[ CAS No. 70799-12-1 ] {[proInfo.proName]}

Name: 70799-12-1|4-((Dimethylamino)methyl)phenylboronic acid|97%
Brand: Ambeed
SKU: A177946
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Quality Control of [ 70799-12-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 70799-12-1 ]

SDS Specification

Alternatived Products of [ 70799-12-1 ]

Product Details of [ 70799-12-1 ]

CAS No. :	70799-12-1	MDL No. :	MFCD01319001
Formula :	C₉H₁₄BNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LRWRYAVXFZBFRJ-UHFFFAOYSA-N
M.W :	179.02	Pubchem ID :	22506610
Synonyms :

Calculated chemistry of [ 70799-12-1 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.33
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	53.74
TPSA :	43.7 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 :	No
Log Kp (skin permeation) :	-6.92 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.66
Log Po/w (WLOGP) :	-0.72
Log Po/w (MLOGP) :	0.38
Log Po/w (SILICOS-IT) :	-0.85
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) :	-1.51
Solubility :	5.54 mg/ml ; 0.031 mol/l
Class :	Very soluble
Log S (Ali) :	-1.15
Solubility :	12.6 mg/ml ; 0.0702 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.8
Solubility :	2.82 mg/ml ; 0.0158 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.43

Safety of [ 70799-12-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 70799-12-1 ]

* 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 [ 70799-12-1 ]
Downstream synthetic route of [ 70799-12-1 ]

[ 70799-12-1 ] Synthesis Path-Upstream 1~1

1
[ 688-74-4 ]
[ 6274-57-3 ]
[ 70799-12-1 ]

Reference： [1] Patent: WO2007/18941, 2007, A2, . Location in patent: Page/Page column 58

[ 70799-12-1 ] Synthesis Path-Downstream 1~43

1
[ 70799-12-1 ]
[ 480423-17-4 ]
[ 1030610-61-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 2h;	Intermediate 3: [4-(4-Bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)phenyl] methyl} - dimethylamineStep BStep A: [(4-{4-Bromo-1-[(4-methylphenyl)sulfonyl]-1 /-/-pyrrolo[2,3-6]pyridin-2- yl}phenyl)methyl]dimethylamine; {4-[(Dimethylamino)methyl]phenyl}boronic acid (157 mg, 0.6 mmol) and 4-bromo-2- iodo-1-[(4-methylphenyl)sulfonyl]-1 /-/-pyrrolo[2,3-6]pyridine (270 mg, 0.6 mmol), which was prepared according to WO2003000690, were dissolved in DME (2 ml.) and aqueous Na2CO3 (2 M, 0.2 ml_). The resulting solution and Pd(PPh3)4 (69.3 mg,0.06 mmol) were added to a microwave vial. After capping, the mixture was heated with SmithSynthesizer at 120 0C for 2 hours. The reaction mixture was filtered and washed with MeOH. Concentration in vacuo gave the residue, which was directly used for the Step B.

Reference： [1]Patent: WO2008/67119,2008,A2 .Location in patent: Page/Page column 29; 39
[2]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 1958 - 1963

2
[ 70799-12-1 ]
[ 1146633-69-3 ]
[ 1146944-32-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;nickel(II) chloride, nickel(II) bromide, bis(triphenylphosphine)nickel(II) chloride, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium; In 1,2-dimethoxyethane; ethanol; water; N,N-dimethyl-formamide;	EXAMPLE 1 3-Benzoxazol-2-yl-5-[4-(dimethylaminomethyl)phenyl]pyridin-2-amine 2M Sodium carbonate solution (0.4 ml) was added to a solution of 3-(benzoxazol-2-yl)-5-bromo-pyridin-2-amine (0.10 g), <strong>[70799-12-1][4-(dimethylaminomethyl)phenyl]boronic acid</strong> (0.075 g) and dichlorobis(triphenylphosphine)palladium (II) (0.003 g) in a mixture of 2:7:3:2 DMF:DME:water:ethanol (3 ml). The reaction mixture was heated at 160 C. for 7 mins in a 100 W microwave oven. The solvent was evaporated in a Genevac and NMP (1.8 ml) was added. The mixture was filtered and purified by X bridge preparative HPLC. There was thus obtained the title compound (0.021 g); Mass Spectrum: M+H+ 344, RT 2.82 min.

