[ CAS No. 32111-21-0 ] {[proInfo.proName]}

Name: 32111-21-0|2-Iodopyrazine|97%
Brand: Ambeed
SKU: A102067
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2D 3D

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Quality Control of [ 32111-21-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 32111-21-0 ]

SDS Specification

Alternatived Products of [ 32111-21-0 ]

Product Details of [ 32111-21-0 ]

CAS No. :	32111-21-0	MDL No. :	MFCD01319019
Formula :	C₄H₃IN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OYWPFIUVDKHHGQ-UHFFFAOYSA-N
M.W :	205.98	Pubchem ID :	642841
Synonyms :

Calculated chemistry of [ 32111-21-0 ]

Physicochemical Properties

Num. heavy atoms :	7
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	34.75
TPSA :	25.78 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.2 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.21
Log Po/w (XLOGP3) :	0.5
Log Po/w (WLOGP) :	1.08
Log Po/w (MLOGP) :	0.13
Log Po/w (SILICOS-IT) :	2.06
Consensus Log Po/w :	1.0

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.07
Solubility :	1.77 mg/ml ; 0.00858 mol/l
Class :	Soluble
Log S (Ali) :	-0.61
Solubility :	50.4 mg/ml ; 0.245 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.61
Solubility :	0.508 mg/ml ; 0.00247 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.07

Safety of [ 32111-21-0 ]

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

Application In Synthesis of [ 32111-21-0 ]

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

Upstream synthesis route of [ 32111-21-0 ]
Downstream synthetic route of [ 32111-21-0 ]

[ 32111-21-0 ] Synthesis Path-Upstream 1~9

1
[ 14508-49-7 ]
[ 32111-21-0 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: With acetic acid; sodium iodide In acetonitrile for 4.5 h; Reflux Stage #2: With sodium hydrogencarbonate In water	A reaction mixture of chloropyrazine (7.5 ml, 83 mmol), NaI (30.3 g, 202 15 mmol), HOAc (9.6 ml, 168 mmol) and H₂SO₄ (0.5 ml) in MeCN (105 ml) was heated at reflux for 4.5 hours. The solvent was removed and water (120 ml) was added. After the solution was basified with saturated NaHCO₃, it was extracted with dichloromethane (DCM) (2 x 125 ml). The DCM layers were combined, washed with saturated Na₂S₂O₃, brine and dried. The removal of solvent gave crude iodopyrazine as an oil (12.33 g, 20 71percent). Analysis by ¹H NMR showed there was less than about 10 molpercent of chloropyrazine in the oil. Another batch of chloropyrazine (50 g, 437 mmol) was also converted into crude iodopyrazine (about 65 g) by the same procedure. These two batches of crude iodopyrazine were combined and distillation of the crude iodopyrazine under reduced pressure (about 0.75 torr, bp 47°C) gave pure compound 64 g (60percent). 25¹H-NMR (CDCl₃, 300MHz) 8.40 (dd, /=1.8, 2.4Hz, IH), 8.51 (d, /=2.4Hz,lH), 8.87 (d, /=1.5Hz,lH).

Reference： [1] Tetrahedron, 1998, vol. 54, # 33, p. 9701 - 9710
[2] Patent: WO2009/114313, 2009, A2, . Location in patent: Page/Page column 15

2
[ 290-37-9 ]
[ 32111-21-0 ]

Reference： [1] Journal of Organometallic Chemistry, 2010, vol. 695, # 5, p. 775 - 780
[2] Synthesis, 2008, # 24, p. 4033 - 4035
[3] Chemical Communications, 2008, # 42, p. 5375 - 5377
[4] Journal of Organic Chemistry, 1995, vol. 60, # 12, p. 3781 - 3786
[5] Angewandte Chemie - International Edition, 2016, vol. 55, # 42, p. 13147 - 13150[6] Angew. Chem., 2016, vol. 128, # 42, p. 13341 - 13344,4

3
[ 14508-49-7 ]
[ 10034-85-2 ]
[ 32111-21-0 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium iodide In water; acetone	EXAMPLE 1 This Example illustrates the preparation of 2-iodopyrazine. 2-Chloropyrazine (6.18 g, 54 mmol) was added to a saturated solution of sodium iodide in acetone (100 ml) and water (3 ml) at reflux temperature under a nitrogen atmosphere. A solution of hydroiodic acid (3 ml of 55) in water (6 ml) was added and the mixture was heated at reflux temperature for 19 hours. The precipitated solids were removed by filtration and the filtrate concentrated under reduced pressure. Water (100 ml) was added to the residue and then solid sodium sulphite until a negative starch iodide test was obtained. Sodium hydroxide pellets were added until the pH was greater than pH 11 and the mixture was continuously extracted with diethylether. The extract was concentrated under reduced pressure and the residue fractionated to give the product as a clear oil (65percent, b. pt. 83°-85° C./18 mm Hg). NMR (90 MHz, CDCl₃): 8,88 (1H,m), 8.53 (1H,m), 8.40 (1H, m). m/z: 206 (M⁺), 127, 79 (100percent).

Reference： [1] Patent: US4975112, 1990, A,

4
[ 290-37-9 ]
[ 10199-00-5 ]
[ 32111-21-0 ]

Reference： [1] Journal of Organic Chemistry, 2007, vol. 72, # 17, p. 6602 - 6605

5
[ 5049-61-6 ]
[ 32111-21-0 ]

Reference： [1] Chemistry - A European Journal, 2018, vol. 24, # 55, p. 14622 - 14626

6
[ 290-37-9 ]
[ 1093418-77-9 ]
[ 32111-21-0 ]

Reference： [1] Synthesis, 2008, # 24, p. 4033 - 4035

7
[ 624-92-0 ]
[ 32111-21-0 ]
[ 21948-70-9 ]

Reference： [1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 9, p. 1543 - 1551

8
[ 75-07-0 ]
[ 32111-21-0 ]
[ 94777-52-3 ]

Reference： [1] Synlett, 2006, # 10, p. 1586 - 1588

9
[ 18414-58-9 ]
[ 32111-21-0 ]
[ 114457-94-2 ]

Reference： [1] Organic Letters, 2017, vol. 19, # 11, p. 2873 - 2876

[ 32111-21-0 ] Synthesis Path-Downstream 1~87

1
[ 290-37-9 ]
[ 32111-21-0 ]

Reference： [1]Journal of Organometallic Chemistry,2010,vol. 695,p. 775 - 780
[2]Synthesis,2008,p. 4033 - 4035
[3]Chemical Communications,2008,p. 5375 - 5377
[4]Journal of Organic Chemistry,1995,vol. 60,p. 3781 - 3786
[5]Angewandte Chemie - International Edition,2016,vol. 55,p. 13147 - 13150
Angew. Chem.,2016,vol. 128,p. 13341 - 13344,4

2
[ 14508-49-7 ]
[ 32111-21-0 ]

Yield	Reaction Conditions	Operation in experiment
60%		A reaction mixture of chloropyrazine (7.5 ml, 83 mmol), NaI (30.3 g, 202 15 mmol), HOAc (9.6 ml, 168 mmol) and H2SO4 (0.5 ml) in MeCN (105 ml) was heated at reflux for 4.5 hours. The solvent was removed and water (120 ml) was added. After the solution was basified with saturated NaHCO3, it was extracted with dichloromethane (DCM) (2 x 125 ml). The DCM layers were combined, washed with saturated Na2S2O3, brine and dried. The removal of solvent gave crude iodopyrazine as an oil (12.33 g, 20 71%). Analysis by 1H NMR showed there was less than about 10 mol% of chloropyrazine in the oil. Another batch of chloropyrazine (50 g, 437 mmol) was also converted into crude iodopyrazine (about 65 g) by the same procedure. These two batches of crude iodopyrazine were combined and distillation of the crude iodopyrazine under reduced pressure (about 0.75 torr, bp 47C) gave pure compound 64 g (60%). 251H-NMR (CDCl3, 300MHz) 8.40 (dd, /=1.8, 2.4Hz, IH), 8.51 (d, /=2.4Hz,lH), 8.87 (d, /=1.5Hz,lH).

Reference： [1]Tetrahedron,1998,vol. 54,p. 9701 - 9710
[2]Patent: WO2009/114313,2009,A2 .Location in patent: Page/Page column 15

3
N-[5-(tert-butyldiphenylsilanyloxy)-2-tributyltinyl-(4R)-methyl-(1SR)-(4-methoxycarbonyl-phenyl)pent-(2Z)-enyl]-P,P-diphenylphosphinamide [ No CAS ]
[ 32111-21-0 ]
N-[5-(tert-butyldiphenylsilanyloxy)-2-(pyrazin-2-yl)-(4R)-methyl-(1SR)-(4-methoxycarbonyl-phenyl)pent-(2Z)-enyl]-P,P-diphenylphosphinamide [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2005,vol. 347,p. 1605 - 1613

4
[ 21792-52-9 ]
[ 32111-21-0 ]
C₁₈H₁₀N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With copper(l) iodide; N-butylamine In diethyl ether for 6h;

Reference： [1]Lin, Chi-Fong; Lo, Yu-Hsiang; Hsieh, Ming-Chu; Chen, Yi-Hua; Wang, Jeh-Jeng; Wu, Ming-Jung [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 10, p. 3565 - 3575]

5
[ 27757-85-3 ]
[ 32111-21-0 ]
pyrazin-2-ylthien-2-ylmethylamine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 8742 - 8743

6
[ 75-07-0 ]
[ 32111-21-0 ]
[ 94777-52-3 ]

Reference： [1]Synlett,2006,p. 1586 - 1588

7
[ 32111-21-0 ]
[ 89641-18-9 ]
[ 952403-25-7 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium carbonate;palladium diacetate; triphenylphosphine; In propan-1-ol; for 4h;Heating / reflux;	Preparation 124: 2,4-Dimethoxy-5-pyrazin-2-yl-pyrimidine (Prep124); 2,4-Dimethoxy-pyrimidine-5-boronic acid (1.33 g, 7.27 mmol) was dissolved in degassed n-PrOH (20 ml) and then 2-iodo-pyrazine (1.0 g, 4.85 mmol), Na2CO3 (1.02 g, 9.70 mmol), PPh3 (127 mg, 0.48 mmol) and Pd(OAc)2 (54 mg) were added. The suspension was stirred at reflux for 4 hours. The solvent was evaporated under vacuum and the crude was partitioned between water and DCM. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH- NH4OH (99-1-0.1 ) to give 481 mg of the title compound (45% yield).MS (ES) (mlz): 219.1 [M+H]*.

Reference： [1]Patent: WO2007/113232,2007,A1 .Location in patent: Page/Page column 125

8
[ 954146-88-4 ]
[ 32111-21-0 ]
l-(4-chloro-phenyl)-9-(3-methanesulfonyl-phenyl)-2-(4-pyrazin-2-yl-phenyl)-1,9-dihydro-purin-6-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 100℃; for 4h;	Example 46; l^-Chloro-phenv?-g-rS-methanesulfonyl-phenylV?^-Pyrazin^-yl-phenvD-l^-dihvdro- purin-6-one; <n="72"/>[00174] A solution of l-(4-chloro-phenyl)-9-(3-methanesulfonyl-phenyl)-2-[4- (4,4,5,5-tetramethyl-[l ,3,2]dioxaborolan-2-yl)-phenyl]-l ,9-dihydro-purin-6-one (prepared as described in example 38, 0.75 g, 1.2 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.38 g, 1.86 mmol), cesium carbonate (0.81 g, 2.4 mmol), Pd(dppf>2Cl2 (0.09 g, 0.12 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is then heated at 100 0C for 4 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3 *). The combined organic layer is washed with brine, dried over Na2SC^, concentrated, and purified by column chromatography to afford l-(4-chloro-phenyl)-9-(3-methanesulfonyl-phenyl)-2- (4-pyrazin-2-yl-phenyl)-l,9-dihydro-purin-6-one. 1H NMR (DMSO-d6, 400 MHz) delta 9.24 (m, IH), 8.77 (s, IH), 8.70 (s, IH), 8.62 (s, IH), 8.45 (s, IH), 8.25 (d, IH), 8.04 (m, 3H), 7.90 (m, IH), 7.54 (m, 2H), 7.43 (m, 4H), 3.3 (s, 3H); LC-MS calculated for C28H19ClN6O3S (MH-H+) 555.1, found 555.0.

Reference： [1]Patent: WO2007/120454,2007,A1 .Location in patent: Page/Page column 70-71

9
[ 954146-76-0 ]
[ 32111-21-0 ]
3-[5-(4-chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 100℃; for 1.5h;	Example 47; S-fS^-Chloro-phenyl^-oxo--^-pyrazin-?-yl-pheny?^.S-dihvdro-pyrazolorB^-dipyrimidin- 1 -yll-benzonitrile; <n="73"/>[00175] A solution of 3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4 ,4,5,5-tetramethyl-[l ,3,2]- dioxaborolan-2-yl)-phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-l-yl}-benzonitrile (prepared as described in example 28, 3.6 g, 6.54 mmol) in N,N-dimethylformamide (70 mL) is degassed with argon for 0.5 h. Then <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (2.0 g, 9.82 mmol), cesium carbonate (4.2 g, 13.09 mmol), Pd(dppf)2Cl2 (0.53 g, 0.654 mmol) is added and the resulted mixture is degassed with argon for 0.5 h The reaction mixture is then heated at 100 0C for 1.5 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3 x). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography to afford 3-[5-(4-chloro-phenyl)-4-oxo-6-(4-pyrazin-2- yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-l-yl]-benzonitrile. 1H NMR (DMSO-dbeta, 400 MHz) delta 9.25 (s, IH), 8.71 (m, IH), 8.62 (m, 2H), 8.51 (m, 2H), 8.08 (d, 2H), 7.90 (m, IH), 7.88 (m, IH), 7.60 (d, 2H), 7.44 (m, 4H); LC-MS calculated for C28H16ClN7O (M+H+) 502.1, found 502.0.

Reference： [1]Patent: WO2007/120454,2007,A1 .Location in patent: Page/Page column 71-72

10
[ 954146-96-4 ]
[ 32111-21-0 ]
5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-6-(4-pyrazin-2-yl-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 100℃; for 3h;	Step C: A solution of 5-(4-chloro-phenyl)-l-(3-methanesulfonyl-phenyl)-6-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]-l,5-dihydro-pyrazolo[3,4-d]- <n="79"/>pyrimidin-4-one (8, 0.5 g, 0.829 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.26 g, 1.2 mmol), cesium carbonate (0.54 g, 1.7 mmol), Pd(dppf>2Cl2 (0.06 g, 0.08 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is then heated at 100 0C for 3 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3 ). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by preparative HPLC to afford 5-(4-chloro-phenyl)-l-(3-methanesulfonyl-phenyl)-6-(4-pyrazin- 2-yl-phenyl)-l,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (9). 1H NMR (DMSO-d6, 400 MHz) delta 9.25 (s, IH), 8.71 (m, IH), 8.68 (m, IH), 8.63 (m, IH), 8.61 (m, IH), 8.55 (m, IH), 8.09 (m, 2H), 7.95 (m, IH), 7.88 (m, IH), 7.62 (m, 2H), 7.45 (m, 4H), 3.30 (s, 3H); LC-MS calculated for C28H19ClN6O3S (M+H) 555.1, found 555.0.

Reference： [1]Patent: WO2007/120454,2007,A1 .Location in patent: Page/Page column 77-78

11
[ 954146-85-1 ]
[ 32111-21-0 ]
N-{3-[5-(4-chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-phenyl}-methanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 100℃; for 3h;	Example 55; N-(3-(5-(4-chlorophenyl'>-4-oxo-6-f4-fpyrazin-2-vDphenyl')-4.5-dihvdro- 1 H-pyrazolof 3.4- d]p yrirnidin- 1 -yDphenyPmethanesulfonamide; <n="82"/>[00189] A solution of N-(3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[ 1 ,3,2]dioxa-borolan-2-yl)phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyriinidin-l -yl} -phenyl)- methane sulfonamide (prepared as described in example 35, 0.50 g, 0.81 mmol) in N,N- dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.25 g, 1.21 mmol), cesium carbonate (0.527 g, 1.61 mmol), Pd(dppf)2Cl2 (0.06 g, 0.082 mmol) are added and the resulting solution is degassed with argon for 0.5 h. The reaction mixture is then heated at 100 0C for 3 h. The reaction mixture is cooled to it and diluted with water and extracted with ethyl acetate (3 *). The combined organic layer is washed with brine, dried over Na2SO-I, concentrated, and purified by column chromatography to afford N-{3-[5-(4- chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pytauazolo[3 ,4-d]pyrimidin- 1 -yl]- phenyl} -methane sulfonamide. 1H NMR (DMSO-d6, 400 MHz) delta 10.15 (br, 1 H), 9.26 (d, IH), 8.71 (d, IH), 8.62 (d, IH), 8.52 (s, IH), 8.06 (m, 3H), 7.82 (m, IH), 7.60 (m, 2H), 7.52 (m, IH), 7.40 (m, 4H), 7.18 (m, IH), 3.02 (s, 3H); LC-MS calculated for C28H20ClN7O3S (M+H+) 570.1, found 570.0.

