[ CAS No. 91983-26-5 ] {[proInfo.proName]}

Name: 91983-26-5|4-(Cyanomethyl)benzeneboronic acid|98%
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Quality Control of [ 91983-26-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 91983-26-5 ]

Product Details of [ 91983-26-5 ]

CAS No. :	91983-26-5	MDL No. :	MFCD01632200
Formula :	C₈H₈BNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YKVMTTIYBSVPEQ-UHFFFAOYSA-N
M.W :	160.97	Pubchem ID :	2773342
Synonyms :

Calculated chemistry of [ 91983-26-5 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	45.79
TPSA :	64.25 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.94 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.48
Log Po/w (WLOGP) :	-0.57
Log Po/w (MLOGP) :	-0.03
Log Po/w (SILICOS-IT) :	-0.45
Consensus Log Po/w :	-0.11

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.38
Solubility :	6.74 mg/ml ; 0.0418 mol/l
Class :	Very soluble
Log S (Ali) :	-1.4
Solubility :	6.43 mg/ml ; 0.0399 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.77
Solubility :	2.75 mg/ml ; 0.0171 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.52

Safety of [ 91983-26-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P270-P271-P280-P301+P312+P330-P302+P352+P312+P362+P364-P304+P340+P312-P305+P351+P338+P337+P313-P501	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 91983-26-5 ]

* 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 [ 91983-26-5 ]
Downstream synthetic route of [ 91983-26-5 ]

[ 91983-26-5 ] Synthesis Path-Upstream 1~2

1
[ 91983-26-5 ]
[ 14191-95-8 ]

Reference： [1] Polymer, 2017, vol. 126, p. 291 - 295

2
[ 91983-26-5 ]
[ 90111-58-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 5, p. 1843 - 1852
[2] Tetrahedron, 1963, vol. 19, p. 821 - 826

[ 91983-26-5 ] Synthesis Path-Downstream 1~66

1
[ 64-17-5 ]
[ 91983-26-5 ]
[ 92243-74-8 ]

Reference： [1]Tetrahedron,1963,vol. 19,p. 821 - 826

2
[ 68162-47-0 ]
[ 151-50-8 ]
[ 91983-26-5 ]

Reference： [1]Tetrahedron,1963,vol. 19,p. 821 - 826

3
[ 91983-26-5 ]
[ 90111-58-3 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1843 - 1852
[2]Tetrahedron,1963,vol. 19,p. 821 - 826

5
[ 862730-04-9 ]
[ 91983-26-5 ]
2-(4-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃;	Synthesis of 2-(4-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)acetonitrile (BA45); A solution of (4-Cyanomethylphenyl)boronic acid (18 mg, 0.11 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (30 mg, 0.10 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80 C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H20:0.1% TFA) to yield BA45. ESI-MS (M+H)+ m/z calcd 293.1, found 293.1.

Reference： [1]Patent: US2007/293516,2007,A1 .Location in patent: Page/Page column 15; 19

6
[ 91983-26-5 ]
[ 7306-68-5 ]
[ 885594-56-9 ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 150℃; for 0.416667h;Microwave irradiation;	A solution of the N-protected chloropurine (0.27 g, 1.12 mmol), 4- cyanomethylphenylboronic acid (0.22 g, 1.37 mmol), 2M K2CO3 aq. (1.4 ml, 2.8 mmol) and Pd(PPh3)4 (0.03 g, 2.5 mol%) in DME (4 ml) was irradiated in a microwave reactor at 15O0C for 25 minutes. The organic layer was absorbed onto silica gel and purified by flash column chromatography, eluting 50% EtOAc- hexanes, to give a yellow solid (0.25 g, 70%). LC/MS (LCTl): R4 5.84 [M+H- THP]+ 236.
70%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 150℃; for 0.416667h;Microwave irradiation;	EXAMPLE 8; (4-(9/-/-purin-6-yl)phenyl)acetonitrile; 8A. (4-(9-(Tetrahvdropyran-2-yl)-9H-purin-6-yl)phenyl)acetonitrile <n="114"/>A solution of the N-protected chloropurine (0.27 g, 1.12 mmol), 4- cyanomethylphenylboronic acid (0.22 g, 1.37 mmol), 2M K2CO3 aq. (1.4 ml, 2.8 mmol) and Pd(PPh3)4 (0.03 g, 2.5 mol%) in DME (4 ml) was irradiated in a microwave reactor at 15O0C for 25 minutes. The organic layer was absorbed onto silica gel and purified by flash column chromatography, eluting 50% EtOAc-hexanes, to give a yellow solid (0.25 g, 70%). LC/MS (LCT1): Rt 5.84 [M+H-THP]+ 236.