Reference： [1]Patent: US2009/118305,2009,A1

4
[ 70799-12-1 ]
[ 1186482-08-5 ]
[ 1186483-48-6 ]

Yield	Reaction Conditions	Operation in experiment
		Example 42 (4-{6-[2-(2,3-Difluoro-phenyl)-imidazo[4,5-d]pyridazin-5-ylmethyl]-pyridazin-3-yl}-benzyl)-dimethyl-amine (Compound 233) From 5-(6-chloro-pyridazin-3-ylmethyl)-2-(2,3-difluoro-phenyl)-5H-imidazo[4,5-d]pyridazine and 4-dimethylaminomethyl-phenylboronic acid following general procedure A. MS 458.2 (M+H+); H1 NMR (DMSO-d6): delta(ppm) 10.42 (s, 1H), 9.63 (s, 1H), 8.35-8.38 (m, 1H), 8.23-8.13 (m, 3H), 7.99-8.02 (m, 1H), 7.69-7.72 (m, 3H), 7.40-7.42 (m, 1H), 6.38 (s, 2H), 2.71 (s, 6H).

Reference： [1]Patent: US2009/226398,2009,A1

5
[ 70799-12-1 ]
[ 889939-26-8 ]
[ 942920-78-7 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 3973 - 4001

6
[ 70799-12-1 ]
[ 1251589-07-7 ]
[ 1251589-44-2 ]

Yield	Reaction Conditions	Operation in experiment
9%	With potassium carbonate; cesium fluoride;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 135℃; for 0.416667h;Inert atmosphere; Microwave irradiation;	To a mixture of compound 2174 (65 mg, 1 eq) in dioxane (1 mL) and water (0.5 mL) at RT is added 4-(N,N-dimethylaminomethyl)phenylboronic acid (35 mg, 1.5 eq), K2CO3 (55 mg, 3.0 eq) and CsF (60 mg, 3.0 eq). The mixture is degassed with a stream of Ar, then Pd(dppf)Cl2.CH2Cl2 (9.7 mg, 0.1 eq) is added. The mixture is heated in a Biotage microwave at 135 C. for 25 min, and then concentrated under reduced pressure. The residue is dissolved in AcOH and DMSO and purified by prep HPLC to give compound 2194 (6.7 mg, 9%).

Reference： [1]Patent: US2010/261714,2010,A1 .Location in patent: Page/Page column 50

7
[ 70799-12-1 ]
[ 1251582-03-2 ]
[ 1251589-80-6 ]

Yield	Reaction Conditions	Operation in experiment
2%	With potassium carbonate; cesium fluoride;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 150℃; for 0.5h;Inert atmosphere; Microwave iradiation;	To a mixture of compound 27b (Example 9) (65.6 mg, 0.157 mmol) in dioxane (1 mL) and water (0.4 mL) at RT is added 4-(N,N-dimethylaminomethyl)phenylboronic acid pinacol ester (42.2 mg, 0.236 mmol), K2CO3 (21.7 mg, 0.157 mmol) and CsF (71.6 mg, 0.472 mmol). The mixture is degassed with a stream of Ar, then Pd(dppf)Cl2.CH2Cl2 (11.5 mg, 0.016 mmol) is added. The mixture is heated in a Biotage microwave at 150 C. for 30 min, quenched with 0.1 mL AcOH and then concentrated under reduced pressure. The residue is dissolved in AcOH and DMSO and purified by prep HPLC to give compound 2213 (1.5 mg, 2%).