Reference： [1]Patent: WO2007/120454,2007,A1 .Location in patent: Page/Page column 80-81

12
[ 954146-97-5 ]
[ 32111-21-0 ]
3-[5-(4-chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 100℃; for 2.5h;	Step B: A solution of 3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[l,3,2]-dioxa-borolan-2-yl)-phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-l-yl}-benzene sulfonamide (2, 0.650 g, 1.08 mmol).in.N,N-dimethylformamide (10 mL) is degassed with argon for 0.5 h. Then <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.33 g, 1.616 mmol), cesium carbonate (0.701 g, 2.15 mmol), Pd(dppf)2Cl2 (0.087 g, 0.107 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is then heated at 100 0C for 2.5 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3 ). The combined organic layer is washed with brine, dried over Na2SC>4, concentrated, and purified by preparative HPLC to afford 3-[5-(4-chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5- dihydro-pyrazolo[3,4-d]pyrimidin-l-yl]-benzene sulfonamide (3). 1H NMR (DMSO-d6, 400 MHz) delta 9.25 (s, IH), 8.71 (m, IH), 8.63 (d, IH), 8.58 (m, 2H), 8.45 (m, IH), 8.07 (m, 2H)5 7.80 (m, 2H), 7.59 (m, 4H), 7.45 (m, 4H); LC-MS calculated for C27H18C1N7O3S (M+H) 556.1, found 555.9.

Reference： [1]Patent: WO2007/120454,2007,A1 .Location in patent: Page/Page column 83

13
[ 954146-74-8 ]
[ 32111-21-0 ]
N-{3-[1-(4-chloro-phenyl)-6-oxo-2-(4-pyrazin-2-yl-phenyl)-1,6-dihydro-purin-9-yl]-phenyl}-methanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 20℃; for 18h;	Example 58; N- f 3-[" 1 -(4-Chloro-phenvU-6-oxo-2-( 4-pyrazin-2-yl-phenylV 1.6-dihvdro-purin-9-yll-phenyl - methane sulfonamide; [00193] A solution of N-(3-{l-(4-chloro-phenyl)-6-oxo-2-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]-l,6-dihydro-purin-9-yl}-phenyl)-methane sulfonamide (preparaed as described in example 26, 0.5 g, 0.809 mmol) in N,N-dimethylformamide (20 <n="85"/>mL) is degassed with argon for 0.5 h. Then <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.25 g, 1.21 tnmol), cesium carbonate (0.527 g, 1.61 mmol), Pd(dppf)2Cl2 (0.059 g, 0.08 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is stirred at rt for 18 h. The reaction mixture is poured into water and extracted with ethyl acetate (3 *). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography to afford N-{3-[l-(4-chloro-phenyl)-6-oxo-2-(4-pyrazin-2-yl-phenyl)-l ,6- dihydro-purin-9-yl]-phenyl}-methane sulfonamide. 1H NMR (DMSOd6, 400 MHz) delta 9.25 (s, IH), 8.69 (m, IH), 8.62 (m, 2H), 8.03 (m, 2H), 7.74 (s, IH), 7.46-7.56 (m, 9H), 7.25 (m, IH), 3.05 (s, 3H); LC-MS calculated for C28H20ClN7O3S (M+H4) 570.1, found 569.9.

Reference： [1]Patent: WO2007/120454,2007,A1 .Location in patent: Page/Page column 83-84

14
[ 954146-66-8 ]
[ 32111-21-0 ]
3-[1-(4-chloro-phenyl)-6-oxo-2-(4-pyrazin-2-yl-phenyl)-1,6-dihydro-purin-9-yl]-benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 50℃; for 12h;	Example 59; 3-fl-f4-Chloro-phenyl')-6-oxo-2-('4-pyrazin-2-yl-phenv?-.6-dihvdro-purin-9-yll-benzene sulfonamide; [00194] A solution of 3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-l-yl}-benzene sulfonamide (prepared as described in example 25, 0.500 g, 0.82 mmol) in N,N- dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.250 g, 1.24 mmol), cesium carbonate (0.530 g, 1.65 mmol), Pd(dppf)2Cl2 (0.06 g, 0.08 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is then heated at 50 0C for 12 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3*). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and' purified by column chromatography over silica gel (60 - 120 mesh) to afford 3-[l-(4-chloro-phenyl)-6-oxo-2-(4-pyrazin-2-yl-phenyl)-l,6-dihydro-purin- 9-yl]-benzene sulfonamide. 1H NMR (DMSO-dbeta, 400 MHz) delta 9.24 (m, IH), 8.69 (m, IH), <n="86"/>8.63 (m, IH), 8.30 (m, IH), 8.02-8.08 (m, 2H), 7.94 (m, IH), 7.82 (m, IH), 7.43-7.58 (m, 8H), 7.15 (br, 2H); LC-MS calculated for C27H18ClN7O3S (MH-H+) 556.1, found 555.9.

Reference： [1]Patent: WO2007/120454,2007,A1 .Location in patent: Page/Page column 84-85

15
1'-(piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2(1H)-one bis-hydrochloride [ No CAS ]
[ 32111-21-0 ]
1'-(1-(pyrazin-2-yl)piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2'-dicyclohexylphosphanyl-biphenyl-2-ylamine; sodium t-butanolate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; In 1,4-dioxane; at 80℃; for 16h;	Pd2(dba)3 -CHCl3 (5 mg, 0.5 mol %), 2'-(dicyclohexylphosphino)biphenyl-2-amine (8 mg, 2 mol %) and sodium tert-butoxide (13 mg, 0.14 mmol) were weighed in air and transferred into flask, followed by dioxane (750 muL), 1 '-(piperidin-4- yl)spiro[benzo[d][l,3]oxazine-4,4'-piperidin]-2(lH)-one bis-hydrochloride (compound no. 49) (37 mg, 0.10 mmol) and <strong>[32111-21-0]iodopyrazine</strong> (viia). (20.6 mg, 0.10 mmol). The flask was flushed with nitrogen and stirred at 800C for 16 hours. The reaction mixture was diluted with methanol (500 muL), filtered (Whatman 0.45 mum PTFE) and subjected to reverse-phase <n="52"/>HPLC purification (2-25% CH3CN gradient [w/ 0.1% TFA (aq)] over 10 minutes, 1.0 mL injected, 35 mL/min) to provide l'-(l-(pyrazin-2-yl)piperidin-4- yl)spiro[benzo[d][l,3]oxazine-4,4'-pirhoeridin]-2(lH)-one (compound no. 74). LC/MS m/z 380.2 [M+H]+, retention time 1.35 min (RP-Cl 8, 10-99% CH3CN/0.05% TFA).

Reference： [1]Patent: WO2008/21375,2008,A2 .Location in patent: Page/Page column 50-51

16
[ 290-37-9 ]
[ 10199-00-5 ]
[ 32111-21-0 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 6602 - 6605

17
[ 201230-82-2 ]
[ 5680-79-5 ]
[ 32111-21-0 ]
[ 117904-01-5 ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 10372 - 10378

18
[ 201230-82-2 ]
[ 2491-20-5 ]
[ 32111-21-0 ]
[ 73058-31-8 ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 10372 - 10378

19
[ 201230-82-2 ]
[ 32111-21-0 ]
[ 75-64-9 ]
[ 121885-10-7 ]

Reference： [1]Tetrahedron,2007,vol. 63,p. 10372 - 10378

20
[ 110-91-8 ]
[ 201230-82-2 ]
[ 32111-21-0 ]
[ 23698-19-3 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 3678 - 3681
[2]Tetrahedron,2007,vol. 63,p. 10372 - 10378

21
[ 552845-85-9 ]
[ 32111-21-0 ]
[ 552845-86-0 ]

Yield	Reaction Conditions	Operation in experiment
59%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2.5h;Heating / reflux;	2- (5- [1, 3] Dioxolan-2-yl-2, 4-dimethoxy-phenyl)-4, 4,5, 5-tetramethyl- [1, 3,2] dioxaborolane (Ex-12B, 2.22 g, 6.60 mmol, containing borolane impurity) was dissolved in DME (60 mL) and <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.59 mL, 6.0 mmol) was added. 2M aqueous NA2CO3 (17.8 ML, 35.6 mmol) was added and the mixture was purged with nitrogen for 20 min. Tetrakis (triphenylphosphine) palladium (0) (0.69 g, 0.60 mmol) was added and the mixture was heated at reflux for 2.5 h. After cooling, water (50 mL) was added and the mixture was extracted with CH2CI2 (2X30 mL). The organic phase was washed with brine (1X20 ML), dried over sodium sulfate, filtered, and concentrated. Purification of the resulting yellow-orange solids via silica chromatography (50-80% EtOAc/hexanes) provided 1.02 g OF 2- (5- [1, 3] dioxolan-2- yl-2, 4-dimethoxy-phenyl)-pyrazine as a yellow solid (59% YIELD).'H-NMR (CDCIS) 8 9.10 (d, J = 2 Hz, IH), 8.61 (m, 1H), 8.39 (d, J = 3 Hz, I H), 8.07 (s, I H), 6.57 (s, IH), 6.14 (s, 1H), 4.13-4. 18 (m, 2H), 4.01-4. 05 (m, 2H), 3.95 (s, 3H), 3.93 (s, 3H).

Reference： [1]Patent: WO2004/56727,2004,A2 .Location in patent: Page 74

22
[ 406479-74-1 ]
[ 32111-21-0 ]
2-(3-pyrazinyl-prop-2-ynyloxy)-5-chloro-3-methoxypyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With tetrabutyl ammonium fluoride;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; 1,4-dioxane; at 20 - 50℃; for 3h;	4.4 ml of tetrabutylammonium fluoride (1M solution in THF) are added to a solution of 450 mg (2.18 mmol) of <strong>[32111-21-0]iodopyrazine</strong>, 647 mg (3.28 mmol) of 5-chloro-3-methoxy-2-(prop-2-ynyloxy)-pyridine (Example P7), 83 mg (0.44 mmol) of copper(l) iodide and 153 mg (0.22 mmol) of bis(triphenylphosphine)palladium dichloride (Pd(PPh3)2CI2) in 14 ml of dioxane. The reaction mixture is stirred for 3 hours at 50C under an argon atmosphere and is then allowed to cool to 20C. The solvent is removed under reduced pressure and the crude product obtained is purified by means of flash chromatography (eluant: ethyl acetate/petroleum ether 1/2). The desired title compound is obtained as a brown solid having a melting point of 142C in a yield of 510 mg (84 % of theory). Rf = 0.50 in ethyl acetate/petroleum ether 1/1;1H NMR (CDCI3): delta(ppm)= 3.89 (s, 3H); 5.29 (s, 2H); 7.08 (d, J=2.2 Hz, 1H); 7.71 (d, J=2.2 Hz, 1H); 8.48 (d, J=2.5 Hz, 1H); 8.52 (dxd, J=1.3 and 2.5 Hz, 1H); 8.66 (d, J=1.3 Hz, 1H).

Reference： [1]Patent: WO2003/104206,2003,A2 .Location in patent: Page 45

23
[ 497242-89-4 ]
[ 32111-21-0 ]
3-(4-fluoro-2-methoxy-phenoxy)-prop-1-ynyl-pyrazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With tetrabutyl ammonium fluoride;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In 1,4-dioxane; at 20 - 50℃; for 3h;	4.90 ml of tetrabutylammonium fluoride (1M solution in THF) are added to a solution of 500 mg (2.43 mmol) of <strong>[32111-21-0]iodopyrazine</strong>, 655 mg (3.64 mmol) of 4-fluoro-2-methoxy-1-prop-2-ynyloxy-benzene, 92 mg (0.48 mmol) of copper(l) iodide and 170 mg (0.24 mmol) ofbis(triphenylphosphine)palladium dichloride (Pd(PPh3)2CI2) in 16 ml of dioxane. The reactionmixture is stirred for 3 hours at 50C under an argon atmosphere and is then allowed to coolto 20C. The solvent is removed under reduced pressure and the crude product obtained ispurified by means of flash chromatography (eluant: ethyl acetate/petroleum ether 1/2). Thedesired title compound is obtained as a beige solid having a melting point of 88C in a yieldof 412 mg (66 % of theory).Rf = 0.28 in ethyl acetate/petroleum ether 1/2;1H NMR (CDCI3): delta(ppm)= 3.87 (s, 3H); 4.98 (s, 2H); 6.56-6.69 (m, 2H); 7.04 (dxd, J=5.6 and8.8 Hz, 1H); 8.48 (d, J=2.5 Hz, 1H); 8.52 (dxd, J=1.3 and 2.5 Hz, 1H); 8.62 (d, J=1.3 Hz,1H).

Reference： [1]Patent: WO2003/104206,2003,A2 .Location in patent: Page 45

24
[ 643085-51-2 ]
[ 32111-21-0 ]
N-[5-chloro-7-(pyrazin-2-ylethynyl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With diisopropylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In ethyl acetate; at -20℃;	A solution of N- (5-chloro-7-ethynyl-1, 3-benzodioxol-4-yl)-6-methoxy-7- (3- morpholin-4-ylpropoxy) quinazolin-4-amine (0.12g, 0. 24mmol), 3-<strong>[32111-21-0]iodopyrazine</strong> (O. lg, 0. 48mmol) and diisopropylamine (0. 066ml, 0. 48mmol) in ethyl acetate (3ml) was cooled to- 20 C under a nitrogen atmosphere. To this was added copper (I) iodide (0.014g, 0.072mmol) and bis (triphenylphospine) palladium (It) chloride (0.034g, 0. 048mmol). The reaction mixture was allowed to warm to ambient temperature and then stirred overnight. The mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography on silica eluting with a mixture of 0-10% methanol in dichloromethane to give the product as a light yellow solid (0.052g, 38%). NMR Spectrum: (DMSOd6) 1.99 (t, 2H), 2.40 (brs, 4H), 2.50 (t, 2H) partially obscured by DMSO peak, 3.59 (s, 4H), 3.97 (s, 3H), 4.23 (t, 2H), 6.27 (s, 2H), 7.19 (s, 1H), 7.35 (s, 1H), 7.89 (s, 1H), 8.42 (s, 1H), 8.74 (s, 1H), 8.78 (s, 1H), 8.96 (s, 1H), 9.66 (s, 1H). Mass Spectrum: M+H+ 575 and M+H-573.

Reference： [1]Patent: WO2004/4732,2004,A1 .Location in patent: Page/Page column 118-119

25
[ 905856-76-0 ]
[ 32111-21-0 ]
[ 905856-83-9 ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium carbonate;palladium diacetate; trifuran-2-yl-phosphane; In 1,2-dimethoxyethane; water; at 80℃; for 0.75h;	Example 9 A flask was charged with pinacol borobate (383.0 mg, 1.0 mmol), iodopyrazole (226.6 mg, 1.1 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), TFP (46.4 mg, 0.2 mmol), K2CO3 (690.0 mg, 5 mmol), water (3 mL) and DME (2 mL). After 3 vacuum/argon cycles, the resulting mixture was heated to 80 C. 45 min later, HPLC revealed that all boronate disappeared. The area ratio of C-H, coupling product and dimer was about 3.3:85.3:11.4 on HPLC. After the reaction mixture was cooled down to room temperature, EtOAc (5 mL) was added. The aqueous layer was separated and extracted with EtOAc (2*10 mL). The combined organic extracts were washed with brine (10 mL), dried over Na2SO4, and concentrated in vacuo. The crude product was purified via silica gel chromatography to afford the indole (0.27 g, 81%). 1H NMR (300 HMz, CDCl3) delta 8.77 (2H, bs), 8.60 (1H, s), 8.16 (1H, s), 7.82-7.76 (2H, m), 3.96 (3H, s), 3.78 (3H, s), 3.20 (1H, m), 2.08-1.92 (6H, m), 1.72-1.69 (2H, m); 13C NMR (100 HMz, CDCl3) delta 168.0, 147.4, 146.6, 144.4, 143.2, 138.0, 135.3, 129.0, 124.2, 120.5, 120.3, 120.0, 112.4, 52.0, 37.3, 33.6, 31.3, 26.5.