Reference： [1]Patent: WO2006/46023,2006,A1 .Location in patent: Page/Page column 112
[2]Patent: WO2007/125315,2007,A2 .Location in patent: Page/Page column 111-112
[3]Journal of Medicinal Chemistry,2007,vol. 50,p. 2289 - 2292

7
[ 91983-26-5 ]
[ 885594-57-0 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2289 - 2292
[2]Patent: WO2007/125315,2007,A2

8
[ 91983-26-5 ]
2-(4-(9H-purin-6-yl)phenyl)ethylamine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2289 - 2292
[2]Patent: WO2007/125315,2007,A2

9
[ 393088-42-1 ]
[ 91983-26-5 ]
[ 807654-32-6 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; copper diacetate;molecular sieve; In dichloromethane;	Step A: {4-[(5,5-Dioxido-2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,2,4]benzothiadiazin-7-yl)oxy]phenyl}acetonitrile [0178] A suspension composed of 1.15 g (4.77 mmol) of 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c]-[1,2,4]benzothiadiazin-7-ol 5,5-dioxide, 1.00 g (6.21 mmol) of [4-(cyanomethyl)phenyl]-boronic acid, 1.3 g (7.15 mmol) of copper(II) acetate, 1.16 ml (14.31 mmol) of pyridine and about 500 mg of 4 molecular sieve in 200 ml of methylene chloride is stirred overnight. The reaction mixture is diluted by adding a further 100 ml of methylene chloride and the suspension is filtered. The filtrate is concentrated and then directly placed on a silica column which is eluted with a methylene chloride/methanol 99/1 system. The fractions containing the expected product are combined and evaporated, and the residue is taken up in a small amount of ethyl ether. After filtering off the solid, the title product is obtained in the form of beige powder. [0179] Melting point: 156-158 C.

Reference： [1]Patent: US2004/254161,2004,A1 .Location in patent: Page 10

10
[ 138500-86-4 ]
[ 91983-26-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium periodate; ammonium acetate; In water; acetone; at 20℃; for 2h;	Preparation of 4-(cyanomethyl)-phenylboronic acid. Using the method of Coutts, S. J., et al., Tetrahedron Lett., 35, 5109-5112 (1994), 4-(cyanomethyl)-phenylboronic acid, pinacol ester (25.0 g, 0.103 mol) was dissolved in acetone (500 ML) and water (27 ML).To this solution, 1N aqueous ammonium acetate was added (256 ML), followed by NalO4 (66.9 g, 0.300 mol).The turbid mixture was stirred under nitrogen for 2 h at room temperature to afford a thicker suspension.The reaction mixture was filtered and the filter cake was washed with acetone (330 ML) and water (150 ML).The filtrated was concentrated to a solid that was suspended in water (30 ML) and filtered.The filtrate was discarded.The combined collected solids were slurried in acetone (200 ML) and filtered.The filtrate was concentrated and the residue was dissolved in acetone (100 ML).A small amount of acetone-insoluble material was removed by filtration.The combined filtrates were concentrated to provide the intermediate title compound (18.9 g, 114%). 1H NMR (d6-acetone, 300 MHz) revealed the presence of H2O in this lot: delta7.90 (d, 2H, J=8.1), 7.38 (d, 2H, J=8.1), 7.25 (br, s, 2H), 3.97 (s, 2H). Preparation of Final Title Compound.

Reference： [1]Patent: US2003/225266,2003,A1 .Location in patent: Page 23

11
[ 305444-83-1 ]
[ 91983-26-5 ]
[ 305445-16-3 ]

Yield	Reaction Conditions	Operation in experiment
30%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃;	Scheme VI, step A': [2-fluoro-2-(4-iodophenyl)propyl][(methylethyl)sulfonyl]amine (500 mg, 1.3 mmol, prepared in example 1), 4-phenylacetonitrile boronic acid (193 mg, 1.4 mmol), potassium carbonate (193 mg, 1.4 mmol), tetrakis(triphenyl phosphine)palladium(0) (75 mg, 0.65 mmol), dioxane/water (30 mL, 3:1) were mixed together in a 100 mL single neck flask and stirred at 90 C. over night. In the morning, the reaction was cooled to room temperature and poured into H2O and the desired product was extracted with ethyl acetate. The organic layer was backwashed once with H2O, dried over K2CO3, and concentrated under reduced pressure to yield a viscous oil. This material was purified via silica gel chromatography employing the Chromatotron and using a 2000 micron rotor while eluting with a solvent of hexane/ethyl acetate 7:3 to yield the title compound (143 mg, 30%) as a yellow solid. Material was recrystallized from ethyl acetate-hexane 1:1. M.P. 155-157 C. Ion spray M.S. 373 (M*-1).Calculated for C20H23N2O2SF: Theory: C 64.15, H 6.19, N 7.48. Found: C 63.91, H 5.96, N 7.37.

Reference： [1]Patent: US7034045,2006,B1 .Location in patent: Page/Page column 44-45

12
[ 860625-21-4 ]
[ 91983-26-5 ]
[ 1201406-34-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In 1,4-dioxane; methanol; water;	Example 125 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-{4-[2-(methylamino)ethyl]phenyl}-1H-indole-7-carboxamide To a solution of 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (200 mg, 0.48 mmol) in dioxane and H2O was added was added <strong>[91983-26-5][4-(cyanomethyl)phenyl]boronic acid</strong> (232 mg, 0.144 mmol), potassium carbonate (400 mg, 2.88 mmol), and tetrakis(triphenylphosphine)palladium (0) (30 mg, 0.048 mmol). The solution was stirred and heated in the microwave at 160 C. for 40 min. The reaction was diluted with EtOAc and H2O and filtered to obtain a yellow crystal as desired product. The solution was washed with brine and H2O and then EtOAc was concentrated. To the reside was added MeOH which precipitated the desired product and then washed again with MeOH to give 5-[4-(cyanomethyl)phenyl]-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide.
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 160℃; for 0.666667h;Microwave irradiation;	Example 125: 3-ri-(ethylsulfonv?-4-piperidinv?-5-f4-r2-(methylamino)ethyliPhenyl>- 1 H-indole-7-carboxamide; To a solution of 5-bromo-3-[1 -(ethy.sulfonyl)-4-piperidinyl]-1 H-indole-7-carboxamide (200 mg, 0.48 mmol) in dioxane and H2O was added was added [4- (cyanomethyl)phenyl]boronic acid (232 mg, 0.144 mmol), potassium carbonate (400 mg, 2.88 mmol), and tetrakis(triphenylphosphine)palladium (0) (30 mg, 0.048 mmol). The solution was stirred and heated in the microwave at 160Q C for 40 min. The reaction was diluted with EtOAc and H2O and filtered to obtain a yellow crystal as desired product. The solution was washed with brine and H2O and then EtOAc was concentrated. To the reside was added MEOH which precipitated the desired product and then washed again with MeOH to give 5-[4-(cyanomethyl)phenyl]-3-[1 -(ethylsulfonyl)-4-piperidinyl]-1 H-indole- 7-carboxamide.