Reference： [1]Patent: US2010/261714,2010,A1 .Location in patent: Page/Page column 55

8
[ 70799-12-1 ]
[ 1251584-13-0 ]
[ 1251592-10-5 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; cesium fluoride;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 135℃; for 0.416667h;Microwave irradiation;	A mixture of compound 65b (50 mg, 0.128 mmol), 4-((N,N-dimethylaminomethyl) phenylboronic acid pinacol ester (67 mg, 0.256 mmol), Pd(dppf)Cl2 (9.7 mg, 0.013 mmol), K2CO3 (55.0 mg, 0.40 mmol) and CsF (40.4 mg, 0.27 mmol) in dioxane (2 mL) and H2O (0.5 mL) is allowed to stir for 1 min and is then heated in a microwave reaction vessel at 135 C. for 25 min. The mixture is concentrated under reduced pressure and the residue is diluted with AcOH/DMF (1.5/1.5) mL, filtered and purified by prep HPLC to give compound 3003 (17 mg, 74%).

Reference： [1]Patent: US2010/261714,2010,A1 .Location in patent: Page/Page column 91

9
[ 70799-12-1 ]
[ 1251581-87-9 ]
[ 1251589-82-8 ]

Yield	Reaction Conditions	Operation in experiment
35%	With potassium carbonate; cesium fluoride;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 135℃; for 0.416667h;Microwave irradiation;	To a mixture of compound 12b (37.9 mg, 1 eq), p-N,N-dimethylbenzylamine boronic acid (16.5 mg, 0.092 mmol) and dioxane (0.59 mL)/H2O (0.26 mL) (bubbled with Ar for 10 min.), is added K2CO3 (12.7 mg, 0.092 mmol) and cesium fluoride (42 mg, 0.28 mmol), followed by Pd(dppf)Cl2 (6.7 mg, 0.01 mmol). The mixture is heated in a microwave (135 C., 25 min.), then concentrated under reduced pressure. The residue is dissolved in AcOH and purified by prep HPLC to give compound 2214 (15 mg, 35%).Example 13

Reference： [1]Patent: US2010/261714,2010,A1 .Location in patent: Page/Page column 47

10
[ 70799-12-1 ]
[ 586-78-7 ]
[ 925920-79-2 ]

Yield	Reaction Conditions	Operation in experiment
		b. A solution of 4-bromo-nitro-benzene (113 g, 0.5586 mole) in toluene (2L) was heated under nitrogen to 80 - 85 0C. Pd(Ph3P)4 (25.8 g, 0.0223 mole) was added and stirred for 30 minutes, and then the aqueous solution of boronic acid (step a) was added, followed by addition of Na2CO3 (118.4 g, 1.1172 mole). The reaction was heated for 24 hours. The reaction mixture was allowed to reach room temperature and then transferred to a separatory funnel. The organic layer was separated and washed with water (1 L). The toluene layer was then treated with 1 N HCI (2 L). The aqueous layer was washed with diethyl ether (2 x 1 L), basified by addition of 50% aqueous EPO <DP n="60"/>NaOH. The precipitated solid was filtered and dried to give the coupled product as a yellow solid (107 g).

Reference： [1]Patent: WO2007/18941,2007,A2 .Location in patent: Page/Page column 58-59

11
[ 688-74-4 ]
[ 6274-57-3 ]
[ 70799-12-1 ]

Yield	Reaction Conditions	Operation in experiment
		a.; A solution of (4-bromobenzyl)dimethylarnine (120 g, 0.50 mole) in THF (2 L) was cooled to -78 0C and treated dropwise with n-BuLi (47 g, 0.728 mole). The reaction mixture was stirred for 1 hour and then butyl borate (194 g, 0.84 mole) was added dropwise. The reaction mixture was stirred for 1 hour, allowed to warm to 0 0C, and then quenched by the addition of water (1.5 L). The reaction mixture was washed with ether (2 x 1 L), and the aqueous layer taken on to the next step.