Reference： [1]Patent: US2006/183752,2006,A1 .Location in patent: Page/Page column 18

26
[ 34616-29-0 ]
[ 32111-21-0 ]
[ 125060-63-1 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; diisopropylamine; lithium diisopropyl amide; In tetrahydrofuran; hexane; dichloromethane; water;	2. 1-Methyl-3-carbomethoxy-3-(2-pyrazinyl)pyrrolidine A solution of lithium diisopropylamide in anhydrous THF was prepared by addition of n-butyllithium (7.9 ml of a 1.6M solution in hexane, 12.64 mmol) to a solution of diisopropylamine (1.4 g, 13.9 mmol) in THF (200 ml), at -78 C. The solution was stirred for 0.5 h before adding dropwise to a stirred solution of <strong>[34616-29-0]1-methyl-3-carbomethoxypyrrolidine</strong> (1.5 g, 10.5 mmol) in THF (200 ml), at -78 C. After 1 h, a solution of 2-iodopyrazine (2.73 g, 13.3 mmol) in THF (10 ml) was added dropwise, at -78 C., stirred for 0.25 h, warmed to room temperature, and stirred for a further 16 h. Water (25 ml) and dichloromethane (150 ml) were added, stirred for 0.25 h before separating the aqueous and extracting into dichloromethane (3*100 ml). The combined extracts were dried (Na2 SO4), concentrated under vacuum, and the residue purified by silica-gel chromatography using dichloromethane/methanol (92:8) as eluant. The title pyrazine was obtained as an orange oil (0.36 g) m/e 222 (M+); δ(360 MHz, CDCl3) 2.38 (3H, s, N--Me); 2.43-2.51 (1H, m, CH of CH2); 2.66-2.92 (3H, m, CH of CH2 and CH2 --N); 3.15 (1H, d, J=9.7 Hz, CH of CH2 --N) 3.33 (1H, d, J=9.7 Hz, CH of CH2 --N); 3.72 (3H, s, CO2 Me); 8.44 (1H, d, J=1.5 Hz, pyrazine-H); 8.49 (1H, d, J=2 Hz, pyrazine-H), 8.64 (1H, dd, J=1.5 and 2 Hz, pyrazine-H).

Reference： [1]Patent: US5260293,1993,A

27
[ 925221-77-8 ]
[ 32111-21-0 ]
[ 925220-99-1 ]

Yield	Reaction Conditions	Operation in experiment
47%	With potassium phosphate;copper(l) iodide; rac-diaminocyclohexane; In 1,4-dioxane; at 140℃; for 0.5h;microwave irradiation;	Example 42; Synthesis of Compound 76; Compound a from the synthesis of compound 74 (255 mg) was placed in an oven dried microwave reaction vial with CuI (53.3 mg) and K3PO4 (233.4 mg) and purged with N2. To this mixture was added <strong>[32111-21-0]iodopyrazine</strong> b and the vial purged again with N2 followed by addition of 1,2-cyclohexanediamine (62.8 mg) in 2.6 ml dioxane and N2 was bubbled into the solution for 10 min and the vial crimped. The reaction vial was placed in the microwave for 30 min. at 140 C. The reaction went to half completion and was worked up by filtering off the non-product solids, concentrating under vacuum, and purifying by flash to give 139 mg compound c (47% yield). Compound c was dissolved in 3 ml 1.0 M TBAF in THF and heated to 60 C. overnight. The reaction was completed by LCMS and was diluted with H2O, extracted with EtOAc, washed with brine, dried over MgSO4, concentrated under vacuum and purified by SFC to give the final compound 76.

Reference： [1]Patent: US2007/37791,2007,A1 .Location in patent: Page/Page column 72-73

28
[ 32111-21-0 ]
[ 852709-39-8 ]

Yield	Reaction Conditions	Operation in experiment
61%		To a solution of 3-nitrophenol (0.151 g, 0.733 mmol) in DMSO (5 mL) was added NaH (35 mg of a 60% dispersion, 0.88 mmol) at 0 C under Ar atmosphere. After stirring for 30 min, <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.133 mg, 0.953 mmol) was added and mixture heated to 85 C for 4h. To the mixture was added satd. NH4Cl solution (25 mL) and the product extracted with EtOAc (2x25 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated to yield a crude residue which was purified by column chromatography to afford (97 mg, 61% yield) 2-(3-nitrophenoxy)pyrazine as a white solid.

Reference： [1]Patent: WO2006/71940,2006,A2 .Location in patent: Page/Page column 353

29
MeOH-NH₄OH [ No CAS ]
[ 305794-71-2 ]
ammonium chloride [ No CAS ]
[ 32111-21-0 ]
[ 676491-17-1 ]

Yield	Reaction Conditions	Operation in experiment
68%	With n-butyllithium;(Ph3P)4Pd; SiO2; zinc(II) chloride; In tetrahydrofuran; dichloromethane;	Preparation of 4-(1-Phenyl-1-(pyrazin-2-yl)-methylene)-piperidine-1-carboxylic acid tert-butyl ester: To a solution of 4-(1-bromo-1-phenyl-methylene)-piperidine-1-carboxylic acid tert-butyl ester (0.352 g, 1.0 mmol) in 4 mL of dry THF, at -78 C. under Ar, was added n-butyllithium solution (1.6M in hexanes, 0.75 mL, 1.2 mmol) dropwise. After 15 min, a solution of freshly fused ZnCl2 in 1.2 mL of dry THF was added dropwise and then the cooling bath was removed and the reaction mixture was allowed to warm to room temperature. To this mixture was then added <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.119 mL, 1.2 mmol) and (Ph3P)4Pd (0.058 g, 5 mol %) and the reaction vessel was sealed and then heated at 90 C. for 16 h. The cooled mixture was quenched with saturated aqueous NH4Cl and then it was partitioned with EtOAc-water. The organic phase was washed (brine), dried (Na2SO4) and evaporated to give a dark brown gum. Flash chromatography of this material [SiO2/1-2% MeOH-NH4OH (9:1) in CH2Cl2] afforded the title compound (0.237 g, 68%) as a light yellow solid: 1Hnmr (400 MHz, CDCl3) delta 8.58 (m, 1H), 8.42 (d, J=2.5 Hz, 1H), 8.40 (d, J=1.5 Hz, 1H), 7.37-7.16 (m, 5H), 3.51 (m, 4H), 2.44 (app t, 2H), 2.40 (app t, 2H), 1.49 (s, 9H). LCMS: m/e 352 (M+H)+.

Reference： [1]Patent: US2004/186292,2004,A1

30
[ 936250-22-5 ]
[ 32111-21-0 ]
[ 13481-05-5 ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 5712 - 5716

31
[ 1826-11-5 ]
[ 32111-21-0 ]
[ 1000029-21-9 ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 7996 - 8000

32
[ 111-86-4 ]
[ 32111-21-0 ]
N-(1-octyl)-aminopyrazine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 6586 - 6596

33
[ 305794-71-2 ]
[ 32111-21-0 ]
[ 676491-17-1 ]

Yield	Reaction Conditions	Operation in experiment
68%		[0580] To a solution of 4-(1-bromo-1-phenyl-methylene)-piperidine-1-carboxylic acid tert-butyl ester (0.352 g, 1.0 mmol) in 4 mL of dry THF, at -78 C. under Ar, was added n-butyllithium solution (1.6M in hexanes, 0.75 mL, 1.2 mmol) dropwise. After 15 min, a solution of freshly fused ZnCl2 in 1.2 mL of dry THF was added dropwise and then the cooling bath was removed and the reaction mixture was allowed to warm to room temperature. To this mixture was then added <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.119 mL, 1.2 mmol) and (Ph3P)4Pd (0.058 g, 5 mol %) and the reaction vessel was sealed and then heated at 90 C. for 16 h. The cooled mixture was quenched with saturated aqueous NH4Cl and then it was partitioned with EtOAc-water. The organic phase was washed (brine), dried (Na2SO4) and evaporated to give a dark brown gum. Flash chromatography of this material [SiO2/1-2% MeOH-NH4OH (9:1) in CH2Cl2] afforded the title compound (0.237 g, 68%) as a light yellow solid: [0581] 1Hnmr (400 MHz, CDCl3) delta 8.58 (m, 1H), 8.42 (d, J=2.5 Hz, 1H), 8.40 (d, J=1.5 Hz, 1H), 7.37-7.16 (m, 5H), 3.51 (m, 4H), 2.44 (app t, 2H), 2.40 (app t, 2H), 1.49 (s, 9H). [0582] LCMS: m/e 352 (M+H)+.

Reference： [1]Patent: US2004/63744,2004,A1 .Location in patent: Page/Page column 107-108

34
2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic acid [ No CAS ]
[ 32111-21-0 ]
[ 1146395-31-4 ]

Yield	Reaction Conditions	Operation in experiment
32%	With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; at 150℃; for 0.666667h;microwave irradiation;	To a solution of 0.40 g (1.53 mmol) of [4-(4,4,5,5-tetramethyl- 1,3,2- dioxaborolan-2-yl)phenyl]acetic acid in 4.0 ml of dioxane was added 0.18 mL (1.73 mmol) of 2- <strong>[32111-21-0]iodopyrazine</strong>, 10.3 mg (0.037 mmol) of tricyclohexylphosphine, 13.9 mg (0.015 mmol) of Pd2(dba)3, and 2.0 ml (1.27 M, 2.59 mmol) of aqueous potassium phosphate solution. The resulting suspension was degassed for 10 mins. After 30 min in the microwave at 1500C, the reaction mixture was cooled, acidified with IN HCl, extracted with ethyl acetate, and washed with brine. The organic layer was dried over Na2Stheta4, filtered and concentrated in vacuo. Purification by preparative HPLC (5 -> 95% CH3CN/H2O over 15min, 0.05% added TFA, C 18) afforded 0.10 g (32%) of (4-pyrazin-2-ylphenyl)acetic acid. 1H NMR (CD3OD, 400 MHz) 9.1 (s, IH); 8.66 (t, J= 1.74 Hz, IH); 8.51 (d, J= 2.57 Hz, IH); 8.04 (d, J= 8.15 Hz, 2H); 7.46 (d, J= 8.15 Hz, 2H); 3.70 (s, 2H). ES-MS M+l = 215.1.

Reference： [1]Patent: WO2009/54984,2009,A1 .Location in patent: Page/Page column 40

35
[ 767-00-0 ]
[ 32111-21-0 ]
[ 866042-79-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	With N,N-dimethylglycine hydrochoride; caesium carbonate;copper(l) iodide; In 1,4-dioxane; at 90℃; for 138h;	2-lodopyrazine (2.00 g, 9.42 mmol), copper(l) iodide (366 mg, 1.88 mmol), cesium carbonate (6.14 g, 18.84 mmol), 4-hydroxybenzonithle (1.68 g, 14.13 mmol) and N,N-dimethylglycine hydrochloride (398 mg, 2.83 mmol) were dried and placed under nitrogen and then degassed 1 ,4-dioxane (25.0 ml_) was added. The whole mixture was heated at 90 0C for 138 hours. The cooled mixture was partitioned between ethyl acetate (50 ml_) and water (50 ml_). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 x 50 ml_). The organic layers were combined and washed with brine (50 ml_) and dried with Na2SO4 and concentrated in vacuo. The crude solid was placed on a silica gel column and purified (EtOAc/Hex 1 :8) to give the product as an off white solid (1.61 g, 87%). 1H NMR (300 MHz, CDCL3) <5(ppm): 7.31 (2H, d, J = 9.1 Hz), 7.74 (2H, d, J = 9.1 Hz), 8.14 (1 H, dd, J = 2.4, 1.4 Hz), 8.37 (1 H, d, J = 2.4 Hz), 8.51 (1 H, s). 13C NMR (75 MHz, CDCL3) d(ppm): 109.0, 118.5, 122.0 (CH), 134.1 (CH), 136.4 (CH), 139.8 (CH), 141.1 (CH), 156.7, 159.1. MS (FAB+): 198 (MH+). HRMS for CnH7N3O (MH+): calculated: 198.0667; found 198.0661.
87%	With caesium carbonate;copper(l) iodide; N,N-dimethylglycine hydrochoride; In 1,4-dioxane; at 90℃; for 138h;Inert atmosphere;	2-Iodopyrazine (2.00 g, 9.42 mmol), copper(I) iodide (366 mg, 1.88 mmol), cesium carbonate (6.14 g, 18.84 mmol), 4-hydroxybenzonitrile (1.68 g, 14.13 mmol) and N,N-dimethylglycine hydrochloride (398 mg, 2.83 mmol) were dried and placed under nitrogen and then degassed 1,4-dioxane (25.0 mL) was added. The whole mixture was heated at 90 C. for 138 hours. The cooled mixture was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The organic layers were combined and washed with brine (50 mL) and dried with Na2SO4 and concentrated in vacuo. The crude solid was placed on a silica gel column and purified (EtOAc/Hex 1:8) to give the product as an off white solid (1.61 g, 87%). 1H NMR (300 MHz, CDCL3) delta(ppm): 7.31 (2H, d, J=9.1 Hz), 7.74 (2H, d, J=9.1 Hz), 8.14 (1H, dd, J=2.4, 1.4 Hz), 8.37 (1H, d, J=2.4 Hz), 8.51 (1H, s). 13C NMR (75 MHz, CDCL3) delta(ppm): 109.0, 118.5, 122.0 (CH), 134.1 (CH), 136.4 (CH), 139.8 (CH), 141.1 (CH), 156.7, 159.1. MS (FAB+): 198 (MH+). HRMS for C11H7N3O (MH+): calculated: 198.0667; found 198.0661.

Reference： [1]Patent: WO2009/41972,2009,A1 .Location in patent: Page/Page column 30-31
[2]Patent: US2010/261673,2010,A1 .Location in patent: Page/Page column 12-13

36
[ 7299-51-6 ]
[ 32111-21-0 ]
ethyl 3-(2-pyrazinyl)-2-propynoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With triethylamine; zinc dibromide;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 20℃; for 16h;	To a dry solution of zinc bromide (6.49 g, 28.8 mmol) in tetrahydrofuran (60 mL) was added triethylamine (16 mL, 115.2 mmol), <strong>[32111-21-0]iodopyrazine</strong> (4.95 g, 24 mmol), ethyl proprionate (3.66 mL, 36 mmol) and tetrakis(triphenylphosphine) palladium (832 mg, 0.72 mmol). The reaction mixture was allowed to stir at ambient temperature for 16 h, diluted with diethyl ether, washed with saturated aqueous ammonium chloride and saturated aqueous sodium chloride, dried with anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel column chromatography (40% ethyl acetate in heptane) to yield the title compound as an orange oil (2.19 g, 52% yield). LCMS (m/z): 176.97 (M+).

