retention time: 0.34 using Method J

Reference： [1]Patent: WO2016/154075,2016,A1 .Location in patent: Paragraph 00397-00400

63
[ 4522-35-4 ]
[ 824-94-2 ]
5-iodo-1-[(4-methoxyphenyl)methyl]pyrazole [ No CAS ]
3-iodo-1-[(4-methoxyphenyl)methyl]pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h;	1-(chloromethyl)-4-methoxy-benzene (2.10 mL, 15.5 mmol) was added to a stirred mixture of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (2.01 g, 10.4 mmol) and Cs2CO3 (6.70 g, 20.6 mmol) in DMF (30.0 mL). The reaction mixture was stirred at 60 C for 2 hours and then, cooled to room temperature. Water (100mL) was added and aqueous was extracted with EtOAc (3 x 50 mL). Combined organic extracts were washed with aqueous saturated NH4Cl (25 mL) solution, brine (25 mL) and dried over MgSO4. The mixture was filtered and concentrated to afford 4.06 g of crude material. The residue was adsorbed on silica using DCM and purified by silica gel chromatography to afford 3-iodo-1-[(4- methoxyphenyl)methyl]pyrazole and 5-iodo-1-[(4-methoxyphenyl)methyl]pyrazole (3.18 g, 98%) as a white solid as a ca.5:1 mixture of regioisomers. Major Regioisomer: 1H NMR (400 MHz, CDCl3) 7.23 - 7.15 (m, 3H), 7.12 (d, J = 2.3 Hz, 1H), 6.92 - 6.85 (m, 2H), 6.40 (d, J = 2.3 Hz, 1H), 5.24 (s, 2H). : ESI-MS m/z calc.313.9916, found 314.98 (M+1)+; Retention time: 0.93 minutes Using Method J

Reference： [1]Patent: WO2016/154075,2016,A1 .Location in patent: Paragraph 00397; 00398

64
[ 285-69-8 ]
[ 4522-35-4 ]
C₇H₉IN₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34.63%		Example 234. Synthesis of 3-fluoro-2-(4-(l-((3R,4R)-4- hydroxytetrahydrofuran-3-yl)-lH-pyrazol-3-yl)-5-oxo-6,7-dihydro-5H-pyrrolo[3,4- b]pyridin-2-yl)benzonitrile, 1-234 Synthesis of compound 234.2. To a solution of 234.1 (5.0g, 25.77mmol, 1.0 eq) in THF (15mL) was added LDA (2M in THF ) (14mL, 28.33mmol, 1.1 eq) at -78°C. Reaction mixture was stirred at -40 °C for lh. To this added solution of 3,6-dioxabicyclo[3.1.0]hexane (1.77g, 20.61mmol, 0.8eq) in THF (lOmL). Reaction mixture was stirred at room temperature for lh and heated at 80 °C for 2 4h .Upon completion of the reaction, mixture was transferred into water, and extracted with EtOAc. Organic layers were combined, washed with brin, dried over Na2S04 and concentrated under reduced pressure to pressure to obtain crude which was purified by column chromatography to furnish 234.2 (2.5 g, 34.63percent). MS(ES): m/z 281.2 [M+H]+.

Reference： [1]Patent: WO2017/40757,2017,A1 .Location in patent: Paragraph 001051-001052

65
[ 4522-35-4 ]
[ 84476-99-3 ]
C₈H₅FIN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 80 - 90℃; for 6h;	To a solution of 180 (100.00mg, 515.54 umol) and 83 (71.19mg, 618.65umol) in DMF (3mL) was added solid C52CO3 (251.96mg, 773.3lumol) in one charge at room temperature. It was stilTed at 8090C for 6 hours. After cooling, water (i0mL) was added into the mixture with stirring at ice bath siowly. Gradually, solid was formed. It was filtrated. The residue was theproduct 198 (70.00 mg, cnde) which was used for next step directly.LCMS: m/z, 290.0 (M+H)t?HNMR (400 MFIz, CDCI3): 6.62 (d, .1=2.8 Hz, I H), 7.53-7.58 (in, I H), 7.97.00 (in, 1 H), 8.24 (d, J2.4 Hz, I H?), 8.31 (d, J=2.4 Hz, 1 H).