Reference： [1]Patent: US2009/143372,2009,A1
[2]Patent: WO2007/5534,2007,A2 .Location in patent: Page/Page column 158

13
[ 919496-41-6 ]
[ 91983-26-5 ]
(4-(4-isopropyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl)-phenyl)-acetonitrile trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%		Example 57 (General Procedure I) [4-(4-lsopropyl-3,4,5,6-tetrahydro-2H-[1 ,2']bipyrazinyl-5'-yl)phenyl]acetonitrile, trifluoroacetate: 4-Cyanomethylphenylboronic acid (0.137 g, 0.85 mmol), 5-bromo-4-isopropyl-3,4,5,6-tetra- hydro-2H-[1 ,2']bipyrazinyl (0.242 g, 0.85 mmol), bistriphenylphosphinpalladium(ll)dichloride (0.035 g, 0.080 mmol) and a 1 N Na2CO3 solution in H2O (1 .7 ml_)) were mixed in acetonitril (2 ml_) under an atmosphere of nitrogen in a 5 ml_ microwave vessel. The reaction mixture was heated 600 seconds at 1200C in a microwave oven. The reaction mixture was evaporated and the residue was dissolved in a mixture of H2O and dichloromethane. The phases were separated and the aquoeus phase was extracted with dichloromethane (3 x 25 ml_). The organic extracts were combined and trifluoroacetic acid was added. The volatiles were evaporated and the residue was dissolved in MeOH and purified according to preparative HPLC Method B to give 35 mg (10 %) of the title compound.1H NMR (400 MHz, CDCI3) delta 1 .40 (d, J=6.57 Hz, 6H) 2.92-3.03 (m, 2H) 3.54-3.65 (m, 5H) 3.81 (s, 2H) 4.48 (d, J=13.64 Hz, 2H) 7.42 (d, J=8.08 Hz, 2H) 7.91 (d, J=8.08 Hz, 2H) 8.24 (s, 1 H) 8.55 (s, 1 H) 12.43-13.00 (m, 1 H). 13C NMR (400 MHz, CDCI3) delta 16.96, 23.78, 42.43, 47.56, 58.32, 118.13, 126.86, 128.92, 130.44, 130.50, 136.78, 139.24, 142.57, 152.99.

Reference： [1]Patent: WO2007/3604,2007,A2 .Location in patent: Page/Page column 97-98

14
potassium cyanide [ No CAS ]
[ 68162-47-0 ]
[ 91983-26-5 ]

Reference： [1]Tetrahedron,1963,vol. 19,p. 821 - 826
[2]Gmelin Handbuch der Anorganischen Chemie,Gmelin Handbook: B: B-Verb.13, 4.7.2.6, page 219 - 226

15
[ 846563-95-9 ]
[ 91983-26-5 ]
[4-(9-cyclopropyl-6-fluoro-3,4-dioxo-2,3,4,9-tetrahydroisothiazolo[5,4-b]quinolin-7-yl)phenyl]acetonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1272 - 1276

16
[ 91983-26-5 ]
[ 68162-46-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1272 - 1276

17
[ 1082066-23-6 ]
[ 91983-26-5 ]
[ 1082063-18-0 ]

Yield	Reaction Conditions	Operation in experiment
58%		Example 16m: {4-[4-(l-Phenyl-lH-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H- [ 1 ,2']bipyrazinyl-3 '-yl] -phenyl} -acetonitrile hydrochlorideStir together 3'-chloro-4-(l-phenyl-lH-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro- 2H-[l,2']bipyrazinyl (177 mg, 0.50 mmol), <strong>[91983-26-5]4-(cyanomethyl)benzene boronic acid</strong> (97 mg, 0.60 mmol), potassium carbonate (166 mg, 1.20 mmol) and tetrakis(triphenylphosphine) palladium(O) (0.006 g, 0.003 mmol) and water (1 mL), in N,N-dimethylacetamide (2 mL) at room temperature under nitrogen, then heat at 1200C for 3 hr. Cool to room temperature, add water (20 mL) and extract with DCM (3 x 20 mL). Pass the combined DCM extracts through an 1ST Phase Separator Frit, concentrate and purify (silica gel chromatography, eluting with 5:95 to 15:85 methanol:DCM). Dry in a vacuum oven over night, then further purify by low pH reverse phase HPLC. Form the free base by passing through an SCX-2 ion exchange cartridge washing with methanol then eluting with 2 M ammonia in methanol and concentrate. Dissolve the solid in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize to give the title compound as a bright yellow solid (136 mg, 58%). MS (ES): m/z = 436 [M+H]+.