Reference： [1]Patent: US2009/247547,2009,A1 .Location in patent: Page/Page column 52

37
[ 446284-32-8 ]
[ 32111-21-0 ]
[ 676491-50-2 ]

Yield	Reaction Conditions	Operation in experiment
60%		To a solution of <strong>[32111-21-0]iodopyrazine</strong> 1 (45.8 g, 0.222 mol) in tetrahydrofuran (THF) (460 ml) at -18C, BuMgCl (2 M in THF, 108 ml, 216 mmol) was added dropwise via an addition funnel over 20 minutes. The internal temperature of the resulting suspension was raised to -1O0C after addition. The mixture was stirred for another 40 minutes during which time the internal temperature dropped to -180C. Then, ZnCl2 (0.5 M in THF, 220 mmol) was added via addition funnel over 15 minutes. The NaCl-ice bath was removed after addition and the mixture was warmed up to room temperature over 2 hours and was stirred at room temperature for another 0.5 hours. Chloroazaindole 2 (12.95 g, 71 mmol) and PdCl2(dppf)2 (5.8 g, 7.1 mmol) were added into the mixture and mixture heated at 58C for 6 hours, then stirred at room temperature overnight. Analysis by HPLC showed >20:l ratio of product to starting material.The reaction was quenched with NH4Cl (36 N aqueous, 25 ml) and the resulting inorganic salt was filtered off and washed with THF. The filtrate was concentrated to about 200 ml and IL of dichloromethane was added. The solution was washed with brine (3x500 ml) and dried (Na2SO4). The solution was concentrated and the residue was absorbed onto silica gel (25 g), then put on top of a silica gel (105 g) column and eluted with hexanes and EtOAc(hexanes:EtOAc=3:l to 0:1). Removal of the solvent gave crude coupled azaindole 3 which was then heated in refluxing EtOAc (350 ml) for about 0.5 hours. After an insoluble sparkling dark red solid was filtered off, and EtOAc was removed, a brown solid (14.86 g) was obtained, which was then dissolved in a refluxing solution of hexanes (40 ml) and EtOAc (120 ml). The resulting solution was cooled to room temperature and the product isolated by filtration to give a brown solid 3 (9.56 g, >99% pure by HPLC, 60% yield).1H NMR (DMSO-d6, 300 MHz) (delta, ppm): 4.02(s, 3H), 6.63-6.65(m, IH), 7.56(t, / = 2.7Hz, IH), 8.04(s, IH), 8.64(d, / = 2.7Hz, IH), 8.74-8.75(m, IH), 9.62(d, / = 1.5Hz, IH), 11.78 (br, s, IH); LCMS: m/e 227 (M+H)+.Analysis by ICP-MS showed <1 ppm tin, 1669 ppm iron, 83ppm zinc.

Reference： [1]Patent: WO2009/114313,2009,A2 .Location in patent: Page/Page column 15-16
[2]Organic Process Research and Development,2013,vol. 17,p. 907 - 914

38
[ 563-80-4 ]
[ 32111-21-0 ]
[ 1206625-50-4 ]

Yield	Reaction Conditions	Operation in experiment
60%		<strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (10 g, 48.55 mmol) in dry diethyl ether (100 ml) was cooled to -78C. n-BuLi (2.5M in hexanes) (20.39 ml of 2.5 M, 50.98 mmol) was added dropwise over 10 minutes. A brown heterogeneous mixture was produced and it was stirred at -78C for 10 minutes, then warmed to -5O0C and stirred for an additional 60 minutes. The mixture was then re-cooled to - 78C and 3-methylbutan-2-one (5.227 g, 6.493 ml, 60.69 mmol) was added. The mixture was stirred for 10 minutes. Further diethyl ether (10ml) was added. The mixture was then allowed to warm to ambient. A saturated ammonium chloride aqueous solution (40ml) and ethyl acetate (100ml) were added and the mixture stirred for 5 minutes. The organic layer was separated and the aqueous extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate, filtered and concentrated. The crude was purified on silica-gel, eluting with 40% ethyl acetate/petrol to afford the title compound as a pale yellow oil (4.74g, 60%). 1H NMR (CDCl3) 0.75 (3H, d), 0.99-1.01 (3H, d), 1.58 (3H5 s), 2.05-2.09 (IH, m), 4.10-4.40 (IH, m), 8.51 -8.52 (2H, m), 8.73 (I H, s).

Reference： [1]Patent: WO2010/11772,2010,A2 .Location in patent: Page/Page column 113; 114

39
[ 32111-21-0 ]
[ 590-86-3 ]
[ 1179193-42-0 ]

Yield	Reaction Conditions	Operation in experiment
68%		To a solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (10.0 g, 48.5 mmol) in diethyl ether at -50 0C was added dropwise H-BuLi (2.5 M in hexanes, 25 mL, 60.7 mmol), immediately followed by addition of isovaleraldehyde (8.13 mL, 6.48 g, 75 mmol) over 5 minutes. The mixture was allowed to reach room temperature and was added to a saturated NH4Cl solution. The aqueous phase was extracted with TBME (3 x 100 mL) and the combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. The resulting oil was filtered over a plug of silica to afford 3-methyl-l-(pyrazin-2-yl)butan-l-ol as a yellow-brownish oil (5.5g; 68%) .

Reference： [1]Patent: WO2010/11772,2010,A2 .Location in patent: Page/Page column 112

40
[ 1046337-92-1 ]
[ 32111-21-0 ]
[ 1227746-56-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In acetonitrile; at 90℃; for 13h;	General procedure: A mixture of tertiary propargylic alcohol 5 (0.13 mmol), (hetero)aryl halide (1.5 equiv), Pd(PPh3)4 (5 mol %), and K2CO3 (2.5 equiv) in CH3CN (1 mL) was heated at 90 C for 13 h. The reaction mixture was concentrated under reduced pressure to give the crude residue, which was diluted with ethyl acetate and washed with water. The organic layer was dried over MgSO4 and concentrated in vacuo to give a crude mixture, which was purified by silica gel column chromatography (hexane/ethyl acetate/dichloromethane) to afford the indolizinone 7.

Reference： [1]Organic Letters,2010,vol. 12,p. 2500 - 2503
[2]Tetrahedron,2012,vol. 68,p. 5464 - 5480

41
[ 1239879-77-6 ]
[ 32111-21-0 ]
[ 1239878-32-0 ]

Yield	Reaction Conditions	Operation in experiment
74%		To a solution of nBuMgCl (0.17 mmol, 0.33 eq) in dry THF (4 mL) was added nBuLi (0.55 mmol, 1.1 eq) at -20 C. and the reaction mixture was stirred at -20 C. for 30 minutes. 2-Iodopyrazine (103 mg, 0.50 mmol, 1.0 eq) was added at -20 C. and the reaction mixture was stirred at -10 C. for 2 hours. The reaction mixture was cooled to -20 C. and a solution of intermediate I-31 (135 mg, 0.50 mmol, 1.0 eq) in THF (1 mL) was added. The reaction mixture was stirred at -20 C. for 1 hour and then at room temperature until TLC analysis indicated complete disappearance of the starting material. The reaction mixture was quenched by adding saturated aqueous solution of ammonium chloride and extracted with dichloromethane. The combined organic layers were dried over anhydrous Na2SO4, the solids were removed by filtration and the filtrate was concentrated by evaporation. The crude reaction product was purified by preparative TLC to give compound 120 (130 mg, 74%). 1H-NMR (400 MHZ, CDCl3): delta 8.63 (d, 1H, J=0.8 Hz), 8.49 (dd, 1H, J1=0.8 Hz, J2=2.8 Hz), 8.44 (d, 1H, J=2.8 Hz), 7.68 (s, 1H), 7.25 (dd, 1H, J1=1.2 Hz, J2=8.8 Hz), 7.20 (d, 1H, J=8.8 Hz), 5.98 (s, 1H), 5.30 (s, 1H), 4.184.20 (m, 2H), 3.183.21 (m, 2H), 2.882.91 (m, 1H), 2.542.61 (m, 4H), 2.082.14 (m, 2H), 1.861.91 (m, 2H), 1.611.74 (m, 2H). MS (ESI): m/z 350 (M+H+).

Reference： [1]Patent: US2010/204214,2010,A1 .Location in patent: Page/Page column 72

42
[ 1239883-35-2 ]
[ 32111-21-0 ]
[ 1239879-50-5 ]

Yield	Reaction Conditions	Operation in experiment
21%	With sodium hydroxide;palladium bis[bis(diphenylphosphino)ferrocene] dichloride; In N,N-dimethyl-formamide; at 100℃; for 1h;Inert atmosphere; Microwave irradiation;	I-111 (0.10 g, 0.31 mmol), Pd(dppf)2Cl2 (23 mg, 0.03 mmol), NaOH (38 mg, 0.94 mmol) and <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (64 mg, 0.31 mmol) were dissolved in DMF (1 mL) in a microwave tube that was filled with argon. The reaction mixture was stirred at 100 C. for 1 h under microwave irradiation. The reaction mixture was diluted with ethyl acetate and filtered through a short plug of Celite. The filtrate was washed with brine and the combined organic layers were dried over Na2SO4, the solids were filtered and the filtrate was concentrated. The crude reaction mixture was purified by preparative TLC to give compound 236 (0.018 g, 21%). 1H NMR (400 MHz, CDCl3): delta 9.08 (d, 2H). 8.98 (d, 1H, J=2.0 Hz), 8.67 (m, 1H), 8.540 (m, 2H), 4.53 (m, 2H), 3.30 (m, 2H), 2.85-2.94 (m, 1H), 2.68 (m, 4H), 2.12-2.16 (m, 2H), 1.86-1.98 (m, 2H), 1.62-1.78 (m, 2H). MS (ESI): m/z 321 (M+1)+.

Reference： [1]Patent: US2010/204214,2010,A1 .Location in patent: Page/Page column 96

43
[ 827614-64-2 ]
[ 32111-21-0 ]
[ 827588-90-9 ]

Yield	Reaction Conditions	Operation in experiment
43.702%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 100℃; for 1h;Sealed tube; Microwave irradiation;	A microwave vial with stirrer bar was charged with 2-aminopyridine-5-boronic acid pinacol ester(0.95g, 4.3mmol) <strong>[32111-21-0]iodopyrazine</strong> (777mg, 3.77mmol), sodium carbonate (1 .20g, 11 .32mmol) Toluene(5mL) Water (5mL) Ethanol (5mL) and degassed for 10 mins.Tetrakis(triphenylphosphine)palladium(0) (436mg, 0.38mmol) was then added and the vial sealed then irradiated at 100C for 1 hr. Analysis showed completion so the reaction mixture was concentrated to dryness, then the residue was suspended in DCM and 1 M aqueous HCI was then added. The phases were separated and the aqueous phase was basified with 10% aqueous NaOH until pH-12, The aqueous layer was re-extracted with EtOAc several times, dried over sodiumsulphate, filtered and concentrated. The resulting solid was triturated with diethyl ether and then filtered giving 5-pyrazin-2-ylpyridin-2-amine (355mg, 1 .6Smmol, 43.702% yield) as a pink powder.MS Method 2: RT 0.45 mi ES mlz 172.9 [M+H]1H NMR (400MHz, DMSO) O/ppm: 9.08 (5, 1H), 8.71-8.73 (d, J=1.9Hz, 1H), 8.58-8.6 (m, 1H), 8.45-8.47 (d, J=2.5Hz, 1H), 8.10-8.14 (dd, J=8.7, 2.5Hz, 1H), 6.54-6.57 (d, J=8.7Hz, 1H), 6.41-6.47 (bs,2H)
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 10h;Inert atmosphere; Sealed tube;	To a sealed tube was added 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)pyridin-2-amine 86-1 (2.2 g, 10 mmol), <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> 86-2 (2.06 g, 10 mmol), Pd(PPh3)4 (577 mg, 0.5 mmol), toluene (70 mL), ethanol (15 mL) and 2M Na2CO3 (15 mL). The reaction mixture was bubbled with nitrogen for 2 minutes and stirred at 90 C for 10 hours. After cooling to room temperature, the solvents were evaporated and the residue was redissolved in dichloromethane (200 ml) and treated with IM HCl aqueous solution (50 mL). The two layers were separated and the aqueous layer was treated with 10% NaOH aqueous solution to adjust the pH to around 13. The resulting suspension was extracted with ethyl acetate (100 mL x 3). The combined organic phases were washed with H2O (50 mL) and brine (50 mL), dried over Na2SO4, and concentrated to give 5-(pyrazin-2-yl)pyridin-2-amine 86-3 as white solid. MS m/z 173.1 (M + 1); 1H NMR 400 MHz (DMSO-J6) delta 9.12(d, IH, J = 1.6 Hz), 8.73(m, IH), 8.60(m, IH), 8.46(d, IH, J = 2.8 Hz), 8.12(dd, IH, /, = 8.8Hz, J2 = 2.4 Hz), 6.55(d, IH, J= 8.8 Hz), 6.46(s, 2H).

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 676 - 680
[2]Patent: WO2016/55790,2016,A1 .Location in patent: Paragraph 00168; 00169
[3]Patent: WO2010/101849,2010,A1 .Location in patent: Page/Page column 54

44
[ 32111-21-0 ]
[ 38521-09-4 ]

