[ CAS No. 405520-68-5 ] {[proInfo.proName]}

Name: 405520-68-5|(4-(Dimethylcarbamoyl)phenyl)boronic acid|97%
Brand: Ambeed
SKU: A179852
Price: 10.0 USD
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2D 3D

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Quality Control of [ 405520-68-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 405520-68-5 ]

SDS Specification

Alternatived Products of [ 405520-68-5 ]

Product Details of [ 405520-68-5 ]

CAS No. :	405520-68-5	MDL No. :	MFCD02258943
Formula :	C₉H₁₂BNO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QJYYVSIRDJVQJW-UHFFFAOYSA-N
M.W :	193.01	Pubchem ID :	3503767
Synonyms :

Calculated chemistry of [ 405520-68-5 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	54.17
TPSA :	60.77 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) :	-7.27 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.29
Log Po/w (WLOGP) :	-0.93
Log Po/w (MLOGP) :	0.11
Log Po/w (SILICOS-IT) :	-1.28
Consensus Log Po/w :	-0.36

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.34
Solubility :	8.85 mg/ml ; 0.0459 mol/l
Class :	Very soluble
Log S (Ali) :	-1.13
Solubility :	14.4 mg/ml ; 0.0744 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.35
Solubility :	8.6 mg/ml ; 0.0446 mol/l
Class :	Soluble

Medicinal Chemistry

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

Safety of [ 405520-68-5 ]

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 [ 405520-68-5 ]

* 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 [ 405520-68-5 ]
Downstream synthetic route of [ 405520-68-5 ]

[ 405520-68-5 ] Synthesis Path-Upstream 1~3

1
[ 124-40-3 ]
[ 332154-57-1 ]
[ 405520-68-5 ]

Reference： [1] Patent: WO2004/22529, 2004, A2, . Location in patent: Page 35

2
[ 5720-05-8 ]
[ 405520-68-5 ]

Reference： [1] Patent: WO2004/22529, 2004, A2,

3
[ 76-09-5 ]
[ 405520-68-5 ]
[ 400727-57-3 ]

Reference： [1] Journal of the American Chemical Society, 2013, vol. 135, # 7, p. 2552 - 2559
[2] Organic Letters, 2015, vol. 17, # 12, p. 3086 - 3089

[ 405520-68-5 ] Synthesis Path-Downstream 1~88

1
[ 854948-92-8 ]
[ 405520-68-5 ]
acetic acid 2-[4-(4-dimethylcarbamoyl-phenyl)-8-(morpholine-4-sulfonyl)-1,3-dioxo-1,3-dihydro-pyrrolo[3,4-<i>c</i>]quinolin-2-yl]-ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 3680 - 3683

2
[ 945244-17-7 ]
[ 405520-68-5 ]
[ 945240-23-3 ]

Yield	Reaction Conditions	Operation in experiment
34%	With potassium carbonate;Pd-FibreCat 1007; In N,N-dimethyl-formamide; at 80℃; for 3h;	Step b: 5'-(1-(Benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(hydroxymethyl)-N,N-dimethylbiphenyl-4-carboxamide 1-(Benzo[d][1,3]dioxol-5-yl)-N-(3-bromo-4-(hydroxymethyl)-phenyl)cyclopropanecarboxamide (39 mg, 0.10 mmol), 4-(dimethylcarbamoyl)-phenylboronic acid (29 mg, 0.15 mmol), 1 M K2CO3 (0.3 mL, 0.3 mmol), Pd-FibreCat 1007 (8 mg, 0.1 mmol), and N,N-dimethylformamide (1 mL) were combined. The mixture was heated at 80 C. for 3 h. After cooling, the mixture was filtered and purified by reverse phase HPLC to yield 5'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(hydroxymethyl)-N,N-dimethylbiphenyl-4-carboxamide (16 mg, 34%). ESI-MS m/z calc. 458.5, found 459.5 (M+1)+; Retention time 2.71 minutes.
34%	With K2CO3; In N,N-dimethyl-formamide;	Step b: 5'-(1-(Benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(hydroxymethyl)-N,N-dimethylbiphenyl-4-carboxamide 1-(Benzo[d][1,3]dioxol-5-yl)-N-(3-bromo-4-(hydroxymethyl)-phenyl)cyclopropanecarboxamide (39 mg, 0.10 mmol), 4-(dimethylcarbamoyl)-phenylboronic acid (29 mg, 0.15 mmol), 1 M K2CO3 (0.3 mL, 0.3 mmol), Pd-FibreCat 1007 (8 mg, 0.1 mmol), and N,N-dimethylformamide (1 mL) were combined. The mixture was heated at 80 C. for 3 h. After cooling, the mixture was filtered and purified by reverse phase HPLC to yield 5'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(hydroxymethyl)-N,N-dimethylbiphenyl-4-carboxamide (16 mg, 34%). ESI-MS m/z calc. 458.5, found 459.5 (M+1)+; Retention time 2.71 minutes.
34%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 3h;	1-(Benzo[d][1,3]dioxol-5-yl)-N-(3-bromo-4-(hydroxymethyl)-phenyl)cyclopropanecarboxamide (39 mg, 0.10 mmol), 4-(dimethylcarbamoyl)-phenylboronic acid (29 mg, 0.15 mmol), 1 M K2CO3 (0.3 mL, 0.3 mmol), Pd-Fibre Cat 1007 (8 mg, 0.1 mmol), and N,N-dimethylformamide (1 mL) were combined. The mixture was heated at 80 C. for 3 h. After cooling, the mixture was filtered and purified by reverse phase HPLC to yield 5'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(hydroxymethyl)-N,N-dimethylbiphenyl-4-carboxamide (16 mg, 34%). ESI-MS m/z calc. 458.5. found 459.5 (M+1)+; Retention time 2.71 minutes.