Reference： [1]Patent: WO2008/141020,2008,A1 .Location in patent: Page/Page column 170

18
[ 1082066-21-4 ]
[ 91983-26-5 ]
[ 1082063-54-4 ]

Yield	Reaction Conditions	Operation in experiment
		Example 43m: {4-[4-(l,5-Dimethyl-lH-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H- [ 1 ,2']bipyrazinyl-3 '-yl] -phenyl} -acetonitrile hydrochloride <n="187"/>--186-Stir 3'-chloro-4-(l,5-dimethyl-lH-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H- [l,2']bipyrazinyl (921 mg, 3.00 mmol), potassium carbonate (996 mg, 7.20 mmol), (4- cyanomethyl benzene) boronic acid (579 mg, 3.60 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.017 g, 0.015 mmol) in N,N- dimethylacetamide (6 mL). Add water (3 mL), degas for 5 min., and then heat at 120 0C for 24 hr. Purify by SCX-2 chromatography washing with methanol then eluting with 2 M ammonia in methanol. Further purify (silica gel chromatography, eluting with 0: 100 to 20:80 methanol: DCM), to give the free base as a yellow solid (1.24 g, 100%). MS (ES): m/z = 388 [M+H]+. Prepare the HCl salt as in Example 41 to give the title compound (93%). MS (ES): m/z = 388 [M+H].

Reference： [1]Patent: WO2008/141020,2008,A1 .Location in patent: Page/Page column 185-186

19
[ 1123302-10-2 ]
[ 91983-26-5 ]
[ 1123301-49-4 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ISOPROPYLAMIDE; water; at 110℃; for 18h;	Dissolve 1 -methyl- lH-pyrazole-4-sulfonic acid [2-(3'-chloro-2,3,5,6-tetrahydro- [l,2']bipyrazinyl-4-yl)-ethyl] -methyl-amide (0.250 g, 0.625 mmol) in DMA-H2O (or DME:H2O) (6 mL; 3: 1 v/v, previously degassed with nitrogen). Add A- cyanomethylphenyl boronic acid (0.121 g, 0.750 mmol), potassium carbonate (0.207 g, 1.500 mmol) and tetrakis(triphenylphosphine)palladium (0.036 g, 0.031 mmol). Stir the reaction mixture at 1100C for 18 hr. Cool and dilute with ethyl acetate and water. Extract the aqueous layer with ethyl acetate and combine the organic layers. Dry the combined organic layers over sodium sulfate, filter, and concentrate. Purify by SCX chromatography, eluting with dichloromethane, dichloromethane:methanol 1 : 1, methanol, and IN ammonia in methanol. Purify by silica gel chromatography eluting with hexanes: acetone 1: 1 to afford the free base of the title compound (0.214 g, 71% yield). Prepare the hydrochloride salt by dissolving the freebase (0.214 g) in acetonitrile and adding IN aqueous hydrochloric acid (0.489 mL, 0.489 mmol). Stir for 1 hr. at room temperature. Remove the organics and lyophilize the remaining aqueous portion to afford the title compound (0.212 g). MS ES: m/z = 481 [M+H]+.

Reference： [1]Patent: WO2009/29439,2009,A1 .Location in patent: Page/Page column 35

20
[ 91983-26-5 ]
5-bromothiophene-2-sulphonic acid tert-butylamide [ No CAS ]
[ 1158786-86-7 ]

Yield	Reaction Conditions	Operation in experiment
40%	With sodium carbonate;2'-(dimethylamino)-2-biphenyl-palladium (II) chloride dinorbornylphosphine; In ethanol; water; toluene; at 80℃; for 18h;	5-Bromo-thiophene-2-sulfonic acid tert.-butylamide (0.6 g) was suspended in toluene (5 mL) under an Ar-atmosphere. To the suspension (4-cyanomethylphenyl)boronic acid (486 mg), Na2CO3 (533 mg), water (2.5 ml) and EtOH (2.5 mL) was added. To this suspension 2'-(dimethylamino)-2-biphenyl-palladium (II) chloride dinorbornylphosphine complex (23 mg) was added and the mixture was stirred for 18 h at 80 C. After that the suspension was cooled to 25 C., evaporated to of the original volume and treated with EtOAc (30 mL). The organic layer was washed with aqueous HCl (1N, 10 mL) and brine. The organic layer was dried over Na2SO4, filtrated and evaporated to dryness. The crude material was purified by flash chromatography (eluent CH2Cl2, 2N NH3 in methanol) to yield 5-(4-cyanomethyl-phenyl)-thiophene-2-sulfonic acid tert-butylamide (268 mg, 40%) as a light yellow solid. [M-H]-=333.1

Reference： [1]Patent: US2009/143439,2009,A1 .Location in patent: Page/Page column 26

21
[ 402-43-7 ]
[ 91983-26-5 ]
[ 871252-44-7 ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 8163 - 8172

22
[ 328-70-1 ]
[ 91983-26-5 ]
(3′,5′-bis(trifluoromethyl)biphenyl-4-yl)acetonitrile [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 8163 - 8172

23
[ 91983-26-5 ]
[ 19524-06-2 ]
[ 112170-33-9 ]

Reference： [1]Angewandte Chemie - International Edition,2010,vol. 49,p. 3757 - 3761
[2]Chemistry - A European Journal,2017,vol. 23,p. 10017 - 10022

24
[ 1134915-78-8 ]
[ 1246382-93-3 ]
[ 91983-26-5 ]
[ 1246382-95-5 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: {3'-Chloro-4'-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-propyl]-biphenyl-4-yl}-acetonitrile In analogy to Example 150, step 2, 5-[2-(4-bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1-methyl-1H-pyridin-2-one (Example 165, step 3) was reacted with 4-cyanomethylphenylboronic acid to give the title compound as an off-white solid. MS (m/e)=461.3 [M+H+].