Reference： [1]Patent: WO2007/18941,2007,A2 .Location in patent: Page/Page column 58

12
[ 70799-12-1 ]
[ 1403257-55-5 ]
[ 1403254-70-5 ]

Yield	Reaction Conditions	Operation in experiment
29%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 4h;Inert atmosphere;	Example 16 Synthesis of 5-(Cyclohexyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4'-((dimethylamino)methyl)-4-methyl-[1,1'-biphenyl]-3-carboxamide To a stirred solution of 5-bromo-3-(cyclohexyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methylbenzamide (1 equiv.) and <strong>[70799-12-1](4-((dimethylamino) methyl)phenyl)boronic acid</strong> (1.2 equiv.) in dioxane/water mixture (5 mL+1 mL), Na2CO3 (3.6 equiv.) was added and the solution was purged with argon for 15 min. Then Pd (PPh3)4 (0.1 equiv.) was added and solution was purged again for 10 min. Reaction mixture was heated at 100 C. for 4 h. On completion, the mixture was diluted with water and extracted with 10% MeOH/DCM. Combined organic layers were dried over Na2SO4 and solvent removed under reduced pressure to afford crude material which was purified by column chromatography over silica gel to afford the title compound (0.065 g, 29% yield). LCMS: 515.40 (M+1)+; HPLC % 96.73 ( 254 nm) (Rt; 4.362; Method: Column: YMC ODS-A 150 mm4.6 mm5mu; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 muL, Col. Temp.: 30 C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% Bin 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) delta 11.45 (s, 1H), 8.16 (t, 1H), 7.64 (d, 2H, J=6.8 Hz), 7.45 (d, 2H), 7.30 (s, 1H), 7.16 (s, 1H), 5.85 (s, 1H), 4.28 (d, 2H, J=4.4 Hz), 2.75 (t, 1H), 2.65 (s, 3H), 2.32-2.42 (m, 6H), 2.20 (s, 6H), 2.10 (s, 3H), 1.69 (m, 4H), 1.53-1.56 (m, 1H), 1.42-1.45 (m, 2H), 1.10-1.23 (m, 4H).

Reference： [1]Patent: US2012/264734,2012,A1 .Location in patent: Page/Page column 112

13
[ 70799-12-1 ]
[ 1403257-80-6 ]
[ 1403255-32-2 ]

Yield	Reaction Conditions	Operation in experiment
53.8%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere;	Step 3: Synthesis of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4'-((dimethylamino)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1'-biphenyl]-3-carboxamide To a stirred solution of <strong>[1403257-80-6]5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzamide</strong> (0.2 g, 0.42 mmol) and (4-((dimethylamino)methyl)phenyl)boronic acid (0.15 g, 0.505 mmol) in dioxane/water mixture (5 mL+1 mL), Na2CO3 (0.16 g, 1.51 mmol) was added and the solution purged with argon for 15 min. Pd (PPh3)4 (0.048 g, 0.042 mmol) was the added and the reaction mixture again purged with argon for 10 min. The reaction mixture was heated at 100 C. for 2 h. The reaction mixture was then diluted with water and extracted with 10% MeOH/DCM. The combined extracts were dried over Na2SO4 and the solvent removed under reduced pressure to afford the crude product which was purified by column chromatography over silica gel to afford the title compound (0.120 g, 53.8%). LCMS: 531.30 (M+1)+; HPLC: 94.88% ( 254 nm) (Rt; 3.949; Method: Column: YMC ODS-A 150 mm4.6 mm5mu; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 muL, Col. Temp.: 30 C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) delta 11.45 (s, 1H), 8.19 (t, 1H, J=4.4 Hz), 7.61 (d, 2H, J=8 Hz), 7.39-7.41 (m, 3H), 7.23 (s, 1H), 5.86 (s, 1H), 4.28 (d, 2H, J=4.8 Hz), 3.62-3.84 (m, 4H), 3.22-3.38 (m, 2H), 3.02-3.06 (m, 3H), 2.30 (bs, 6H), 2.24 (s, 3H), 2.20 (s, 3H), 2.10 (s, 3H), 1.64-1.67 (m, 2H), 1.51-1.53 (m, 2H), 0.83 (t, 3H, J=6.8 Hz).