Reference： [1]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 104; 105

66
[ 872041-86-6 ]
[ 4522-35-4 ]
C₈H₅FIN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.82%	With pyridine; pyridine N-oxide; oxygen; copper diacetate; In dichloromethane; at 20℃; for 48h;	To a mixture of compound 180(30000mg, 1 5Smmol) and 102(32762mg, 232mmol) in DCM (2OrnL). was added pyridine (367.02mg, 4.64mmol), Cu(OAc)2(561.83mg, 3.O9mmoi) and i oxidopyridin-i--iurn (442.21 mg, 4.6Smmol, 3.OOEq) in one portion at room temperature. The mixture was stirred at room temperature for 48 hours under 02 protected. LCMS showed thereaction was completed. The mixture was filtrated and the filtrate was concentrated in reduced pressure. The residue was dissolved in ethyl acetate (4OmL). The organic phase was washed with water (3OmLx2), saturated brine (3OmLxi), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography to afford product 206(380.00mg. yield: 84.82%).LCM: m/z, 2899M+H).

Reference： [1]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 109

67
[ 372-48-5 ]
[ 4522-35-4 ]
C₈H₆IN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 90℃; for 4h;	To a solution of 180 (100.00mg, 515.S4umol) and 207(60.06mg, 618.6Sumol) in DMF (3mL) was added solid Cs2C03 (251.96mg, 773.3iumoi) in one portion at room temperature. It was stirred at 90C for 4 hours, After cooling, water (2OinL) was added into the mixture with stirring at ice bath slowly. Gradually, solid was formed. it was filtrated to afford the product 208(80.00mg, crude), which was used for next step directly.LCMS: m/z, 272.0 (M4-H.

Reference： [1]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 110

68
[ 64248-63-1 ]
[ 4522-35-4 ]
C₁₀H₅FIN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.50 g	With caesium carbonate; In N,N-dimethyl-formamide; at 29 - 70℃; for 2h;	To a mixture of compound 168(2.00g. 10.3 Immol) and 16 (1.72g. 12.37mmol) in DMF (2OmL), was added C52CO3(672g, 20.62mmoi) in one portion at 29CThe mixture was heated to 70C and stirred for 2 hours. LCMS showed the reaction was completed. The mixture was cooled to29C and concentrated in reduced pressure at 40C. The residue was poured into water (4OmL) and stilTed for 5 minutes. The aqueous phase was extracted with EtOAc(8OrnLx2). The combined organic phase was washed with saturated brine (2OmL), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography to afford product 169 (150g. yield: 4647%). ?H NMR (400 MHz, CDCI3): c37.62- 7.84 (m, 3H), 7.28-7.26 (m, I H), 6.68-6.67 (m, I H).

Reference： [1]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 95

69
[ 64248-63-1 ]
[ 4522-35-4 ]
C₁₀H₅FIN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67.08%	With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 1.5h;Inert atmosphere;	To a mixture of 180 (193.97mg, i.OOrnrnol) and 28 (139.10mg, i.OOrnmol) in DMF (5rnL), was added C52CO3 (325.82mg, 1 .OOmmol) in one portion at room temperature. The mixture was then heated to 80uC for 1 5 hours under N2 atmosphere. ILC showed the reaction was completed. Themixture was cooled to room temperature and was then poured into water (i5mL) slowly. A white solid precipitated out from the mixture, filtered off. The solid was dried to afford product 197 (300.00 mg, yield: 67.08%).LCMS: m/, 313.9 (M±H.