Reference： [1]Patent: US2010/249139,2010,A1

25
[ 1134915-79-9 ]
[ 1246382-93-3 ]
[ 91983-26-5 ]
[ 1246382-97-7 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: {3'-Chloro-4'-[3,3,3-trifluoro-2-hydroxy-2-(6-methoxy-pyridin-3-yl)-1-methyl-propyl]-biphenyl-4-yl}-acetonitrile In analogy to Example 150, step 2, 3-(4-bromo-2-chloro-phenyl)-1,1,1-trifluoro-2-(6-methoxy-pyridin-3-yl)-butan-2-ol (Example 175, step 3) was reacted with 4-cyanomethylphenylboronic acid to give the title compound as a colorless foam. MS (m/e)=461.3 [M+H+]

Reference： [1]Patent: US2010/249139,2010,A1

26
8-bromo-5-methyl-[1,2,4]-triazolo[4,3-a]quinolin-1-one [ No CAS ]
[ 91983-26-5 ]
C₁₉H₁₄N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 5133 - 5138

27
[ 1246685-13-1 ]
[ 91983-26-5 ]
[ 1246685-14-2 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 80℃; for 0.333333h;Sealed tube;	mixture of 5-[2-(4-bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one (Example 73 step 6, 40 mg), dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) (10 mg), Cs2CO3 (84 mg) and (4-cyanomethylphenyl)boronic acid (CAS Reg. No. 91983-26-5, 27 mg) in dioxane (1 ml) and water (0.1 ml) was heated at 80 C. for 20 min in a sealed tube. The mixture was acidified with HCOOH and then purified by prep. HPLC (C18-column, solvent gradient 30-98%) to give the title compound (27 mg). MS (m/e)=514.2 [M+H+].

Reference： [1]Patent: US2010/249124,2010,A1 .Location in patent: Page/Page column 53

28
[ 22753-30-6 ]
[ 91983-26-5 ]
[ 1192344-20-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6390 - 6401

29
[ 22753-30-6 ]
[ 91983-26-5 ]
[ 1192343-96-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6390 - 6401

30
[ 1270930-36-3 ]
[ 91983-26-5 ]
[ 1270930-44-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 734 - 737

31
[ 1270930-35-2 ]
[ 91983-26-5 ]
[ 1270930-45-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 734 - 737

32
[ 1270930-35-2 ]
[ 91983-26-5 ]
[ 1270930-80-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 734 - 737

33
[ 1065181-82-9 ]
[ 91983-26-5 ]
[ 1065177-11-8 ]

Yield	Reaction Conditions	Operation in experiment
42%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 100℃; for 0.25h;Inert atmosphere; Microwave irradiation;	Example 65:S-^^CyanomethylJphenylJ-S-tiji -dioxidotetrahydro^H-thiopyran^-ylJ-IH-indole-?- carboxamide.A mixture of 5-bromo-3-(1 ,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1 H-indole-7- carboxamide (60 mg, 0.162 mmol), <strong>[91983-26-5][4-(cyanomethyl)phenyl]boronic acid</strong> (52.0 mg, 0.323 mmol) and K2CO3 (67.0 mg, 0.485 mmol) in 1 ,4-dioxane (0.18 ml.) and water (0.08 ml.) was degassed in a Biotage microwave vial for 10 min. PdCI2(dppf) (1 1.83 mg, 0.016 mmol) was added, the vial sealed, and the reaction heated at 100 0C for 5 min (microwave reaction). EtOAc (3 ml.) and water (1 ml.) were added, the layers were separated, and the aqueous layer was extracted with EtOAc (4 x 2 ml_). The combined organic layers were washed with saturated NaCI (1 x 2 ml_), dried (Na2SO4), and concentrated under a stream of nitrogen at 50 0C. Recovered 27 mg (42%) of the title compound. LC/MS: m/z 409.1 (M+H), Rt 1.61 min.

Reference： [1]Patent: WO2008/118724,2008,A1 .Location in patent: Page/Page column 144

34
[ 91983-26-5 ]
[ 1423167-21-8 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1843 - 1852

35
[ 91983-26-5 ]
[ 1423167-46-7 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1843 - 1852

36
[ 91983-26-5 ]
[ 1423167-25-2 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1843 - 1852

37
[ 91983-26-5 ]
[ 1423167-34-3 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1843 - 1852

38
[ 1607590-93-1 ]
[ 91983-26-5 ]
[ 1607590-89-5 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; acetonitrile; at 160℃; for 0.166667h;Microwave irradiation;	A mixture of <strong>[91983-26-5][4-(cyanomethyl)phenyl]boronic acid</strong> (from Aldrich, 9.3 mg, 0.058 mmol), 8-iodo-7-methylimidazo[1,2-a]thieno[3,2-e]pyrazine (12 mg, 0.038 mmol), and potassium carbonate (16 mg, 0.12 mmol), in acetonitrile (0.6 mL) and water (0.2 mL) was degassed. Into the mixture was added tetrakis(triphenylphosphine)palladium(0) (2.2 mg, 0.0019 mmol). The reaction mixture was heated at 160 C. for 10 min in a microwave reactor. The reaction was diluted with methanol, filtered. The filtrate was purified by prep-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product. LCMS calculated for C17H13N4S (M+H)+: m/z=305.1. Found: 305.0. 1H NMR (CDCl3, 400 MHz) delta 9.01 (1H, s), 7.55 (4H, m), 7.49 (1H, d, J=6.0 Hz), 7.14 (1H, d, J=6.0 Hz), 3.93 (2H, s), 2.48 (3H, s) ppm.