Reference： [1]Patent: US2012/264734,2012,A1 .Location in patent: Page/Page column 140

14
[ 70799-12-1 ]
[ 1542068-03-0 ]
[ 1542068-08-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1089 - 1103

15
[ 70799-12-1 ]
[ 1542068-03-0 ]
[ 1542068-05-2 ]

Yield	Reaction Conditions	Operation in experiment
57%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate; In 1,2-dimethoxyethane; water; at 100℃; for 3h;Inert atmosphere;	General procedure: To a degassed 3.5:1 mixture of dimethoxyethane and water (2mL), compound 5 (0.5mmol), the appropriate boronic acid (1mmol), PdCl2(dppf)CH2Cl2 (0.025mmol) and sodium bicarbonate (1.5mmol) were added under nitrogen. The mixture was heated for 1-4h. The layers were separated and the organic phase was evaporated. Purification by flash chromatography gave the desired compounds. Following this procedure compounds 1m-n, 6b-e, 6g-h, 6j, 6l-m, 11, 15 were prepared.
57%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate; In 1,2-dimethoxyethane; water; at 100℃; for 3h;Inert atmosphere;	A degassed dimethoxyethanelwater solution (3.5/1, 2.66 ml) containing 6-bromo-1H- pyrrolo[2,3-b]pyridine (131 mg, 0.66 mmol), phenyl-boronic acid (162 mg, 1.33 mmol), PdC12(dppf)DCM (24.3 mg, 0.033 mmol) and sodium bicarbonate (167 mg, 2mmol) was heated to 110C for 2 hours under a nitrogen atmosphere. The layers were then separated and the organic phase was concentrated under vacuum. The crude reaction mixture was purified by flash chromatography to give the desired 6- phenylpyrrolo[2,3-b]pyridine as a white solid.Purification: Hexane/AcOEt: 9/1.This step was completed at 100C in 3 h following the procedure described in step A of example 1 using <strong>[70799-12-1][4-(dimethylaminomethyl)phenyl]boronic acid</strong> instead of phenyl-boronic acid. Purification: DCM/MeOH: 95/5 to get the desired adduct as a white sticky solid.Yield: 57%.1H NMR (300 MHz CDC13), 5: 8.05-7.92 (3H, m); 7.67 (1H, d, J = 8.1 Hz); 7.61 (1H, d, J = 3.7 Hz); 7.56-7.47 (2H, m); 7.41 (1H, m); 6.92-6.79 (4H, m); 6.62 (1H, d, J = 3.7Hz); 4.61 (4H, s); 3.94 (2H, s); 3.81 (6H, s); 2.61 (6H, s).

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1089 - 1103
[2]Patent: WO2015/11008,2015,A1 .Location in patent: Page/Page column 11; 12; 23; 24

16
[ 70799-12-1 ]
C₁₁H₈BrN₅ [ No CAS ]
C₂₀H₂₀N₆ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 4546 - 4552