Reference： [1]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 103; 104

70
[ 76513-69-4 ]
[ 4522-35-4 ]
[ 220299-49-0 ]

Reference： [1]Organic Letters,2017,vol. 19,p. 6033 - 6035

71
2-(tert-butyl) 3-ethyl (1R,3S,5S)-5-(((methyl sulfonyl)oxy)methyl)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate [ No CAS ]
[ 4522-35-4 ]
2-tert-butyl 3-ethyl (1R,3S,5R)-5-[(3-iodopyrazol-1-yl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.448 g		To a solution of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (0.653 g, 3.367 mmol) in THF (10 mL) was added sodium hydride (0.124 g, 3.108 mmol) with stirring at room temperature under argon. After15 minutes, 2-tert-butyl 3-ethyl (1R,3S,5S)-5-[(methanesulfonyloxy)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate 28-51 (0.941 g, 2.59 mmol) in THF (10 mL) was added. The reaction mixture was stirred at room temperature for 2 days. NH4C1 aqueous solution was added, and the organic phase was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (MeOH in DCM 0-10%) to provide 2-tert-butyl 3-ethyl (1R,3S,5R)- 5-[(3 -iodopyrazol- 1 -yl)methyl]-2-azabicyclo[3.1. 0]hexane-2,3 -dicarboxylate 28-S2 (0.448 g) as an oil.

Reference： [1]Patent: WO2018/160892,2018,A1 .Location in patent: Paragraph 0973; 0974

72
[ 50824-05-0 ]
[ 4522-35-4 ]
[ 1379615-65-2 ]

Reference： [1]ACS Medicinal Chemistry Letters,2018,vol. 9,p. 1205 - 1210

73
[ 110-87-2 ]
[ 4522-35-4 ]
3-iodo-1-tetrahydropyran-2-ylpyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With toluene-4-sulfonic acid; In tetrahydrofuran;Reflux;	A mixture of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (5 g, 25.78 mmol), 3,4-dihydro-2H-pyran (10 g, 118.88 mmol), p-TsOH (900 mg, 5.23 mmol) in tetrahydrofuran (100 mL) was refluxed overnight. The reaction mixture was cooled to room temperature and washed with sat. NaHCO3 (20 mL). The organic layer was separated, dried over Na2SO4, filtered and evaporated. The residue was purified with silica-gel column chromatography (PE:EA=20:1 to 10:1) to give 3-iodo-1-tetrahydropyran-2-yl-pyrazole (7 g, 98% yield) as a light yellow oil. LCMS (ESI) [M+Na]+=300.9. 1H NMR (400 MHz, CDCl3) delta 7.45 (d, J=2.4 Hz, 1H), 6.46 (d, J=2.4 Hz, 1H), 5.39-5.36 (m, 1H), 4.08-4.04 (m, 1H), 3.72-3.66 (m, 1H), 2.10-2.01 (m, 2H), 1.73-1.54 (m, 4H).
1.4 g	With toluene-4-sulfonic acid; In dichloromethane; at 20℃; for 2h;	To a mixture of <strong>[4522-35-4]3-iodo-1H-pyrazole</strong> (1 g, 5.16 mmol) and p-TsOH (88 mg, 0.52 mmol) in DCM (15 mL) was added DHP (0.56 mL, 6.19 mmol) and stirred atr.t. for2 hr. The reaction mixture was washed with satd. NaHCO3 and brine, dried over anhy. Na2SO4 and concentrated. The residue was purified by flash chromatography (silica gel, 0 -. 10% EtOAcin PE) to give 3-iodo-1-(oxan-2-yl)-1H-pyrazole (1.4 g). LC-MS (m/z 279 (M÷H).