Reference： [1]Patent: US2014/121198,2014,A1 .Location in patent: Paragraph 0714; 0719

39
[ 1607591-63-8 ]
[ 91983-26-5 ]
[ 1607591-59-2 ]

Yield	Reaction Conditions	Operation in experiment
64%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In water; N,N-dimethyl-formamide; at 95℃; for 10h;Microwave irradiation; Inert atmosphere;	A microwave vial charged with 9-bromo-8-methylpyrazolo[1,5-c]thieno[2,3-e]pyrimidine (48.0 mg, 0.179 mmol), <strong>[91983-26-5][4-(cyanomethyl)phenyl]boronic acid</strong> (from Aldrich, 51.9 mg, 0.322 mmol), sodium carbonate (47.4 mg, 0.448 mmol), [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (15 mg, 0.018 mmol), DMF (1.3 mL) and water (0.13 mL) was purged with N2 and then stirred at 95 C. for 10 h. The reaction was diluted with ethyl acetate and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude was purified with prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (35 mg, 64%). LCMS calculated for C17H13N4S (M+H)+: m/z=305.1. Found: 305.0

Reference： [1]Patent: US2014/121198,2014,A1 .Location in patent: Paragraph 0790; 0797

40
[ 1607-57-4 ]
[ 91983-26-5 ]
[ 1609104-34-8 ]

Yield	Reaction Conditions	Operation in experiment
68%		The intermediate 2 were prepared according to the literature methods.31 The synthetic route of R-TPE is showed in Scheme 1. 1-Bromo-1,2,2-triphenylethene (1.74g, 5.2mmol) and <strong>[91983-26-5]4-(cyanomethyl)phenylboronic acid</strong> (1.00g, 6.2mmol) were dissolved in the mixture of toluene (40mL), Aliquat 336 (10 drops), and 2M potassium carbonate aqueous solution (10mL). The mixture was stirred at room temperature for 0.5h under Ar gas followed adding Pd(PPh3)4 (0.010g, 8.70×10-3mmol) and then heated to 90C for 24h. After that the mixture was poured into water and extracted three times with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the residue was chromatographed on a silica gel column with petroleum ether/CH2Cl2 (3:1 by volume) as eluent to give intermediate 1 (1.30g, 68% yield). 1H NMR (400MHz, CDCl3) delta (ppm): 3.65 (s, 2H, -CH2-), 6.98-7.06 (m, 10H, phenyl-H), 7.07-7.15 (m, 9H, phenyl-H); HRMS calcdfor C28H21N[M+H]+: 372.1752, found 372.1759. Elemental analysis calcdfor C28H21N: C, 90.53; H, 5.70; N, 3.77. Found: C, 90.37; H, 5.81; N, 3.69.

Reference： [1]Tetrahedron,2014,vol. 70,p. 3553 - 3559

41
3-iodo-4-methoxy-1-(1-methoxybutan-2-yl)-1H-pyrrolo[3,2-c]pyridine [ No CAS ]
[ 91983-26-5 ]
(4-(1-(1-methoxybutan-2-yl)-4-oxo-4,5-dihydro-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)acetonitrile [ No CAS ]

Reference： [1]Patent: EP2857400,2015,A1

42
3-iodo-4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-c]pyridine [ No CAS ]
[ 91983-26-5 ]
(4-(4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 1h;Microwave irradiation;	A) (4-(4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)acetonitrile [0468] To a solution of 3-iodo-4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-c]pyridine (20.0 mg) obtained in Step A of Example 16 in DMF (2 mL)/ water (0.20 mL) were added <strong>[91983-26-5](4-(cyanomethyl)phenyl)boronic acid</strong> (13.5 mg), tetrakis(triphenylphosphine)palladium(0) (6.45 mg) and potassium carbonate (15.4 mg). The reaction mixture was stirred under microwave irradiation at 130C for 1 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate =4/1 to 2/1) to give the title compound (12.0 mg) as a white solid. 1H NMR (300 MHz, DMSO-d6) delta 1.89-1.94 (2H, m), 2.01-2.15 (2H, m), 3.54-3.61 (2H, m), 3.90 (3H, s), 3.99-4.03 (2H, m), 4.05 (2H, s), 4.60-4.75 (1H, m), 7.30-7.37 (2H, m), 7.61-7.68 (4H, m), 7.81 (1H, d, J = 6.1 Hz)