17
[ 70799-12-1 ]
5-(2-(benzylthio)-6-bromophenyl)-1H-tetrazole [ No CAS ]
[ 824-94-2 ]
4'-((dimethylamino)methyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-[1,1'-biphenyl]-3-sulfonamide [ No CAS ]
4'-((dimethylamino)methyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-[1,1'-biphenyl]-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A 40 mL reaction vial was charged with the mixture of 3-bromo-2-(l-(4- methoxybenzyl)(lH-tetrazol-5-yl))benzenesulfonamide and 3-bromo-2-(2-(4- methoxybenzyl)(lH-tetrazol-5-yl))benzenesulfonamide (35 mg, 0.082 mmol), (4- ((dimethylamino)methyl)phenyl)boronic acid (44.3 mg, 0.247 mmol), potassium phosphate (52.5 mg, 0.247 mmol), diacetoxypalladium (5.56 mg, 0.025 mmol) and SPhos-Pd-G2 (20.32 mg, 0.049 mmol). The vial was capped via a red sure-seal cap, and the reaction was degassed via vacuum/nitrogen flushes (line with needle from manifold). THF (4 mL) was added via syringe, and again, the reaction was degassed via vacuum/nitrogen flushes. The reaction stirred at room temp for 15 minutes, and was then heated at 90C via an oil bath for 18 hours. The excess catalyst was filtered off and the reaction was concentrated, and then purified by reverse phase HPLC column (acetonitrile/water/0.05% TFA system) and eluted with 5% to 100% MeCN in water. The solution was concentrated to afford product. LC-MS: calculated for C24H26 6O3S 478.6; observed m/e: 479.2 (M+H)+ (Rt 0.79 / 2 min).
		Step C: 5-(2-(Benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole (0291) To a solution of 5-(2-(benzylthio)-6-bromophenyl)-1H-tetrazole in a mixture of chloroform and water (6 mL and 8 mL, respectively) were added potassium carbonate (1.544 g, 11.17 mmol), tetrabutylammonium chloride (0.311 g, 1.12 mmol) followed by a solution of 1-(chloromethyl)-4-methoxybenzene (1.14 mL, 8.38 mmol) in 2 mL of CHCl3 at 15 C. The resulting mixture was slowly warm to rt, and heated at 50 C. for 3 hr. The reaction mixture was cooled to rt, and transferred to a sep. funnel. The organic layer was separated, dried over MgSO4, filtered and purified using 5 to 80% ethyl acetate in hexanes to provide a mixture of 5-(2-(benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole. Step D: 3-Bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide (0292) To a solution of the mixture of 5-(2-(benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole in DCM (40 mL) was added water (0.251 mL, 13.9 mmol) followed by acetic acid (0.796 ml, 13.91 mmol). The resulting mixture was cooled to 0 C., then a solution of sulfuryl chloride (1.131 mL, 13.91 mmol) in DCM (2 mL) was slowly added. The reaction mixture was slowly warmed to rt, and stirred for 4 hr, and then evaporated to dryness. To this residue was added THF (5 mL) and then a mixture of aqueous ammonium hydroxide and THF (20 mL each) at 0 C. The reaction mixture was slowly warmed to rt and stirred for 1.5 hr. The resulting solution was diluted with ethyl acetate (100 mL), washed with water (50 mL) and brine (50 mL). The organic layer was dried over MgSO4, filtered and purified by column chromatography on silica gel eluted with 10 to 90% ethyl acetate in hexanes to provide mixture of 3-bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide. Step A: 4?-((Dimethylamino)methyl)-2-(1-(and 2-)(4-methoxybenzyl)-2-(1H-tetrazol-5-yl)-[1,1?-biphenyl]-3-sulfonamide (0845) A 40 mL reaction vial was charged with the mixture of 3-bromo-2-(1-(4-methoxybenzyl)(1H-tetrazol-5-yl))benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)(1H-tetrazol-5-yl))benzenesulfonamide (35 mg, 0.082 mmol), <strong>[70799-12-1](4-((dimethylamino)methyl)phenyl)boronic acid</strong> (44.3 mg, 0.247 mmol), potassium phosphate (52.5 mg, 0.247 mmol), diacetoxypalladium (5.56 mg, 0.025 mmol) and SPhos-Pd-G2 (20.32 mg, 0.049 mmol). The vial was capped via a red sure-seal cap, and the reaction was degassed via vacuum/nitrogen flushes (line with needle from manifold). THF (4 mL) was added via syringe, and again, the reaction was degassed via vacuum/nitrogen flushes. The reaction stirred at room temp for 15 minutes, and was then heated at 90 C. via an oil bath for 18 hours. The excess catalyst was filtered off and the reaction was concentrated, and then purified by reverse phase HPLC column (acetonitrile/water/0.05% TFA system) and eluted with 5% to 100% MeCN in water. The solution was concentrated to afford product. LC-MS: calculated for C24H26N6O3S 478.6; observed m/e: 479.2 (M+H)+ (Rt 0.79/2 min).