Reference： [1]Patent: US2018/282328,2018,A1 .Location in patent: Paragraph 1154; 1155
[2]Patent: WO2019/35863,2019,A1 .Location in patent: Page/Page column 135

74
[ 344-19-4 ]
[ 76513-69-4 ]
[ 4522-35-4 ]
[ 60290-21-3 ]
C₂₂H₂₄Cl₂FN₅OSi [ No CAS ]
C₂₂H₂₄Cl₂FN₅OSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		NaH (60% dispersion in mineral oil, 143 mg, 3.57 mmol) was added to a stirred solution of 3-iodo-lH-pyrazole [4522-35-4] (659 mg, 4.00 mmol) in DMF (20 mL) at 0 C under N2 atmosphere. The mixture was stirred at room temperature for 30 min. 2- (Trimethylsilyl)ethoxymethyl chloride [76513-69-4] (0.66 mL, 3.74 mmol) was added at 0 C and the reaction mixture was stirred at room temperature for 16 h. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, gradient from 0/100 to 10/90). The desired fractions were collected and concentrated in vacuo to afford a mixture of 1-188 and 1-189 (965 mg, 86%).; Cul (28.3 mg, 0.15 mmol), N,N?-dimethylcyclo hexane- 1, 2-diamine (46.9 uL, 0.30 mmol) and K2C03 (411 mg, 2.98 mmol) were added to a solution of 1-188 and 1-189 (965 mg, 2.98 mmol) in l,4-dioxane (10 mL) in a sealed tube while nitrogen was bubbling. After 10 min, 4-chloro-lH-pyrrolo[3,2-c]pyridine [60290-21-3] (227 mg, 1.49 mmol) was added. The reaction mixture was stirred at room temperature for 10 min, and at 100 C for 20 h. The mixture was diluted with water and extracted with EtOAc. The combined organic extarcts were dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, gradient from 0/100 to 15/85). The desired fractions were collected and concentrated in vacuo to afford a mixture of 1-190 and I- 191 (270 mg, 51%).; Pd2dba3 (39.1 mg, 42.6 pmol), XantPhos (61.7 mg, 0.11 mmol) and CS2CO3 (521 mg, 1.60 mmol) were added to a solution of 1-190 and 1-191 (372 mg mg, 1.07 mmol) in anhydrous DMF (12 mL) in a sealed tube while nitrogen was bubbling. After 10 min, 2,6-dichloro-4-fluoroaniline [344-19-4] (249 mg, 1.39 mmol) was added. The reaction mixture was stirred at room temperature for 10 min, and at 100 C for 20 h. The mixture was filtered over a pad of Celite and the filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, gradient from 0/100 to 100/0).). The desired fractions were collected and concentrated in vacuo to afford a mixture of I- 192 and 1-193 (376 mg, 71 %).

Reference： [1]Patent: WO2019/243535,2019,A1 .Location in patent: Page/Page column 93-94

75
[ 76513-69-4 ]
[ 4522-35-4 ]
[ 632297-52-0 ]
3-iodo-1-SEM-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		NaH (60% dispersion in mineral oil, 143 mg, 3.57 mmol) was added to a stirred solution of 3-iodo-lH-pyrazole [4522-35-4] (659 mg, 4.00 mmol) in DMF (20 mL) at 0 C under N2 atmosphere. The mixture was stirred at room temperature for 30 min. 2- (Trimethylsilyl)ethoxymethyl chloride [76513-69-4] (0.66 mL, 3.74 mmol) was added at 0 C and the reaction mixture was stirred at room temperature for 16 h. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, gradient from 0/100 to 10/90). The desired fractions were collected and concentrated in vacuo to afford a mixture of 1-188 and 1-189 (965 mg, 86%).