Yield	Reaction Conditions	Operation in experiment
78%	With caesium carbonate; thiourea; copper(II) oxide; In dimethyl sulfoxide; at 20 - 110℃;Inert atmosphere;	General procedure: To a stirred solution of aryl halides (2.0 mmol) and thiourea (1.2 equiv) in dry DMSO (2.0 mL) at rt was added nano CuO (5.0 mol %) followed by Cs2CO3 (2.0 equiv) and heated at 110 C for 15 h. The progress of the reaction was monitored by TLC. After the reaction was complete, the reaction mixture was allowed to cool, and a 1:1 mixture of ethyl acetate/water (20 mL) was added. The combined organic extracts were dried with anhydrous Na2SO4. The solvent and volatiles were completely removed under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 9:1) to afford the corresponding coupling product in excellent yields.Recycling of the catalyst:after the reaction was complete, the reaction mixture was allowed to cool, and a 1:1 mixture of ethyl acetate/water (2.0 mL) was added and CuO was removed by centrifugation. After each cycle, the catalyst was recovered by simple centrifugation, washing with deionized water and ethyl acetate and then drying in vacuo. The recovered nano CuO was used directly in the next cycle.Data of representative examples:Dip-tolylsulfane (Table 3, entry 3): yellow oil;1H NMR (200 MHz, CDCl3, TMS): delta = 7.21 (d, 4H, J = 8.0 Hz), 7.06 (d, 4H, J = 8.0 Hz), 2.32 (s, 6H); 13C NMR (50 MHz, CDCl3, TMS): delta = 136.7, 132.81, 131.0, 129.8, 96.1.Table 3, entry 3): yellow oil;1H NMR (200 MHz, CDCl3, TMS): delta = 7.21 (d, 4H, J = 8.0 Hz), 7.06 (d, 4H, J = 8.0 Hz), 2.32 (s, 6H); 13C NMR (50 MHz, CDCl3, TMS): delta = 136.7, 132.81, 131.0, 129.8, 96.1.Bis(4-ethylphenyl)sulfane (Table 3, entry 4): colorless oil; 1HNMR (300 MHz, CDCl3, TMS): delta = 7.21(d, 4H, J = 7.8 Hz), 7.07 (d, 4H, J = 7.8 Hz), 2.62-2.52 (m, 4H), 1.26 (t, 6H, J = 7.8 Hz);13C NMR (75 MHz, CDCl3, TMS): delta = 143.1, 132.7, 131.0, 128.6, 28.3, 15.4; mass (EI): m/z 242 [M]+; Anal. calcd for: (C16H18S) C, 79.29; H, 7.49; S, 13.23; found: C,79.22; H,7.42; S,13.19.Table 3, entry 4): colorless oil; 1HNMR (300 MHz, CDCl3, TMS): delta = 7.21(d, 4H, J = 7.8 Hz), 7.07 (d, 4H, J = 7.8 Hz), 2.62-2.52 (m, 4H), 1.26 (t, 6H, J = 7.8 Hz);13C NMR (75 MHz, CDCl3, TMS): delta = 143.1, 132.7, 131.0, 128.6, 28.3, 15.4; mass (EI): m/z 242 [M]+; Anal. calcd for: (C16H18S) C, 79.29; H, 7.49; S, 13.23; found: C,79.22; H,7.42; S,13.19.Bis(3-nitrophenyl)sulfane (Table 3, entry 7): pale yellow oil; 1H NMR (300 MHz, CDCl3, TMS): delta = 8.19-8.15 (m, 4H), 7.65 (d, 2H, J = 8.3 Hz), 7.55 (t, 2H, J = 8.3 Hz); 13C NMR (75 MHz, CDCl3, TMS): delta = 148.8, 136.7, 130.7, 125.6, 122.7; mass (EI): m/z 276 [M]+; Anal. calcd for: (C12H8N2O4S) C, 52.17; H, 2.92; S, 11.61; N, 10.14; found: C, 52.12; H, 2.86; S, 11.55; N, 10.9.Table 3, entry 7): pale yellow oil; 1H NMR (300 MHz, CDCl3, TMS): delta = 8.19-8.15 (m, 4H), 7.65 (d, 2H, J = 8.3 Hz), 7.55 (t, 2H, J = 8.3 Hz); 13C NMR (75 MHz, CDCl3, TMS): delta = 148.8, 136.7, 130.7, 125.6, 122.7; mass (EI): m/z 276 [M]+; Anal. calcd for: (C12H8N2O4S) C, 52.17; H, 2.92; S, 11.61; N, 10.14; found: C, 52.12; H, 2.86; S, 11.55; N, 10.9.4,4'-Thiodianiline (Table 3, entry 11): brown solid; mp 104-105 C; 1H NMR (300 MHz, CDCl3, TMS): delta = 7.10 (d, 4H, J = 8.68 Hz), 6.52 (d, 4H, J = 8.68 Hz), 3.51 (br s, 4H); 13C NMR (75 MHz, CDCl3, TMS): delta = 145.5, 133.8, 132.6, 124.8, 115.6; mass (EI): m/z 216 [M]+; Anal. calcd for: (C12H12N2S) C, 66.63; H, 5.59; N, 12.95; S, 14.82; Found: C, 66.61; H, 5.58; N, 12.92; S, 14.81.Table 3, entry 11): brown solid; mp 104-105 C; 1H NMR (300 MHz, CDCl3, TMS): delta = 7.10 (d, 4H, J = 8.68 Hz), 6.52 (d, 4H, J = 8.68 Hz), 3.51 (br s, 4H); 13C NMR (75 MHz, CDCl3, TMS): delta = 145.5, 133.8, 132.6, 124.8, 115.6; mass (EI): m/z 216 [M]+; Anal. calcd for: (C12H12N2S) C, 66.63; H, 5.59; N, 12.95; S, 14.82; Found: C, 66.61; H, 5.58; N, 12.92; S, 14.81.Dithiophen-3-ylsulfane (Table 3, entry 15): yellow oil; 1H NMR (300 MHz, CDCl3, TMS): delta = 7.31-7.25 (m, 2H), 7.17-7.11(m, 2H), 6.96-6.94 (m, 2H); 13C NMR (75 MHz, CDCl3, TMS): delta = 129.6, 126.4, 124.7; mass (EI): m/z 197 [M]+; Anal. calcd for: (C8H6S3) C, 48.45; H, 3.05; S, 48.50; found: C,48.42; H,3.02; S,48.47.Table 3, entry 15): yellow oil; 1H NMR (300 MHz, CDCl3, TMS): delta = 7.31-7.25 (m, 2H), 7.17-7.11(m, 2H), 6.96-6.94 (m, 2H); 13C NMR (75 MHz, CDCl3, TMS): delta = 129.6, 126.4, 124.7; mass (EI): m/z 197 [M]+; Anal. calcd for: (C8H6S3) C, 48.45; H, 3.05; S, 48.50; found: C,48.42; H,3.02; S,48.47.Dipyrimidin-5-ylsulfane (Table 3, entry 17): colorless oil; 1H NMR (300 MHz, CDCl3, TMS): delta = 9.15 (s, 2H), 8.74(s, 4H); 13C NMR (75 MHz, CDCl3, TMS): delta = 158.6, 157.7, 129.8; mass (EI): m/z 190 [M]+; Anal. calcd for: (C8H6N4S) C, 50.51; H, 3.18; N, 29.45; S, 16.86; found: C, 50.45; H, 3.13; N, 29.41; S, 16.81.Table 3, entry 17): colorless oil; 1H NMR (300 MHz, CDCl3, TMS): delta = 9.15 (s, 2H), 8.74(s, 4H); 13C NMR (75 MHz, CDCl3, TMS): delta = 158.6, 157.7, 129.8; mass (EI): m/z 190 [M]+; Anal. calcd for: (C8H6N4S) C, 50.51; H, 3.18; N, 29.45; S, 16.86; f...

Reference： [1]Advanced Synthesis and Catalysis,2013,vol. 355,p. 2297 - 2307
[2]Tetrahedron Letters,2011,vol. 52,p. 2679 - 2682
[3]Beilstein Journal of Organic Chemistry,2011,vol. 7,p. 886 - 891

45
[ 32111-21-0 ]
[ 1066-54-2 ]
[ 291763-66-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere;	A mixture of 8a-16a (1.0 equiv), CuI (0.1 equiv) and Pd(PPh3)4 (0.05 equiv) in Et3N and DMF was degassed with Ar. Trimethylsilylacetylene (2.0 equiv) was then added and the solution was stirred for 18 h at room temperature under an Ar atmosphere. TLC analysis showed complete conversion of starting material to a major product. The reaction mixture was then cooled to room temperature, diluted with Et2O, washed twice with satd aq NH4Cl, dried over Na2SO4, filtered, and concentrated in vacuum. The crude product was purified by silica gel column chromatography to yield pure material.
74.4%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; at 20℃; for 48h;Inert atmosphere;	To a solution of 8(5.0g. 24.39mmoi) and 2(2.82g, 26.8mmoi) in 100 mL of Et3N was addedPd(PPh3)4 (1 .4g, I .22mmol) and CuT (C. 46g, 2.44mmol). The reaction mixture was protected byN atmosphere, and was stirred at room temperature for 48 hours. TLC showed the startingmaterial was consumed. The reaction mixture was then concentrated in vacuum. The resultingcrude product was purified by silica gel column chromatography to give product 9(3.2 g, yield:74.4%).

Reference： [1]Carbohydrate Research,2011,vol. 346,p. 1083 - 1092
[2]Inorganic Chemistry,2020,vol. 59,p. 1785 - 1803
[3]Patent: WO2017/117708,2017,A1 .Location in patent: Page/Page column 18; 19
[4]MedChemComm,2019,vol. 10,p. 263 - 267

46
[ 32111-21-0 ]
[ 1258444-09-5 ]

Yield	Reaction Conditions	Operation in experiment
76%	With copper(l) iodide; (1R,2R)-1,2-diaminocyclohexane; water; potassium selenocyanate; caesium carbonate; at 100℃; for 24h;Air atmosphere;	General procedure: Aryl halide (1.0 mmol), CuI (10 mol %), L4 (10 mol %), Cs2CO3 (2.0 equiv) and potassium selenocyanate (1.2 mmol) were charged in a 10 ml round bottom flask with a condenser under air, followed by the addition of water (3.0 mL). The reaction mixture was heated in an oil bath at 100 C and stirred at this temperature for 24 h. The progress of the reaction was monitored by TLC. After the reaction was complete, the reaction mixture was allowed to cool, and treated with ethyl acetate. The combined organic extracts were dried with anhydrous Na2SO4. The solvent and volatiles were completely removed under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 9:1) to afford the corresponding coupling product in excellent yields. All the products were characterized by 1H and 13C NMR, MS and compared with the literature values.

Reference： [1]Synlett,2011,p. 1268 - 1272
[2]Tetrahedron Letters,2011,vol. 52,p. 3978 - 3981

47
[ 10210-17-0 ]
[ 32111-21-0 ]
[ 1322668-34-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	With copper(l) iodide; sodium t-butanolate In N,N-dimethyl-formamide at 70℃; for 21h; Inert atmosphere; chemoselective reaction;

Reference： [1]Maiti, Debabrata [Chemical Communications, 2011, vol. 47, # 29, p. 8340 - 8342]

48
[ 109179-31-9 ]
[ 32111-21-0 ]
[ 1319197-08-4 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of 2-iodopyrazine (0.48 mL, 4.85 mmol) in dry THF (3 mL) was brought to 0 °C followed by the slowly addition of butylmagnesium chloride, 2.0M solution in THF (2.4 mL, 4.85 mmol). The resulting dark solution was stirred at 0°C for 30 min then a solution of <strong>[109179-31-9]2-bromo-3-methylbenzaldehyde</strong> (1.06 g, 5.34 mmol) in THF (2 mL) was slowly added and kept at 0 °C for 2 h. The mixture was quenched with saturated NH4C1 and extracted with DCM. The combined organics were washed with brine, dried over Na2S04, filtered, concentrated and purified by silica gel column chromatography using gradient 1 :1 hexanes/EtOAc to affrod a yellow-orange oil as (2-bromo-3- methylphenyl)(pyrazin-2-yl)methanol.

Reference： [1]Patent: WO2011/90911,2011,A1 .Location in patent: Page/Page column 70; 71

49
[ 1383711-38-3 ]
[ 32111-21-0 ]
[ 1383711-53-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In acetonitrile; at 90℃; for 13h;	General procedure: A mixture of tertiary propargylic alcohol 5 (0.13 mmol), (hetero)aryl halide (1.5 equiv), Pd(PPh3)4 (5 mol %), and K2CO3 (2.5 equiv) in CH3CN (1 mL) was heated at 90 C for 13 h. The reaction mixture was concentrated under reduced pressure to give the crude residue, which was diluted with ethyl acetate and washed with water. The organic layer was dried over MgSO4 and concentrated in vacuo to give a crude mixture, which was purified by silica gel column chromatography (hexane/ethyl acetate/dichloromethane) to afford the indolizinone 7.

Reference： [1]Tetrahedron,2012,vol. 68,p. 5464 - 5480

50
[ 5392-12-1 ]
[ 32111-21-0 ]
(R)-(2-methoxy-1-naphthyl)(pyrazin-2-yl)methanol [ No CAS ]
[ 1416473-71-6 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: In a Schlenk tube, flushed under argon, (R,R)-TADDOL (0.340 g, 0.728 mmol, 1.0 equiv) was dissolved in anhydrous toluene (C = 0.08 M). Next, n-BuLi (1.4 M in hexanes, 2.0 equiv) was slowly added at 10 C. After stirring at this temperature for 20 min, n-BuMgCl (2.0 M in THF, 1.0 equiv) was added at 10 C and the resulting solution was stirred for additional 20 min at the same temperature. n-BuLi (1.4 M in hexanes, 1.0 equiv) was added at 10 C and the mixture was stirred for 20 min at 10 C. 2-Iodopyrazine (0.150 g, 1.0 equiv) was then added at 30 C. The mixture was stirred for 1 h between 30 and 10 C. The reaction was monitored by TLC (eluent: ethyl acetate/cyclohexane 8/2). The medium was then cooled to 100 C and the aldehyde (1.82 mmol, 2.5 equiv) was added. The mixture was left at 100 C and stirred for 2 h. The reaction was quenched with a saturated aqueous solution of NH4Cl. The aqueous layer was extracted with ethyl acetate and acidified (pH = 3-4) using a sulphuric acid aqueous solution. The aqueous solution was then extracted with ethyl acetate. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The crude product was then purified by column chromatography over silica gel and analysed by chiral GC to determine enantiomeric ratios.

Reference： [1]Tetrahedron Asymmetry,2012,vol. 23,p. 1678 - 1682

51
[ 149947-15-9 ]
[ 32111-21-0 ]
[ 1428881-37-1 ]

Yield	Reaction Conditions	Operation in experiment
62.2%		Preparation 21 A: (3-Bromo-2-fluorophenyl)(pyrazin-2-yl)methanol [00173] To a stirring solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.195 mL, 1.970 mmol) in THF (3.28 mL) at 0 C was slowly added butyl magnesium chloride (0.985 mL, 1.970 mmol). The mixture was allowed to stir for 30 min, then 3-bromo-2-fluorobenzaldehyde (0.400 g, 1.970 mmol) was added. After 2 hr, the reaction was quenched with a saturated aqueous solution of NH4CI. The reaction mixture was diluted with (¾(¾. The layers were separated. The aqueous phase was extracted with CH2CI2 (2X). The organic phases were combined, dried over Na2S04, filtered, and concentrated to afford a yellow residue. The crude material was dissolved in a minimal amount of CH2CI2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (40 g column, 40 mL/min, 30-70% EtOAc in hexanes over 19 min, tr = 12 min) gave the title compound (347 mg, 1.226 mmol, 62.2% yield) as a yellow residue.

Reference： [1]Patent: WO2013/49263,2013,A1 .Location in patent: Paragraph 00172; 00173

52
[ 1450722-32-3 ]
[ 32111-21-0 ]
[ 1450722-39-0 ]

Yield	Reaction Conditions	Operation in experiment
48%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 20℃;Inert atmosphere;	General procedure: Compound 4 (1equiv per iodine atom), NEt3 (0.5mL), CuI (6mol%), and Pd(PPh3)2Cl2 (6mol%) were added to iododiazine (1mmol) in THF (5mL). The suspension was stirred at room temperature overnight under nitrogen atmosphere. The suspension was then diluted with a mixture of water and dichloromethane (1:1, 20mL) and the organic layer separated. The aqueous layer was extracted with dichloromethane (2×20mL). The combined organic extracts were dried over MgSO4, filtered, and evaporated.

Reference： [1]Tetrahedron,2013,vol. 69,p. 8392 - 8399

53
[ 780-69-8 ]
[ 32111-21-0 ]
[ 10199-00-5 ]
[ 29460-97-7 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 5378 - 5381

54
[ 17984-89-3 ]
[ 32111-21-0 ]
[ 56421-72-8 ]
[ 10199-00-5 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 5378 - 5381

55
[ 32111-21-0 ]
[ 213596-33-9 ]
[ 108030-81-5 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 1264 - 1267

56
[ 2314-97-8 ]
[ 32111-21-0 ]
[ 7440-66-6 ]
[ 61655-67-2 ]

Yield	Reaction Conditions	Operation in experiment
84 %Spectr.	Stage #1: iodotrifluoromethane; zinc With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone at 20℃; for 2h; Inert atmosphere; Stage #2: 2-iodopyrazine With copper(l) iodide at 50℃; for 24h; Inert atmosphere; chemoselective reaction;	Typical procedure for copper-catalyzed trifluoromethylation of aryl iodide. General procedure: To the suspension of zinc powder (without activation, 65.4 mg, 1.0 mmol, Aldrich 99.995% purity) in DMPU (0.5 mL), trifluoromethyl iodide (ca. 2.5 mmol, sufficiently dissolved in the solution) was added at room temperature under argon atmosphere. After the solution was stirred for 2 h at room temperature, CuI (1.9 mg, 0.01 mmol, 2 mol %), 1.10-phenanthroline (1.8 mg, 0.01 mmol, 2 mol %), and then aryl iodide 1a (138.0 mg, 0.5 mmol) were added. The reaction mixture was stirred at 50 °C for 24 h. After cooling to room temperature, the yield of product 2a was determined by 19F NMR analysis by using benzotrifluoride (BTF) as an internal standard. Except for 2c, all trifluoromethylated products 2 exhibited the same 1H, 13C, and 19F NMR spectra as reported before [14, 17, 29, 31-36].

Reference： [1]Nakamura, Yuzo; Fujiu, Motohiro; Murase, Tatsuya; Itoh, Yoshimitsu; Serizawa, Hiroki; Aikawa, Kohsuke; Mikami, Koichi [Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 2404 - 2409]

57
[ 32111-21-0 ]
[ 536-74-3 ]
[ 96129-41-8 ]

Yield	Reaction Conditions	Operation in experiment
61%	With C19H25CuN5(1+)*F6P(1-); potassium carbonate; In N,N-dimethyl-formamide; at 135 - 140℃;Sealed tube;	General procedure: A 20mL scintillation vial was charged with a Teflon stir bar, copper complex (0.1mmol), 76 potassium carbonate (0.75mmol), aryl iodide (0.5mmol), 77 phenylacetylene (0.75mmol) in 5mL non-anhydrous DMF in air. The vial was sealed and placed in an oil bath with pre-adjusted temperature at 135-140C. After the allowed time, the reaction mixture was cooled down, diluted with 25-30mL ethyl acetate, and filtered through a pad of silica gel. The solvent was then removed under vacuum and the residue was purified by column chromatography using mixtures of hexane and ethyl acetate to obtain analytically pure product.