Reference： [1]Patent: WO2015/112441,2015,A1 .Location in patent: Page/Page column 240
[2]Patent: US2016/333021,2016,A1 .Location in patent: Paragraph 0291; 0292; 0845

18
6-bromo-1-cyclohexyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one [ No CAS ]
[ 70799-12-1 ]
1-cyclohexyl-6-(4-((dimethylamino)methyl)phenyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one [ No CAS ]

Reference： [1]ChemMedChem,2015,vol. 10,p. 1809 - 1820

19
[ 70799-12-1 ]
5-(2-(benzylthio)-6-bromophenyl)-1H-tetrazole [ No CAS ]
[ 76-05-1 ]
4′-((dimethylamino)methyl)-2-(1H-tetrazol-5-yl)-[1,1′-biphenyl]-3-sulfonamide trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step C: 5-(2-(Benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole (0291) To a solution of 5-(2-(benzylthio)-6-bromophenyl)-1H-tetrazole in a mixture of chloroform and water (6 mL and 8 mL, respectively) were added potassium carbonate (1.544 g, 11.17 mmol), tetrabutylammonium chloride (0.311 g, 1.12 mmol) followed by a solution of 1-(chloromethyl)-4-methoxybenzene (1.14 mL, 8.38 mmol) in 2 mL of CHCl3 at 15 C. The resulting mixture was slowly warm to rt, and heated at 50 C. for 3 hr. The reaction mixture was cooled to rt, and transferred to a sep. funnel. The organic layer was separated, dried over MgSO4, filtered and purified using 5 to 80% ethyl acetate in hexanes to provide a mixture of 5-(2-(benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole. Step D: 3-Bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide (0292) To a solution of the mixture of 5-(2-(benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole in DCM (40 mL) was added water (0.251 mL, 13.9 mmol) followed by acetic acid (0.796 ml, 13.91 mmol). The resulting mixture was cooled to 0 C., then a solution of sulfuryl chloride (1.131 mL, 13.91 mmol) in DCM (2 mL) was slowly added. The reaction mixture was slowly warmed to rt, and stirred for 4 hr, and then evaporated to dryness. To this residue was added THF (5 mL) and then a mixture of aqueous ammonium hydroxide and THF (20 mL each) at 0 C. The reaction mixture was slowly warmed to rt and stirred for 1.5 hr. The resulting solution was diluted with ethyl acetate (100 mL), washed with water (50 mL) and brine (50 mL). The organic layer was dried over MgSO4, filtered and purified by column chromatography on silica gel eluted with 10 to 90% ethyl acetate in hexanes to provide mixture of 3-bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide. Step A: 4?-((Dimethylamino)methyl)-2-(1-(and 2-)(4-methoxybenzyl)-2-(1H-tetrazol-5-yl)-[1,1?-biphenyl]-3-sulfonamide (0845) A 40 mL reaction vial was charged with the mixture of 3-bromo-2-(1-(4-methoxybenzyl)(1H-tetrazol-5-yl))benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)(1H-tetrazol-5-yl))benzenesulfonamide (35 mg, 0.082 mmol), <strong>[70799-12-1](4-((dimethylamino)methyl)phenyl)boronic acid</strong> (44.3 mg, 0.247 mmol), potassium phosphate (52.5 mg, 0.247 mmol), diacetoxypalladium (5.56 mg, 0.025 mmol) and SPhos-Pd-G2 (20.32 mg, 0.049 mmol). The vial was capped via a red sure-seal cap, and the reaction was degassed via vacuum/nitrogen flushes (line with needle from manifold). THF (4 mL) was added via syringe, and again, the reaction was degassed via vacuum/nitrogen flushes. The reaction stirred at room temp for 15 minutes, and was then heated at 90 C. via an oil bath for 18 hours. The excess catalyst was filtered off and the reaction was concentrated, and then purified by reverse phase HPLC column (acetonitrile/water/0.05% TFA system) and eluted with 5% to 100% MeCN in water. The solution was concentrated to afford product. LC-MS: calculated for C24H26N6O3S 478.6; observed m/e: 479.2 (M+H)+ (Rt 0.79/2 min). Step B: 4?-((Dimethylamino)methyl)-2-(1H-tetrazol-5-yl)-[1,1?-biphenyl]-3-sulfonamide, TFA salt (0846) The residue was dissolved in TFA (500 muL) and anisole (7.23 mg, 0.067 mmol) and heated to 45 C. for 18 hr. The reaction mixture was purified by reverse phase HPLC column (acetonitrile/water/0.05% TFA system) and eluted with 0% to 20% MeCN in water. The solution was concentrated to afford 4?-((dimethylamino)methyl)-2-(1H-tetrazol-5-yl)-[1,1?-biphenyl]-3-sulfonamide, TFA salt. LC-MS: calculated for C16H18N6O2S 358.4; observed m/e: 359.3 (M+H)+; 1H NMR delta (ppm) (MeOH): 8.24 (d, 1H), 7.88 (t, 1H), 7.78 (d, 1H), 7.40 (d, 2H), 7.22 (d, 2H), 4.26 (s, 2H), 2.80 (s, 6H).