Reference： [1]Patent: EP2857400,2015,A1 .Location in patent: Paragraph 0468

43
3-iodo-4-methoxy-1-(1-methoxybutan-2-yl)-1H-pyrrolo[3,2-c]pyridine [ No CAS ]
[ 91983-26-5 ]
(4-(4-methoxy-1-(1-methoxybutan-2-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20.2 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 0.5h;Microwave irradiation;	A) (4-(1-(1-methoxybutan-2-yl)-4-oxo-4,5-dihydro-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)acetonitrile [0455] To a solution of 3-iodo-4-methoxy-1-(1-methoxybutan-2-yl)-1H-pyrrolo[3,2-c]pyridine (50.0 mg) obtained in Step A-2 of Example 17 in DMF (2 mL)/ water (0.20 mL) were added <strong>[91983-26-5](4-(cyanomethyl)phenyl)boronic acid</strong> (33.8 mg), tetrakis(triphenylphosphine)palladium(0) (15.9 mg) and potassium carbonate (38.3 mg). The reaction mixture was stirred under microwave irradiation at 130C for 30 min. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (20.2 mg). 1H NMR (300 MHz, DMSO-d6) delta 0.67-0.77 (3H, m), 1.87 (2H, quin, J = 7.2 Hz), 3.20 (3H, s), 3.61-3.71 (1H, m), 3.72-3.83 (1H, m), 3.90 (3H, s), 4.06 (2H, s), 4.52-4.69 (1H, m), 7.26 (1H, d, J= 6.1 Hz), 7.35 (2H, d, J= 8.0 Hz), 7.58-7.68 (3H, m), 7.78 (1H, d, J = 6.1 Hz). MS (ESI+): [M+H]+ + 350.2. MS (ESI+), found: 350.1.

Reference： [1]Patent: EP2857400,2015,A1 .Location in patent: Paragraph 0455

44
3-iodo-4-methoxy-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[3,2-c]pyridine [ No CAS ]
[ 91983-26-5 ]
(4-(4-methoxy-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16.8 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 0.5h;Microwave irradiation;	A) (4-(4-methoxy-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl)phenyl)acetonitrile [0461] To a solution of 3-iodo-4-methoxy-1-(tetrahydrofuran-3-yl)-1H-pyrrolo[3,2-c]pyridine (50.0 mg) obtained in Step A of Example 22 in DMF (2 mL)/water (0.20 mL) were added <strong>[91983-26-5](4-(cyanomethyl)phenyl)boronic acid</strong> (35.1 mg), tetrakis(triphenylphosphine)palladium(0) (16.8 mg) and potassium carbonate (40.2 mg). The reaction mixture was stirred under microwave irradiation at 130C for 30 min. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (16.8 mg). MS (ESI+): [M+H]+ 334.2. MS (ESI+), found: 334.1.

Reference： [1]Patent: EP2857400,2015,A1 .Location in patent: Paragraph 0461

45
1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate [ No CAS ]
[ 91983-26-5 ]
(4-(1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
107 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 1h;Microwave irradiation;	A) (4-(1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)acetonitrile [0527] To a solution of 1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate (150 mg) obtained in Step C of Example 35 in DMF (4 mL)/ water (0.40 mL) were added <strong>[91983-26-5](4-(cyanomethyl)phenyl)boronic acid</strong> (156 mg), tetrakis(triphenylphosphine)palladium(0) (42.4 mg) and potassium carbonate (101 mg). The reaction mixture was stirred under microwave irradiation at 130C for 1 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (107 mg). 1H NMR (300 MHz, DMSO-d6) delta 4.04 (3H, s), 4.15 (2H, s), 7.04 (1H, d, J = 5.7 Hz), 7.49-7.54 (3H, m), 7.69-7.83 (2H, m), 8.00 (2H, d, J = 8.0 Hz), 8.07 (1H, d, J = 6.1 Hz). MS (ESI+) : [M+H]+ 377.1. MS (ESI+), found: 377.1.

Reference： [1]Patent: EP2857400,2015,A1 .Location in patent: Paragraph 0527

46
[ 91983-26-5 ]
C₂₈H₃₀N₄O₄ [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 120,p. 160 - 169

47
[ 91983-26-5 ]
1-azido-4-cyanomethylbenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium azide; copper diacetate; In water; acetonitrile; at 20℃;	General procedure: To the solution of particular phenylboronic acid (1eq) in acetonitrile: water 1:1 was added. Cu(OAc)2 (10mol%) and NaN3 (1.5 eq) and allowed to react at room temperature on magnetic stirrer. Upon completion, the reaction mixture was extracted with ethylacetate and water. The organic layer was concentrated on rota evaporated to furnish the corresponding azide in almost 98% yield and of sufficient purity to be used in the subsequent reactions (Scheme 2).

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 120,p. 160 - 169

48
1-(2-{4-(dimethylamino)piperidin-1-yl}ethyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
[ 91983-26-5 ]
2-[4-(4-amino-1-{2-[4-(dimethylamino)piperidin-1-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl]acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.8%	With palladium diacetate; potassium carbonate; triphenylphosphine; In 1,4-dioxane; water; at 120℃; for 0.5h;Microwave irradiation;	To a solution of I -[2-[4-(dimethylamino)-1 -piperidyl]ethyl]-3-iodo-pyrazolo[3,4- d]pyrimidin-4-amine (50 mg, 0.1205 mmol) in dioxane/water (4.5/0.5 ml) was added 4- (Cyanomethyl)benzeneboronic acid, (1 eq., 29.1 mg, 0.181 mmol), potassiumcarbonate (1.5 eq., 25.0 mg, 0.181 mmol) and triphenylphosphine (20 mol %, 9.5 mg) followed by palladium acetate (5 mol %) and the mixture heated in the microwave at 120 C for 30 mins. The mixture was concentrated in vacuo and purified by column chromatography, MeOH/DCM (5-10 % then 20 drops of NEt3 per 100 ml) to give a cream solid, (41.8 mg, 0.1034 mmol, 85.8 %). 1H NMR (500 MHz, MeOD) O 8.27 (s,11-1), 7.79-7.70 (m, 2H), 7.59 (d, J = 8.3, 2H), 4.56 (t, J = 6.4, 2H), 4.03 (s, 2H), 3.18 (d, J = 5.8, 2H), 3.04-2.93 (m, 3H), 2.74 (s, 6H), 2.17 (dd, J 15.1, 6.9, 2H), 1.99 (d, J12.8, 2H), 1.61 -1.51 (m, 2H); 13C NMR (126 MHz, MeOD) 6 158.49 (C), 155.47 (CH), 154.36 (C), 144.35 (C)1 132.22 (C), 128.84 (2x CH), 128.70 (2x CH), 117.95 (C),110.00 (C), 97.74 (C), 63.27 (CH), 55.84 (CH2), 51.39 (2x CH2), 44.11 (CH2), 39.27 (2xCH3), 26.32 (2x CH2), 21.98 (CH2); MS (ES +ve) [M+HJ: 405.0; HRMS (ES +ve), C22H29N8 (M-i-H): calculated 405.25097, found 405.24950.