Reference： [1]Israel Journal of Chemistry,2014,vol. 54,p. 371 - 380
[2]Journal of Organometallic Chemistry,2018,vol. 860,p. 98 - 105

58
[ 18412-57-2 ]
[ 32111-21-0 ]
[ 108030-81-5 ]

Yield	Reaction Conditions	Operation in experiment
35%	With copper(l) iodide; cesium fluoride; In N,N-dimethyl-formamide; at 120℃; for 48h;Sealed tube;	General procedure: In a glovebox, aryl iodide (1.0 mmol), CsF (228 mg, 1.5 mmol), and CuI (19.0 mg, 0.1 mmol) were weighed into a 4-dram borosilicate scintillation vial and dissolved in DMF (5 mL). Aryltriethoxysilane (1.0 mmol) was then added to the mixture, and the vial was tightly capped with a poly-seal cone-lined urea cap (Wheaton). The mixture was taken out of the glovebox and placed in an oil bath preheated to 120 C with vigorous stirring. After 48 h, the mixture was cooled to r.t., diluted with EtOAc (15 mL), and washed with H2O (2× 5 mL). The aqueous fraction was back-extracted with EtOAc (3 ×5 mL). The combined organic fractions were dried (Na2SO4) and cotton-filtered, and the solvent was removed on a rotary evaporator. The product was purified by column chromatography (silica gel, hexanes, hexanes-Et2O, or hexanes-EtOAc).

Reference： [1]Synthesis,2014,vol. 46,p. 1933 - 1937

59
[ 81290-20-2 ]
[ 32111-21-0 ]
[ 61655-67-2 ]

Yield	Reaction Conditions	Operation in experiment
98 %Chromat.	With potassium fluoride; copper (I) iodide; 1,10-Phenanthroline; Trimethyl borate In dimethyl sulfoxide at 60℃; for 5h; Inert atmosphere;
	With potassium fluoride; copper (I) iodide; 1,10-Phenanthroline; Trimethyl borate In dimethyl sulfoxide at 60℃; for 2h; Inert atmosphere;	Synthesis of 2-(trifluoromethyl)pyrazine Into a 1-L 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 2-iodopyrazine (20.00 g, 97.094 mmol, 1.00 equiv), DMSO (200.00 mL), CuI (3.70 g, 19.428 mmol, 0.20 equiv), 1,10-phenanthroline (3.50 g, 19.419 mmol, 0.2 equiv), KF (16.92 g, 291.239 mmol, 3.00 equiv), B(OMe)3 (30.27 g, 291.282 mmol, 3.00 equiv), TMSCF3 (41.42 g, 291.290 mmol, 3.00 equiv). The resulting solution was stirred for 2 hr at 60 degrees C in an oil bath. The resulting solution was diluted with 1 L of H2O. The resulting solution was extracted with 3x150 mL of ethyl acetate. The resulting mixture was washed with 1 x150 of H2O. The resulting mixture was washed with 1x100 mL of NaCl. The mixture was dried over anhydrous sodium sulfate and concentrated. The residue was applied onto a silica gel column and purified with ethyl acetate/petroleum ether (1:1). This resulted in crude of 2- (trifluoromethyl)pyrazine in 40 ml EA. Product is volatile. LC-MS: (ES, m/z): 149 [M+H]+
	With potassium fluoride; copper (I) iodide; 1,10-Phenanthroline; Trimethyl borate In dimethyl sulfoxide at 60℃; for 2h; Inert atmosphere;	Synthesis of 2-(trifluoromethyl)pyrazine Into a 1-L 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 2-iodopyrazine (20.00 g, 97.094 mmol, 1.00 equiv), DMSO (200.00 mL), CuI (3.70 g, 19.428 mmol, 0.20 equiv), 1,10-phenanthroline (3.50 g, 19.419 mmol, 0.2 equiv), KF (16.92 g, 291.239 mmol, 3.00 equiv), B(OMe)3 (30.27 g, 291.282 mmol, 3.00 equiv), TMSCF3 (41.42 g, 291.290 mmol, 3.00 equiv). The resulting solution was stirred for 2 hr at 60 degrees C in an oil bath. The resulting solution was diluted with 1 L of H2O. The resulting solution was extracted with 3x150 mL of ethyl acetate. The resulting mixture was washed with 1 x150 of H2O. The resulting mixture was washed with 1x100 mL of NaCl. The mixture was dried over anhydrous sodium sulfate and concentrated. The residue was applied onto a silica gel column and purified with ethyl acetate/petroleum ether (1:1). This resulted in crude of 2- (trifluoromethyl)pyrazine in 40 ml EA. Product is volatile. LC-MS: (ES, m/z): 149 [M+H]+

Reference： [1]Gonda, Zsombor; Kovacs, Szabolcs; Weber, Csaba; Gati, Tamas; Meszaros, Attila; Kotschy, Andras; Novak, Zoltan [Organic Letters, 2014, vol. 16, # 16, p. 4268 - 4271]
[2]Current Patent Assignee: NEWAVE PHARMACEUTICAL INC; GUANGZHOU LUPENG PHARMACEUTICAL LTD - WO2022/36171, 2022, A1 Location in patent: Page/Page column 21-22; 41
[3]Current Patent Assignee: NEWAVE PHARMACEUTICAL INC; GUANGZHOU LUPENG PHARMACEUTICAL LTD - WO2022/36171, 2022, A1 Location in patent: Page/Page column 21-22; 41

60
[ 163133-86-6 ]
[ 32111-21-0 ]
[ 1125867-36-8 ]

Yield	Reaction Conditions	Operation in experiment
66%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere;	A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1) (1.2g, 5.83mmol), pyrimidin-4-amine (2) (609mg, 6.4lmmol), Cs2003 (3.80g, 11.6Smmol) and Xantphos (148mg, 0.26mmol) in 1,4- Dioxane (l5mL) was purged with N2(g) for 10 mi Pd2(dba)3 (107mg, 0.12 mmol) was added and mixture was heated to 9000 for 3h. Reaction was cooled to rt and partitioned between water (300mL) and EtOAc (3 x lOOmL). Combined organics were washed with water (5OmL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography withCH2CI2/MeOH (1:0-9:1) to yield (3) (678mg, 66%).1H NMR (500 MHz, Methanol-d4), OH ppm: 9.06 (d, J=1.3 Hz, 1H), 8.74 (5, 1H), 8.42(d, J=6.0 Hz, 1H), 8.34 (dd, J=2.6, 1.5 Hz, 1H), 8.19 (d, J=2.7 Hz, 1H), 7.72 (dd,J=6.0, 1.0 Hz, 1H).LCMS (ES): Found 174.0 [M+H].
66%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere;	A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 ) (1 .2g, 5.83mmol), pyhmidin-4-amine (2) (609mg, 6.41 mmol), Cs2C03 (3.80g, 1 1 .65mmol) and Xantphos (148mg, 0.26mmol) in 1 ,4-Dioxane (15ml_) was purged with N2(g) for 10 min. Pd2(dba)3 (107mg, 0.12 mmol) was added and mixture was heated to 90C for 3h. Reaction was cooled to rt and partitioned between water (300ml_) and EtOAc (3 x 100ml_). Combined organics were washed with water (50m L), dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/MeOH (1:0-9:1) to yield (3) (678mg, 66%). 1H NMR (500 MHz, Methanol-d4), deltaEta ppm: 9.06 (d, J=1.3 Hz, 1H), 8.74 (s, 1H), 8.42 (d, J=6.0 Hz, 1H), 8.34 (dd, J=2.6, 1.5 Hz, 1H), 8.19 (d, J=2.7 Hz, 1H), 7.72 (dd, J=6.0, 1.0 Hz, 1H). LCMS (ES): Found 174.0 [M+H]+.
66%		Example DD (0434) -Hydroxy-4-[(pyrazin-2-yl)(pyrimidin-4-yl)amino]methyl}benzamide (0435) (0436) (0437) DD A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 ) (1.2g, 5.83mmol), pyrimidin-4-amine (2) (609mg, 6.41 mmol), Cs2C03 (3.80g, 11.65mmol) and Xantphos (148mg, 0.26mmol) in 1 ,4- dioxane (15mL) was purged with N2(g) for 10min. Pd2(dba)3 (107mg, 0.12 mmol) was added and mixture was heated to 90C for 3h. Reaction was cooled to rt and partitioned between water (300ml_) and EtOAc (3 x 100ml_). Combined organics were washed with water (50ml_), dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/MeOH (1 :0-9:1) to yield (3) (678mg, 66%). (0438) 1H NMR (500 MHz, Methanol-d4), deltaEta ppm: 9.06 (d, J=1.3 Hz, 1 H), 8.74 (s, 1 H), 8.42 (d, J=6.0 Hz, 1 H), 8.34 (dd, J=2.6, 1.5 Hz, 1 H), 8.19 (d, J=2.7 Hz, 1 H), 7.72 (dd, J=6.0, 1.0 Hz, 1 H). (0439) LCMS (ES): Found 174.0 [M+H]+.

Reference： [1]Patent: WO2014/181137,2014,A1 .Location in patent: Page/Page column 59; 60; 63
[2]Patent: WO2017/29514,2017,A1 .Location in patent: Page/Page column 90; 91
[3]Patent: WO2017/208032,2017,A1 .Location in patent: Page/Page column 67-68

61
[ 5469-70-5 ]
[ 32111-21-0 ]
C₈H₇N₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere;	A solution of 2-iodopyrazine (1) (2.40g, 11.65mmol), <strong>[5469-70-5]pyridazin-3-amine</strong> (2) (1.2g,12.82mmol), Cs2003 (7.6g, 23.3mmol) and Xantphos (297mg, 0.51 mmol) in dioxane(45mL) was purged with N2(g) for 10mm. Pd2(dba)3 (214mg, 0.23mmol) in dioxane(5mL) was added and mixture was heated to 90C for 3h. The reaction was cooledto rt and partitioned between water (200mL) and EtOAc (200mL). The insoluble solidwas filtered and put a-side. The phases were separated and aqueous was extractedwith EtOAc (200mL), then CH2CI2-IPA (200mL, 4:1). Combined organics were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/EtOAc (1:0-0:1) then EtOAc/MeOH (1:0-4:1) to yield (3). The solid [from filtration] was washed with water (lOOmL) and trituratedwith hot MeOH (3xlOOmL) and filtered. The filtrates were concentrated to yield a second batch of (3). The solid was further washed with water (lOOmL) and was sucked dry to yield a third batch of (3). All three batches were combined to give (3)(1.63g, 80%).1H NMR (500 MHz, DMSO-d6), OH ppm: 10.49 (5, 1H), 9.00 (d, J=1.2 Hz, 1H), 8.83(dd, J=4.6, 1.2 Hz, 1H), 8.27 (dd, J=2.5, 1.5 Hz, 1H), 8.16 (d, J=2.7 Hz, 1H), 8.06 (dd, J=9.1, 1.2 Hz, 1H), 7.60 (dd, J=9.1, 4.6 Hz, 1H).LCMS (ES): Found 174.2 [M+H].
80%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere;	A solution of 2-iodopyrazine (1 ) (2.40g, 1 1 .65mmol), <strong>[5469-70-5]pyridazin-3-amine</strong> (2) (1 .2g, 12.82mmol), Cs2C03 (7.6g, 23.3mmol) and Xantphos (297mg, 0.51 mmol) in dioxane (45ml_) was purged with N2(g) for 10min. Pd2(dba)3 (214mg, 0.23mmol) in dioxane (5mL) was added and mixture was heated to 90C for 3h. The reaction was cooled to rt and partitioned between water (200m L) and EtOAc (200ml_). The insoluble solid was filtered and put a-side. The phases were separated and aqueous was extracted with EtOAc (200m L), then CH2CI2-IPA (200ml_, 4:1). Combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/EtOAc (1:0-0:1) then EtOAc/MeOH (1:0-4:1) to yield (3). The solid [from filtration] was washed with water (100ml_) and triturated with hot MeOH (3x100ml_) and filtered. The filtrates were concentrated to yield a second batch of (3). The solid was further washed with water (100ml_) and was sucked dry to yield a third batch of (3). All three batches were combined to give (3) (1.63g, 80%). 1H NMR (500 MHz, DMSO-d6), deltaEta ppm: 10.49 (s, 1H), 9.00 (d, J=1.2 Hz, 1H), 8.83 (dd, J=4.6, 1.2 Hz, 1H), 8.27 (dd, J=2.5, 1.5 Hz, 1H), 8.16 (d, J=2.7 Hz, 1H), 8.06 (dd, J=9.1, 1.2 Hz, 1H), 7.60 (dd, J=9.1, 4.6 Hz, 1H). LCMS (ES): Found 174.2 [M+H]+.
80%		Example MM (0524) N-Hydroxy-4-[(pyrazin-2-yl)(pyridazin-3-yl)amino]methyl}benzamide (0525) (0526) MM (0527) A solution of 2-iodopyrazine (1 ) (2.40g, 11.65mmol), <strong>[5469-70-5]pyridazin-3-amine</strong> (2) (1.2g, 12.82mmol), Cs2C03 (7.6g, 23.3mmol) and Xantphos (297mg, 0.51 mmol) in dioxane (45mL) was purged with N2(g) for 10min. Pd2(dba)3 (214mg, 0.23mmol) in dioxane (5ml_) was added and the mixture was heated to 90C for 3h. The reaction was cooled to rt and partitioned between water (200ml_) and EtOAc (200ml_). The insoluble solid was filtered and put a-side. The phases were separated and the aqueous layer was extracted with EtOAc (200ml_), then CH2CI2-IPA (200ml_, 4:1). Combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/EtOAc (1 :0-0:1) then EtOAc/MeOH (1 :0-4:1) to yield (3). The solid [from filtration] was washed with water (100ml_) and triturated with hot MeOH (3x100ml_) and filtered. The filtrates were concentrated to yield a second batch of (3). The solid was further washed with water (100ml_) and was sucked dry to yield a third batch of (3). All three batches were combined to give (3) (1.63g, 80%). (0528) 1 H NMR (500 MHz, DMSO-cfe), deltaEta ppm: 10.49 (s, 1 H), 9.00 (d, J=1.2 Hz, 1 H), 8.83 (dd, J=4.6, 1.2 Hz, 1 H), 8.27 (dd, J=2.5, 1.5 Hz, 1 H), 8.16 (d, J=2.7 Hz, 1 H), 8.06 (dd, J=9.1 , 1.2 Hz, 1 H), 7.60 (dd, J=9.1 , 4.6 Hz, 1 H). (0529) LCMS (ES): Found 174.2 [M+H]+.

Reference： [1]Patent: WO2014/181137,2014,A1 .Location in patent: Page/Page column 70
[2]Patent: WO2017/29514,2017,A1 .Location in patent: Page/Page column 102; 103
[3]Patent: WO2017/208032,2017,A1 .Location in patent: Page/Page column 78-79

62
[ 10201-73-7 ]
[ 32111-21-0 ]
C₁₀H₁₀N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere;	A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1) (1.34g, 6.Slmmol), 4-methoxypyridin-2-amine (2)(0.85g, 6.83mmol), Cs2003 (4.24g, 13.01 mmol) and Xantphos (0.17g, 0.29mmol) indioxane (22mL) was purged with N2(g) for 10mm then Pd2(dba)3 (0.12g, 0.l3mmol) was added, re-purged for -5mm and reaction was heated to 90C for 4h. Once cooled down to rt, the mixture was partitioned between H20 (l5OmL) and EtOAc (3 x l2OmL). Combined organics were dried over Na2504, filtered and concentrated invacuo. The residue was purified by flash column chromatography withCH2CI2/EtOAc (9:1-0:1) to yield (3) (809mg, 61%) as a yellow solid.1H NMR (500 MHz, Chloroform-d), OH ppm: 8.70 (d, J=1.3 Hz, 1H), 8.11-8.22 (m,3H), 8.08 (d, J=2.7 Hz, 1H), 7.43 (d, J=2.2 Hz, 1H), 6.52 (dd, J=5.8, 2.3 Hz, 1H),3.88 (5, 3H).LCMS (ES): Found 203.2 [M+H].
61%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere;	A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 ) (1 .34g, 6.51 mmol), 4-methoxypyridin-2-amine (2) (0.85g, 6.83mmol), Cs2C03 (4.24g, 13.01 mmol) and Xantphos (0.17g, 0.29mmol) in dioxane (22mL) was purged with N2(g) for 10min then Pd2(dba)3 (0.12g, 0.13mmol) was added, re-purged for ~5min and reaction was heated to 90C for 4h. Once cooled down to rt, the mixture was partitioned between H20 (150ml_) and EtOAc (3 x 120ml_). Combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/EtOAc (9: 1 -0: 1 ) to yield (3) (809mg, 61 %) as a yellow solid. 1 H NMR (500 MHz, Chloroform-d), deltaEta ppm: 8.70 (d, J=1 .3 Hz, 1 H), 8.1 1 -8.22 (m, 3H), 8.08 (d, J=2.7 Hz, 1 H), 7.43 (d, J=2.2 Hz, 1 H), 6.52 (dd, J=5.8, 2.3 Hz, 1 H), 3.88 (s, 3H). LCMS (ES): Found 203.2 [M+H]+.
61%		Example PP (0552) (0553) PP (0554) A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 ) (1.34g, 6.51 mmol), 4-methoxypyridin-2-amine (2) (0.85g, 6.83mmol), Cs2C03 (4.24g, 13.01 mmol) and Xantphos (0.17g, 0.29mmol) in dioxane (22ml_) was purged with N2(g) for 10min then Pd2(dba)3 (0.12g, 0.13mmol) was added, re-purged for ~5min and reaction was heated to 90C for 4h. Once cooled down to rt, the mixture was partitioned between H20 (150ml_) and EtOAc (3 x 120ml_). Combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/EtOAc (9: 1-0:1) to yield (3) (809mg, 61 %) as a yellow solid. (0555) 1 H NMR (500 MHz, Chloroform-d), deltaEta ppm: 8.70 (d, J=1.3 Hz, 1 H), 8.1 1-8.22 (m, 3H), 8.08 (d, J=2.7 Hz, 1 H), 7.43 (d, J=2.2 Hz, 1 H), 6.52 (dd, J=5.8, 2.3 Hz, 1 H), 3.88 (s, 3H). (0556) LCMS (ES): Found 203.2 [M+H]+.