Reference： [1]Patent: US2016/333021,2016,A1 .Location in patent: Paragraph 0291; 0292; 0845; 0846

20
[ 70799-12-1 ]
[ 128676-85-7 ]
2-chloro-3-(4-((dimethylamino) methyl)phenyl)quinoline [ No CAS ]

Reference： [1]ChemMedChem,2017,vol. 12,p. 106 - 119

21
[ 916429-26-0 ]
[ 70799-12-1 ]
3-(4-N,N-dimethylaminomethyl)phenyl-2-chloro-6-bromoquinoline [ No CAS ]

Reference： [1]ChemMedChem,2017,vol. 12,p. 106 - 119

22
[ 70799-12-1 ]
6-bromo-3-iodo-2-(naphthalen-1-ylmethoxy)quinoline [ No CAS ]
6-bromo-3-(4-((dimethylamino)methyl)phenyl)-2-(naphthalen-1-ylmethoxy)quinoline [ No CAS ]

Reference： [1]ChemMedChem,2017,vol. 12,p. 106 - 119

23
[ 70799-12-1 ]
4-chloro-2,8-dimethyl-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl]quinoline-7-carboxamide [ No CAS ]
4-[4-[(dimethylamino)methyl]phenyl]-2,8-dimethyl-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl]quinoline-7-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%	With potassium phosphate; dicyclohexylphosphino-2?,6?-di-i-propoxy-1,1?-biphenyl; In water; N,N-dimethyl-formamide; at 75℃; for 2h;	4-Chloro-2,8-dimethyl-N-[(6-methyl-2-oxo-4-propyl-l,2-dihydropyridin-3-yl)mem^ carboxamide (example 21) (62 mg, 0.16 mmol) and <strong>[70799-12-1]{4-[(dimethylamino)methyl]phenyl}boronic acid</strong> (36.3 mg, 0.2 mmol) were solved in N,N-dimethylformamide (2 ml) and treated with RuPhos- Pd-G2 (24 mg, 0.03 mmol) and 0.5 M aqeous potassium phosphate solution (0.93 ml, 0.47 mmol). The reaction mixture was stirred at 75C for 120 min. Purification via HPLC (method 8) gave 16 mg (19% of theory) of the title compound. NMR (400 MHz, DMSO-d6) delta ppm 0.87 (t, 3 H) 1.51 - 1.63 (m, 2 H) 2.21 (s, 6 H) 2.25 (s, 3 H) 2.32 - 2.40 (m, 3 H) 2.69 - 2.76 (2s, 6 H) 3.48 - 3.51 (m, 2 H) 4.34 (d, 2 H) 5.90 (s, 1 H) 7.34 (d, 1 H) 7.39 (s, 1 H) 7.43 - 7.52 (m, 4 H) 7.63 (d, 1 H) 8.26 - 8.33 (m, 1 H) 11.43 - 11.51 (m, 1 H). UPLC (method 1) [M+H]+ 497.4, 0.84 min.

Reference： [1]Patent: WO2017/25493,2017,A1 .Location in patent: Page/Page column 92-93

24
[ 70799-12-1 ]
8-bromo-N-(furan-2-2-ylmethyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine [ No CAS ]
C₁₉H₂₀N₆O [ No CAS ]