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 4697 - 4710
[2]Patent: WO2016/185160,2016,A1 .Location in patent: Page/Page column 96; 97

49
[ 1046864-84-9 ]
[ 91983-26-5 ]
C₄₀H₃₄N₄O₆S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%		Compound 8 (1.00 g, 1.5189 mmol) was added to a 250 ml 2-neck round bottom flask,4- (Cyanomethyl) benzeneboronic acid (0.61 g, 3.7971 mmol) was added to 150 ml of toluene and stirred. After raising the temperature to ~ 50 C, Pd (0) (0.52 mg, 3 mol%) was added I put it. Stir for a few minutes. And 2M aq.K2CO3 And the temperature was raised to 90 C and stirred. After the reaction,The temperature was lowered to room temperature, the solvent was evaporated under reduced pressure at 80 C, washed several times with water, and then recrystallized with MC / EtOH to obtain Compound 9 (yield: 83%).

Reference： [1]Patent: KR2015/85909,2015,A .Location in patent: Page/Page column 0150; 0158-0160

50
[ 91983-26-5 ]
(S)-2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acid [ No CAS ]
(2S)-2-(tert-butoxy)-2-{5-[4-(cyanomethyl)phenyl]-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl}acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 50 - 100℃;	General procedure: General Procedure for the preparation of examples XX- YY: To a mixture of (S)-2-(5- bromo-4-(4,4-dimethylpiperidin-l-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acid (1 - 5 eq., aryl boronic acid or ester (1 - 5 eq.) and CS2CO3 (2 - 3 eq.) in 1,4-dioxane and water (volume ratio 20 : 1 to 1 : 1) was added Pd(PPh3)4 (0.01 - 1 eq.). The mixture was flushed with nitrogen and then heated at 50 - 100C for 1 to 8 hours. The mixture was diluted with water and then extracted with EtOAc. The organic layers were combined, washed with brine, concentrated and the residue was purified by preparative HPLC to give the desired product.

Reference： [1]Patent: WO2017/6281,2017,A1 .Location in patent: Page/Page column 82

51
(S)-ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate [ No CAS ]
[ 91983-26-5 ]
ethyl (2S)-2-(tert-butoxy)-2-{5-[4-(cyanomethyl)phenyl]-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl}acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57.2%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In N,N-dimethyl-formamide; at 90℃; for 8h;Inert atmosphere;	(S)-Ethyl 2-(tert-butoxy)-2-(5-(4-(cyanomethyl)phenyl)-4-(4,4-dimethylpipe 2,6-dimethylpyridin-3-yl)acetate: A mixture of (S)-ethyl 2-(5-bromo-4-(4,4- dimethylpiperidin-l-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (0.02 g, 0.044 mmol), <strong>[91983-26-5](4-(cyanomethyl)phenyl)boronic acid</strong> (0.014 g, 0.088 mmol) and 2M Na2C03 (0.055 ml, 0.110 mmol) was degassed for 2 min. To this was added Pd(Ph3P)4 (5.07 mg, 4.39 mupiiotaomicron), degassed for 1 min and placed in pre-heated oil bath at 90 C. After 8 h, cooled and purified by prep-HPLC to afford (S)-ethyl 2-(tert-butoxy)-2-(5-(4- (cyanomethyl)phenyl)-4-(4,4-dimethylpiperidin-l-yl)-2,6-dimethylpyridin-3-yl)acetate (0.0098 g, 0.020 mmol, 45.4 % yield) as brown paste. LCMS (M+H) = 492.5.

Reference： [1]Patent: WO2017/6281,2017,A1 .Location in patent: Page/Page column 75

52
[ 91983-26-5 ]
(Z)-2-(4-(4-pyridyl)phenyl)-3-(5-(pyridin-4-yl) thiophen-2-yl)acrylonitrile [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 10017 - 10022

53
[ 91983-26-5 ]
(Z)-2,3-bis(4-(pyridin-4-yl)phenyl)acrylonitrile [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 10017 - 10022

54
[ 91983-26-5 ]
[ 14191-95-8 ]

Reference： [1]Polymer,2017,vol. 126,p. 291 - 295

55
[ 91983-26-5 ]
2,6-dichloro-N-(3-cyclopropyl-1H-pyrazol-5-yl)quinazolin-4-amine [ No CAS ]
2-(4-(6-chloro-4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)phenyl)acetonitrile [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 1224 - 1229

56
[ 1003-09-4 ]
[ 91983-26-5 ]
(4-thiophen-2-ylphenyl)-acetonitrile [ No CAS ]