Reference： [1]Patent: WO2014/181137,2014,A1 .Location in patent: Page/Page column 74
[2]Patent: WO2017/29514,2017,A1 .Location in patent: Page/Page column 106; 107
[3]Patent: WO2017/208032,2017,A1 .Location in patent: Page/Page column 82

63
[ 6232-11-7 ]
[ 32111-21-0 ]
C₁₃H₁₃N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With copper(l) iodide; potassium carbonate; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	To a solution of methyl 4-(aminomethyl)benzoate hydrochloride (1 .47g, 7.3mmol) in DMSO (14ml_) was added <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 g, 4.9mmol) followed by K2C03 (1 .7g, 12.1 mmol) under Ar(g). After 2 min vigorous stirring, Cul (46mg, 0.2mmol) was added and the mixture was left to stir at rt overnight. It was partitioned between EtOAc (150ml_) and 50% brine (50ml_) and the organic layer separated, the aqueous extracted with EtOAc (2 x 15ml_), before the combined organic phase was washed with 50% brine (15ml_), dried (MgS04), and concentrated in vacuo. The residue was purified by flash column chromatography with Hexane/EtOAc (7:3-0: 1 ) to yield (3) (670mg, 57%) as a white solid. 1 H NMR (300MHz, CHLOROFORM-d) deltaEta ppm: 7.76-8.1 1 (m, 5H), 7.43 (d, J=8.5 Hz, 2H), 5.01 -5.16 (m, 1 H), 4.66 (d, J=5.8 Hz, 2H), 3.92 (s, 3H). LCMS (ES): Found 352.0 [M+H]+

Reference： [1]Patent: WO2014/181137,2014,A1 .Location in patent: Page/Page column 75; 76
[2]Patent: WO2017/29514,2017,A1 .Location in patent: Page/Page column 108

64
[ 5049-61-6 ]
[ 32111-21-0 ]
[ 533930-18-6 ]

Yield	Reaction Conditions	Operation in experiment
51%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere;	A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1) (1.2g, 5.83mmol), pyrazin-2-amine (2) (609mg,6.4mmol), Cs2003 (3.80g, 11.7mmol) and Xantphos (148mg, 0.26mmol) in dioxane(25mL) was purged with N2(g) for 10mm. Pd2(dba)3 (1 07mg, 0.l2mmol) was addedand mixture was heated to 90C for 3h. Reaction cooled to rt and poured onto water(200mL), extracted with EtOAc (2 x l5OmL) and CH2CI2-IPA (l5OmL, 4:1).Combined organics were dried over Na2504, filtered and concentrated in vacuo.Flash column chromatography with heptane/EtOAc (4:1-0:1) then EtOAc/MeOH(1:0-3:1) yielded (3) as an off white solid (210 mg, 51%).1H NMR (500 MHz, Chloroform-d), OH ppm: 8.99 (d, J=1.4 Hz, 2H), 8.30 (dd, J=2.6,1.5 Hz, 2H), 8.11 (d, J=2.7 Hz, 2H).LCMS (ES): Found 174.1 [M+H].
51%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 3h;Inert atmosphere;	A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 ) (1 .2g, 5.83mmol), pyrazin-2-amine (2) (609mg, 6.4mmol), Cs2C03 (3.80g, 1 1 .7mmol) and Xantphos (148mg, 0.26mmol) in dioxane (25mL) was purged with N2(g) for 10min. Pd2(dba)3 (107mg, 0.12mmol) was added and mixture was heated to 90C for 3h. Reaction cooled to rt and poured onto water (200m L), extracted with EtOAc (2 x 150mL) and CH2CI2-I PA (150mL, 4: 1 ). Combined organics were dried over Na2S04, filtered and concentrated in vacuo. Flash column chromatography with heptane/EtOAc (4: 1 - 0: 1 ) then EtOAc/MeOH (1 :0-3: 1 ) yielded (3) as an off white solid (210 mg, 51 %). 1 H NMR (500 MHz, Chloroform-d), deltaEta ppm: 8.99 (d, J=1 .4 Hz, 2H), 8.30 (dd, J=2.6, 1 .5 Hz, 2H), 8.1 1 (d, J=2.7 Hz, 2H). LCMS (ES): Found 174.1 [M+H]+.
51%		Example GG (0464) 4-[Bis(pyrazin-2-yl)amino]methyl}-N-hydroxybenzamide (0465) (0466) (0467) GG (0468) A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 ) (1.2g, 5.83mmol), pyrazin-2-amine (2) (609mg, (0469) 6.4mmol), Cs2C03 (3.80g, 11.7mmol) and Xantphos (148mg, 0.26mmol) in dioxane (0470) (25mL) was purged with N2(g) for 10min. Pd2(dba)3 (107mg, 0.12mmol) was added and mixture was heated to 90C for 3h. Reaction cooled to rt and poured onto water (0471) (200ml_), extracted with EtOAc (2 x 150ml_) and CH2CI2-IPA (150ml_, 4: 1). (0472) Combined organics were dried over Na2S04, filtered and concentrated in vacuo. (0473) Flash column chromatography with heptane/EtOAc (4: 1-0:1) then EtOAc/MeOH (0474) (1 :0-3:1) yielded (3) as an off white solid (210 mg, 51 %). (0475) 1 H NMR (500 MHz, Chloroform-d), deltaEta ppm: 8.99 (d, J=1.4 Hz, 2H), 8.30 (dd, J=2.6, (0476) 1.5 Hz, 2H), 8.11 (d, J=2.7 Hz, 2H). (0477) LCMS (ES): Found 174.1 [M+H]+.

Reference： [1]Patent: WO2014/181137,2014,A1 .Location in patent: Page/Page column 63
[2]Patent: WO2017/29514,2017,A1 .Location in patent: Page/Page column 94
[3]Patent: WO2017/208032,2017,A1 .Location in patent: Page/Page column 71

65
[ 95-16-9 ]
[ 32111-21-0 ]
[ 129242-49-5 ]

Yield	Reaction Conditions	Operation in experiment
42%	With iron(III) chloride; trans-1,2-Diaminocyclohexane; sodium hydroxide; In water; at 110℃; for 24h;Green chemistry;	General procedure: FeCl3 (32 mg, 20 mol%), trans-1,2-diaminocyclohexane (48 L, 40 mol%), benzothiazole (108 mul, 1.0 mmol), (hetero)aryl iodides(1.5 mmol), NaOH (0.12 g, 3.0 mmol) and H2O (1.0 mL) were loaded into a reaction tubeequipped with a septum in the presence of Teflon coated magnetic stirrer bar under air. The tubewas then placed into a preheated oil bath (110 C) and stirred for 24 hours. After completion ofreaction as judged by GC analysis, the reaction tube was allowed to cool to room temperatureand quenched with water. EtOAc was then added for dilution. The organic layer was separatedand the aqueous layer was washed with EtOAc. The filtrate was concentrated under reducedpressure. The crude products were purified by flash column chromatography on silica gel (230-400 mesh) to afford the desired product.
42%	With iron(III) chloride; (S,S)-1,2-diaminocyclohexane; sodium hydroxide; In water; at 110℃; for 24h;	General procedure: FeCl3 (32 mg, 20 mol%), trans-1,2-diaminocyclohexane(48 muL, 40 mol%), benzothiazole (108 muL, 1.0 mmol),(hetero)aryl iodide (1.5 mmol), NaOH (0.12 g, 3.0 mmol),and H2O (1.0 mL) were loaded into a reaction tube equippedwith a septum in the presence of Teflon-coated magneticstirrer bar on bench-top under air. The tube was then placedinto a preheated oil bath (110 C) and stirred for 24 h. Aftercompletion of reaction as judged by GC analysis, thereaction tube was allowed to cool to r.t. EtOAc was addedfor product extraction. The organic layer was separated, andthe aqueous layer was further washed with EtOAc (3× ca. 10mL). The organic part was concentrated under reducedpressure. The crude products were purified by flash columnchromatography on silica gel (230-400 mesh) to afford thedesired product (see Supporting Information for details).

Reference： [1]Synlett,2014,vol. 25,p. 2743 - 2747
[2]Synlett,2014,vol. 25,p. 2743 - 2747

66
Zn(CF3)2(1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone)2 [ No CAS ]
[ 32111-21-0 ]
[ 61655-67-2 ]

Yield	Reaction Conditions	Operation in experiment
92 %Spectr.	With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; copper(l) iodide at 50℃; for 24h; Inert atmosphere;

Reference： [1]Aikawa, Kohsuke; Nakamura, Yuzo; Yokota, Yuki; Toya, Wataru; Mikami, Koichi [Chemistry - A European Journal, 2015, vol. 21, # 1, p. 96 - 100]

67
[ 32111-21-0 ]
[ 10199-00-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	With palladium diacetate; potassium carbonate; In N,N-dimethyl-formamide; isopropyl alcohol; at 100℃; for 2h;	General procedure: A 100 mL round bottom flask was equipped with a magnetic stir bar and charged with the appropriate aryl iodide (1 equiv), K2CO3 (1.5 equiv), iPrOH (2 equiv), Pd(OAc)2 (5 mol %), and a sufficient volume of DMF to make a 0.35 M solution. The reaction mixture was placed under nitrogen and heated to 100 C for 2-5 h until the starting material was consumed as judged by TLC analysis. The reaction mixture was cooled to room temperature and brine (40 mL) was added. The resulting mixture was transferred to a separatory funnel and extracted with EtOAc (3 × 75 mL). The organic layers were combined, washed with brine (1 × 75 mL), dried with Na2SO4, and the solvent was removed in vacuo to afford the crude product as a solid. The crude solid was purified by flash column chromatography or by recrystallization.
70%	With palladium diacetate; potassium carbonate; at 120℃; for 48h;Inert atmosphere;	2-Iodopyrazine (5.00 g, 24.3 mmol), PdII(OAc)2 (34 mg, 0.151 mmol), K2CO3 (3.4 g, 24.6 mmol) and poly(ethylene glycol) (Mw 4000, 24.0 g) were combined in an argon-purged flask. The mixture was gradually heated to 120 C and the temperature maintained for 48 h with stirring. The mixture was cooled to ca. 80 C and warm water (30 mL) was added to prevent solidification. On cooling to room temperature, further water (100 mL) was added and the suspension exhaustively extracted with ethyl acetate. The combined extracts were washed once with saturated aqueous Na2S2O3 and then thrice with brine. The organic layer was dried over MgSO4 and solvent removed under vacuum. The residue was triturated with n-pentane and the white crystalline solid filtered off, washed with n-pentane and dried. Yield: 1.35 g (70%). deltaH (400 MHz, CDCl3) 9.60 (2H, d, J=1.1Hz), 8.68-8.66 (4H). GC-MS: m/z=158 ([M]+). Anal. Calc. for C8H6N4: C, 60.8; H, 3.8; N, 35.4. Found: C, 60.4; H, 3.4; N, 35.8%.

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 61 - 65
[2]Organic Syntheses,2016,vol. 93,p. 178 - 199
[3]Polyhedron,2015,vol. 96,p. 57 - 65
[4]Organic Letters,2020,vol. 22,p. 3045 - 3049

68
trimethylsilyl 2-chloro-2,2-difluoroacetate [ No CAS ]
[ 32111-21-0 ]
[ 61655-67-2 ]

Yield	Reaction Conditions	Operation in experiment
57 %Spectr.	With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; silver fluoride In N,N-dimethyl-formamide at 100℃; for 2h; Inert atmosphere; Sealed tube;
92 %Spectr.	With potassium fluoride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 90℃; for 4h; Sealed tube; Inert atmosphere;

Reference： [1]Zhang, Xiaomin; Wang, Jian; Wan, Zehong [Organic Letters, 2015, vol. 17, # 9, p. 2086 - 2089]
[2]Wang, Jian; Zhang, Xiaomin; Wan, Zehong; Ren, Feng [Organic Process Research and Development, 2016, vol. 20, # 4, p. 836 - 839]

69
[(2,2'-bipyridine)₂Cu][O₂CCF₂Cl] [ No CAS ]
[ 32111-21-0 ]
[ 61655-67-2 ]

Yield	Reaction Conditions	Operation in experiment
73 %Spectr.	With cesium fluoride; sodium hydroxide In N,N-dimethyl-formamide at 75℃; for 3h; Inert atmosphere; Sealed tube;

Reference： [1]Lin, Xiaoxi; Li, Zhengyu; Han, Xiaoyan; Weng, Zhiqiang [RSC Advances, 2016, vol. 6, # 79, p. 75465 - 75469]

70
[ 271-44-3 ]
[ 32111-21-0 ]
1-(pyrazin-2-yl)-1H-indazole [ No CAS ]
C₁₁H₈N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; caesium carbonate; In aq. buffer; at 60℃; for 2h;	General procedure: To a mixture of indazoles, indoles, or indolin-2-ones (1 equiv), aryl halides (1.2 equiv), cesium carbonate (2.5 equiv), copper (I) iodide (0.2 equiv) in Tween 20/water (2%, w/w, 0.2M) was added trans-N1,N2-dimethylcyclohexane-1,2-diamine (0.8 equiv). The reaction mixture was stirred at 60C for 2h. The reaction mixture was extracted with ethyl acetate (20mL×3). The organic layers were combined, washed with brine (50mL), dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash chromatography on silica gel and eluted with PE/EA to afford the desired product 3, 5, 8 and 10.

Reference： [1]Tetrahedron,2017,vol. 73,p. 172 - 178

71
[ 6609-56-9 ]
[ 32111-21-0 ]
2-[2-(2-methoxyphenyl) ethynyl]pyrazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine; copper(l) iodide; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; at 20℃; for 72h;	2-[2-(2-Methoxyphenyl)ethynyl]pyrazine 2-Iodopyrazine (4.7 g, 22.85 mmol) and ethnylanisole (3.02 g, 22.85 mmol) were combined in THF (470 mL) and piperidine (4.06 mL, 41.1 mmol). The solution was then vacuum degassed three times releasing to Na. CuI (87 mg, 0.46 mmol) and PdCl2(dppf).DCM (373 mg, 0.46 mmol) were added and the resulting mixture stirred at ambient temperature for 72 hours. The reaction mixture was then concentrated in vacuo and the residue partitioned between EtOAc (50 mL) and 10% aqueous citric acid (25 mL). The phases were separated and the aqueous extracted further with EtOAc (50 mL). The combined organics were concentrated to give 6.4 g of a black oil. This was purified by chromatography [1:4 EtOAc:Heptane] to give 4.04 g of 2-(2-(2-methoxyphenyl)ethynyl)pyrazine (84% yield, 93% purity by LCMS); 1H NMR (270 MHz, CDCl3) δ 3.92 (s, 3H), 6.94 (m, 2H), 7.37 (m, 1H), 7.56 (dd, 1H, J=7.3 Hz, 1.6 Hz), 8.46 (d, 1H, J=2.7 Hz), 8.57 (t, 1H, J=2.2 Hz), 8.77 (d, 1H, J=1.6 Hz).