Reference： [1]Patent: WO2019/243535,2019,A1 .Location in patent: Page/Page column 93

76
[ 76513-69-4 ]
[ 4522-35-4 ]
[ 60290-21-3 ]
C₁₆H₂₁ClN₄OSi [ No CAS ]
C₁₆H₂₁ClN₄OSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		NaH (60% dispersion in mineral oil, 143 mg, 3.57 mmol) was added to a stirred solution of 3-iodo-lH-pyrazole [4522-35-4] (659 mg, 4.00 mmol) in DMF (20 mL) at 0 C under N2 atmosphere. The mixture was stirred at room temperature for 30 min. 2- (Trimethylsilyl)ethoxymethyl chloride [76513-69-4] (0.66 mL, 3.74 mmol) was added at 0 C and the reaction mixture was stirred at room temperature for 16 h. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, gradient from 0/100 to 10/90). The desired fractions were collected and concentrated in vacuo to afford a mixture of 1-188 and 1-189 (965 mg, 86%).; Cul (28.3 mg, 0.15 mmol), N,N?-dimethylcyclo hexane- 1, 2-diamine (46.9 uL, 0.30 mmol) and K2C03 (411 mg, 2.98 mmol) were added to a solution of 1-188 and 1-189 (965 mg, 2.98 mmol) in l,4-dioxane (10 mL) in a sealed tube while nitrogen was bubbling. After 10 min, 4-chloro-lH-pyrrolo[3,2-c]pyridine [60290-21-3] (227 mg, 1.49 mmol) was added. The reaction mixture was stirred at room temperature for 10 min, and at 100 C for 20 h. The mixture was diluted with water and extracted with EtOAc. The combined organic extarcts were dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, gradient from 0/100 to 15/85). The desired fractions were collected and concentrated in vacuo to afford a mixture of 1-190 and I- 191 (270 mg, 51%).

Reference： [1]Patent: WO2019/243535,2019,A1 .Location in patent: Page/Page column 93-94

77
diethyl 2-(((2R,3R,4R,5R)-3,4-diacetoxy-5-(6-N,N’-(bis-(tert-butoxycarbonyl)amino)-2-chloro-9H-purin-9-yl)-3-ethynyltetrahydrofuran-2-yl)methoxy)malonate [ No CAS ]
[ 4522-35-4 ]
diethyl 2-(((2R,3R,4R,5R)-3-(( 1H-pyrazol-3-yl)ethynyl)-3,4-diacetoxy-5-(6-N,N'-(bis-(tert-butoxycarbonyl)amino)-2-chloro-9H-purin-9-yl)tetrahydrofuran-2-yl)methoxy)malonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; palladium bis[bis(diphenylphosphino)ferrocene] dichloride; triethylamine; at 60℃;Inert atmosphere;	To a mixture of 3-iodo-liT-pyrazole (407 mg, 2.1 mmol), PdCh(PPh3)2 (82 mg, 0.12 mmol), Cul (22 mg, 0.12 mmol), and Et3N (10 mL) in THF (10 mL) under argon atmosphere was added diethyl 2-(((2f?,3f?,4f?,5f?)-3,4-diacetoxy-5-(6-Ar,/V?-(bis-(/er/-butoxycarbonyl)- amino)-2-chloro-9//-purin-9-yl)-3-ethynyltetrahydrofuran-2-yl) ethoxy)malonate (1 g, 1.2 mmol). The resulting mixture was stirred at 60 C overnight before it was allowed to cool to room temperature and the organic volatile was removed under reduced pressure. The resulting crude residue was purified by flash silica gel column chromatography (60-100% EtOAc in hexanes) to provide diethyl 2-(((2R,3R,4R, 5A>)-3-(( l//-pyrazol-3-yl)ethynyl)-3,4- diacetoxy-5-(6-Af,Ap-(bis-(/c77-butoxycarbonyl)amino)-2-chloro-9//-purin-9-yl)tetrahydro- furan-2-yl)methoxy)malonate as a solid.

Reference： [1]Patent: WO2019/246403,2019,A1 .Location in patent: Page/Page column 128-129

78
3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trimethylsilyl)phenyl trifluoromethanesulfonate [ No CAS ]
[ 4522-35-4 ]
3-methoxy-5-(1H-pyrazol-3-yl)-2-(trimethylsilyl)phenyl triflate [ No CAS ]