Reference： [1]Patent: US2016/326122,2016,A1 .Location in patent: Paragraph 0196; 0199; 0200

72
Phe-Wang resin [ No CAS ]
[ 18414-58-9 ]
[ 32111-21-0 ]
[ 114457-94-2 ]

Reference： [1]Organic Letters,2017,vol. 19,p. 2873 - 2876

73
methyl 4-(aminomethyl)benzoate hydrochloride [ No CAS ]
[ 32111-21-0 ]
C₁₃H₁₃N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With copper(l) iodide; potassium carbonate; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	Example QQ (0561) N-Hydroxy-4-[(pyrazin-2-yl)[6-(trifluoromethyl)pyrazin-2- (0562) (0563) QQ (0564) To a solution of methyl 4-(aminomethyl)benzoate hydrochloride (1.47g, 7.3mmol) in DMSO (14mL) was added <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 g, 4.9mmol) followed by K2C03 (1.7g, 12.1 mmol) under Ar(g). After 2min vigorous stirring, Cul (46mg, 0.2mmol) was added and the mixture was left to stir at rt overnight. It was partitioned between EtOAc (150ml_) and 50% brine (50ml_) and the organic layer separated, the aqueous layer was extracted with EtOAc (2 x 15ml_), before the combined organic phase was washed with 50% brine (15ml_), dried (MgS04) and concentrated in vacuo. The residue was purified by flash column chromatography with Hexane/EtOAc (7:3-0:1) to yield (3) (670mg, 57%) as a white solid. (0565) 1 H NMR (300MHz, CHLOROFORM-d) deltaEta ppm: 7.76-8.1 1 (m, 5H), 7.43 (d, J=8.5 Hz, 2H), 5.01-5.16 (m, 1 H), 4.66 (d, J=5.8 Hz, 2H), 3.92 (s, 3H). (0566) LCMS (ES): Found 352.0 [M+H]+.

Reference： [1]Patent: WO2017/208032,2017,A1 .Location in patent: Page/Page column 84

74
[ 1496523-98-8 ]
[ 32111-21-0 ]
diethyl [(pyrazin-2-yl)difluoromethyl]phosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With bis-triphenylphosphine-palladium(II) chloride; In acetonitrile; at 40℃; for 16h;	General procedure: A tube was loaded with CuCl (50 mg, 0.50 mmol) and CsF (228 mg,1.50 mmol) and sealed with a rubber septum. Anhydrous acetonitrile (1 mL) was added and the mixture was cooled to 0 C. Diethyl [(trimethylsilyl)difluoromethyl]phosphonate (neat, 325 mg, 1.25 mmol) was added and the mixture was heated at 40C for 1 h, cooled to 0 C and stirred at this temperature for 1 h. Pd(PPh3)Cl2 (18 mg,0.025 mmol) was added followed by a solution of the corresponding iodoarene 1 (0.50 mmol) in MeCN (1 mL). The suspension was stirred for 16 h at 40C. The reaction mixture was diluted with diethyl ether(15 mL), the organic layer was washed with water (15 mL), Na2CO3 (concentrated solution, 15 mL), dried over Na2SO4, and solvents were carefully removed under vacuum. Reverse-phase chromatography (H2O/MeCN or MeOH, gradient: 9:1 to 0:1, rate: 1% MeCN or MeOH per minute) gave the product 2.

Reference： [1]Synthesis,2018,vol. 50,p. 778 - 784

75
[ 624-92-0 ]
[ 32111-21-0 ]
[ 21948-70-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2018,vol. 16,p. 1543 - 1551

76
(2-(methylthio)benzo[d]thiazol-6-yl)methanamine [ No CAS ]
[ 32111-21-0 ]
N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With cesium acetate; copper; In dimethyl sulfoxide; at 90℃; for 1h;	To a suspension of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (110 mg, 0.53 mmol) and (2-(methylthio)benzo[djthiazol-6-yl)methanamine(75 mg, 0.36 mmol) in DMSO (713 tl) were added copper (2.3 mg, 0.036 mmol) and cesium acetate (137 mg, 0.7 13 mmol) and the resulting mixture was stirred at 90 C for 1 h. The reaction mixture was purified by mass-triggered preparative HPLC (Mobile phase: A = 0.1% TFA/H20, B = 0.1% TFAIMeCN; Gradient: B = 10 - 90%; 12 mm; Column: C18) to give thetitle compound (61 mg, 68%) as a brown amorphous material. MS (ES+) C,3H,2N452requires: 288, found: 289 [M+Hf?. ?H NMR (600 MHz, Acetone-d6) oe 8.67 (br s, 1H), 8.33 -8.00 (m, 3H), 7.97 (s, 1H), 7.79 (d, J= 8.3 Hz, 1H), 7.51 (d, J= 8.5 Hz, OH), 4.78 (s, 2H),2.80 (s, 3H)

Reference： [1]Patent: WO2018/81276,2018,A1 .Location in patent: Page/Page column 121

77
[ 32111-21-0 ]
[ 205865-67-4 ]
2,2-difluoro-2-(pyrazin-2-yl)acetic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With potassium fluoride; copper(l) iodide; In dimethyl sulfoxide; at 60℃; for 15h;Inert atmosphere; Schlenk technique;	2,2-Difluoro-2- (pyrazin-2-yl) acetic acid ethyl ester (Compound 3d) was prepared according to the following procedure.Iodopyrazine (103.0 mg, 0.5 mmol), copper (I) iodide (190.5 mg, 1.0 mmol), potassium fluoride (58.1 mg, 1.0 mmol) and DMSO (2.0 mL) are placed in a Schlenk tube. Finally, alpha- (trimethylsilyl) difluoroacetic acid ethyl ester (Compound 2a) (196.3 mg, 1.0 mmol) was added and the mixture was stirred at 60 C. for 15 hours under a nitrogen atmosphere. After the reaction, trifluoroethanol (50.0 mg, 0.5 mmol) was added as an internal standard and measurement by 19 F-NMR revealed that 2,2-difluoro-2- (pyrazin-2-yl) acetic acid ethyl ester 3d) was produced in a yield of 70%. The reaction mixture was extracted with ethyl acetate, washed with water and dried over anhydrous sodium sulfate. Anhydrous sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hexane: EtOAc = 20: 1, 10: 1, 5: 1)) to give 2,2-difluoro-2- (pyrazin-2- yl) acetic acid ethyl ester 3d) (58.4 mg, 0.29 mmol, yield: 58%).

Reference： [1]Patent: JP5679855,2015,B2 .Location in patent: Paragraph 0106-0108

78
[ 32111-21-0 ]
N-t-butoxycarbonyl-3-iodo-D-alanine methyl ester [ No CAS ]
methyl (2R)-2-[(tert-butoxy)carbonyl]amino}-3-(pyrazin-2-yl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); iodine; zinc; In N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere;	Zinc powder (0.24 g, 3.6 mmol) was added to a dry flask purged with nitrogen. Dry DMF (2 ml) was added followed by iodine (86 mg, 0.4 mmol). The solution changed from colourless to yellow and then back to colourless. Methyl (2S)-2-[(tert-butoxy)carbonyl]amino}-3- lodopropanoate (0.40 g, 1.2 mmol) was added, followed by iodine (86 mg, 0.4 mmol). The solution was stirred at ambient temperature, with an exotherm observed. To this solution was added Pd2(dba)3(28 mg, 0.04 mmol), SPhos (24 mg, 0.12 mmol) and <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.32 g, 1.5 mmol). The RM was stirred at rt under nitrogen for 18 h. The RM was filtered twice and then purified by FCC (silica, EtOAc / hexane) to give the desired product.Y = 90 % MS ES+: 282

Reference： [1]Patent: WO2018/167468,2018,A1 .Location in patent: Page/Page column 83

79
[ 547-63-7 ]
[ 32111-21-0 ]
[ 950604-80-5 ]

Yield	Reaction Conditions	Operation in experiment
72%		General procedure: Inside the glovebox, lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 70.7 mg, 0.48 mmol, 1.2 eq.) was dissolved in toluene (1.5 mL) and carbonyl compound (3, 0.48 mmol, 1.2 eq.) was added. After 15 min of stirring at ambient temperature a solution of Pd(I) iodo dimer (2, 3.5 mg, 0.004 mmol, 1 mol% for aryl iodides; 17.4 mg, 0.02 mmol, 5 mol% for aryl bromides) and aryl halide (4, X = I or Br, 0.4 mmol, 1.0 eq.) in toluene (0.5 mL) was added. After 4-18 h of further stirring at ambient temperature (reaction progress was monitored by GCMS), the crude was directly adsorbed onto silica (washing with diethyl ether) and purified by flash column chromatography.

Reference： [1]Synthesis,2018,vol. 50,p. 4471 - 4475

80
[ 32111-21-0 ]
[ 272-52-6 ]
3-(pyrazin-2-yl)-1H-pyrazolo[4,3-b]pyridine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2018,vol. 83,p. 12847 - 12854

81
[ 32111-21-0 ]
[ 5049-61-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With copper(I) oxide; ammonia; potassium carbonate; In 1,4-dioxane; at 140℃; under 7757.43 Torr; for 16h;	To a stirred solution of 0.1 equiv. of Cu2O in dioxane (20 mL) was added 3.0 equiv.of K2CO3. To the resulting suspension added 1.0 equiv. of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> and ammonia gas was purged 150 psi. The resulting reaction mixture was allowed to reflux for 16 h at 140 C. After completion of the reaction, the reaction mixture cooled to room temperature and filter using celite-pad. Filtrate was extracted with 30 % ethyl acetate-hexane (10 mL × 3). The organic layer was washed with brine and dried over sodium sulphate and concentrated in vacuum to get pure pale brown pyrazin-2-amine (2), yield: 92 %; m.p. 112-113 C. IR (KBr, numax, cm-1): 3355, 3290, 3057, 2936, 1638, 1501, 1455, 1373,1291; 1H NMR (400 MHz, DMSO-d6): delta 6.36 (brs, 2H, NH2),7.64 (s, 1H, C5-H of pyrazine), 7.84 (s, 2H, C3-H and C6-H ofpyrazine); LC-MS: m/z 96.25 [M+H]+. Anal. calcd. (%) for C4H5N3: C 50.52, H 5.30, N 44.18. Found (%): C 50.64, H5.31, N 44.20.

Reference： [1]Asian Journal of Chemistry,2020,vol. 32,p. 84 - 90
[2]Organic and Biomolecular Chemistry,2019,vol. 17,p. 1791 - 1795

82
[ 7150-72-3 ]
[ 32111-21-0 ]
tert-butyl (2-(pyrazin-2-yl)ethyl)carbamate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 4147 - 4153

83
[ 32111-21-0 ]
[ 183673-70-3 ]
C₁₆H₂₁N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65.9%	With copper(I) oxide; In N,N-dimethyl acetamide; at 140℃; for 24h;	To a solution of compound 1 (1 g, 3.71 mmol, 1 eq) in DMA (3 mL) was added compound 1A (382.45 mg, 1.86 mmol, 182.99 uL, 0.5 eq) and Cu2O (132.84 mg, 928.35 umol, 94.88 uL, 0.25 eq). The mixture was stirred at 140C for 24 h. LCMS and show the reaction was completed. The mixture was filtered and the filter liquor was concentrated in vacuum. The crude product was purified by prep-HPLC (column: Agela innoval ods-2 250*80mm; mobile phase: [water (0.1%TFA)-ACN]; B%: 16%-46%, 30 min) to give compound 2 (0.85 g, 2.45 mmol, 65.90% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 8.78 (s, 1 H) 8.65 (s, 2 H) 6.95 (s, 1 H) 4.01 (d, J = 13.2 Hz, 2 H) 3.26 - 3.39 (m, 2 H) 2.16 (ddd, J = 13.6, 9.5, 4.0 Hz, 2 H) 1.82 (d, J = 13.4 Hz, 2 H) 1.49 (s, 9 H). LCMS: RT = 1.048 min, MS cal.:347.4, [M-56+H] + = 292.0.

Reference： [1]Patent: WO2019/136442,2019,A1 .Location in patent: Paragraph 00519

84
[ 290-37-9 ]
[ 32111-21-0 ]
[ 10199-00-5 ]

Reference： [1]Chemical Communications,2018,vol. 54,p. 13220 - 13223

85
[ 17376-04-4 ]
[ 32111-21-0 ]
[ 91391-83-2 ]

Yield	Reaction Conditions	Operation in experiment
96%		General procedure: The insertion step 1: Alkyl iodide (1 mmol), indium (172.2 mg, 1.5 mmol), copper sulfate pentahydrate (25.0 mg, 0.1 mmol), and analytical grade THF (1.5 mL) and H2O (0.5 mL) were added in a flask equipped with a septum and a magnetic stir bar. The reaction mixture was vigorously stirred at 60 oC for 12 hrs. Then the upper clear solution was carefully separated from the bottom black precipitate by centrifugal. The remaining black precipitate was additionally stirred with THF(3 mL), and the THF layer was carefully separated from bottom precipitate by pipette. The combined organic layers were concentrated under vacuum. The crude mixture was directly used in the next step without further purification. The cross-coupling step 2: To the above residue was added aryl halide (0.7 mmol), LiCl (84.8 mg,2 mmol), Pd(PPh3)4 (57.8 mg, 0.05 mmol), DMA (1.5 mL), H2O (0.5 mL), and the reaction mixture was stirred at 80 oC for 24 hrs. Upon completion of the reaction, the reaction mixture was directly purified by flash silica gel column chromatography using petroleum ether/ethyl acetate as eluent toafford the pure products.

Reference： [1]Tetrahedron Letters,2019,vol. 60

86
[ 32111-21-0 ]
[ 4261-42-1 ]
C₂₅H₂₂N₂O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium hydroxide; In water; at 50℃; for 16h;Inert atmosphere; Irradiation;	Under a nitrogen atmosphere, dissolve isoorientin (0.1 mmol), <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (0.4 mmol), and potassium hydroxide (0.2 mmol) in water (1 mL). After addition, the reaction The material was placed at 50 C, and the reaction was irradiated at 310 nm for 16 hours. The reaction was quenched with dilute hydrochloric acid (1N). The aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The organic phases were combined, followed by water and saturated table salt. Washed with water, dried over anhydrous sodium sulfate, concentrated and column chromatography to obtain 3-aryl flavonoid derivative (34.7 mg, 66% yield).

Reference： [1]Patent: CN111039910,2020,A .Location in patent: Paragraph 0072-0074

87
C₂₇H₃₃BN₂O₄ [ No CAS ]
[ 32111-21-0 ]
C₂₅H₂₄N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; toluene; at 80℃; for 12h;Sealed tube; Inert atmosphere;	To a 7-mL screw-cap tube containing a magnetic stirring bar were added 1b (19.9 mg, 43.2mumol), <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (13.5 mg, 65.6 mumol, 1.5 equiv), Pd(dppf)Cl2·CH2Cl2 (3.7 mg, 4.5 mumol,10 mol%), and K2CO3 (121 mg, 876 mumol, 20 equiv). The vessel was filled with nitrogen, andthen dry toluene (434 muL) and degassed H2O (434 muL) were added. The mixture was stirred at80 C for 12 h. After cooling to room temperature, EtOAc and H2O were added and the phaseswere separated. The aqueous phase was extracted with EtOAc. The organic phases werecombined, washed with brine, dried over Na2SO4, filtrated, and concentrated under reducedpressure. The residue was subjected to preparative thin layer chromatography (PTLC,CHCl3/MeOH = 20:1) to afford 1o (13.8 mg, 77% yield).

Reference： [1]Chem,2020,vol. 6,p. 985 - 993

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[ 32111-21-0 ] Synthesis Path-Upstream 1~9

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