Reference： [1]Patent: US2008/9524,2008,A1 .Location in patent: Page/Page column 390; 391
[2]Patent: US2011/98311,2011,A1
[3]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 1164

3
[ 945244-18-8 ]
[ 405520-68-5 ]
[ 945240-99-3 ]

Yield	Reaction Conditions	Operation in experiment
20%	With potassium carbonate;Pd-FibreCat 1007; In N,N-dimethyl-formamide; at 150℃; for 0.166667h;Microwave irradiation;	Step b: 5'-(1-(Benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(cyanomethyl)-N,N-dimethylbiphenyl-4-carboxamide 1-(Benzo[d][1,3]dioxol-5-yl)-N-(3-bromo-4-(cyanomethyl)phenyl)cyclopropane-carboxamide (40 mg, 0.10 mmol), 4-(dimethylcarbamoyl)phenylboronic acid (29 mg, 0.15 mmol), 1 M K2CO3 (0.2 mL, 0.2 mmol), Pd-FibreCat 1007 (8 mg, 0.1 mmol), and N,N-dimethylformamide (1 mL) were combined. The mixture was irradiated in the microwave at 150 C. for 10 minutes. Volatiles were removed in vacuo and crude product was purified by chromatography on silica gel (eluding with 0-100% ethyl acetate in hexanes) to afford 5'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(cyanomethyl)-N,N-dimethylbiphenyl-4-carboxamide (9.1 mg, 20%). ESI-MS m/z calc. 467.2, found 468.5 (M+1)+; retention time 2.96 minutes.
20%	With K2CO3; In N,N-dimethyl-formamide;	Step b: 5'-(1-(Benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(cyanomethyl)-N,N-dimethylbiphenyl-4-carboxamide 1-(Benzo[d][1,3]dioxol-5-yl)-N-(3-bromo-4-(cyanomethyl)phenyl)cyclopropane-carboxamide (40 mg, 0.10 mmol), 4-(dimethylcarbamoyl)phenylboronic acid (29 mg, 0.15 mmol), 1 M K2CO3 (0.2 mL, 0.2 mmol), Pd-FibreCat 1007 (8 mg, 0.1 mmol), and N,N-dimethylformamide (1 mL) were combined. The mixture was irradiated in the microwave at 150 C. for 10 minutes. Volatiles were removed in vacuo and crude product was purified by chromatography on silica gel (eluting with 0-100% ethyl acetate in hexanes) to afford 5'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(cyanomethyl)-N,N-dimethylbiphenyl-4-carboxamide (9.1 mg, 20%). ESI-MS m/z calc. 467.2, found 468.5 (M+1)+; retention time 2.96 minutes.
20%	With potassium carbonate; In N,N-dimethyl-formamide; at 150℃; for 0.166667h;Microwave irradiation;	1-(benzo[d][1,3]dioxol-5-yl)-N-(3-bromo-4-(cyanomethyl)phenyl)cyclopropane-carboxamide (40 mg, 0.10 mmol), 4-(dimethylcarbamoyl)phenylboronic acid (29 mg, 0.15 mmol), 1 M K2CO3 (0.2 mL, 0.2 mmol), Pd-FibreCat 1007 (8 mg, 0.1 mmol), and N,N-dimethylformamide (1 mL) were combined. The mixture was irradiated in the microwave at 150 C. for 10 minutes. Volatiles were removed in vacuo and crude product was purified by chromatography on silica gel (eluting with 0-100% ethyl acetate in hexanes) to afford 5'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(cyanomethyl)-N,N-dimethylbiphenyl-4-carboxamide (9.1 mg, 20%). ESI-MS m/z calc. 467.2. found 468.5 (M+1)+; retention time 2.96 minutes.

Reference： [1]Patent: US2008/9524,2008,A1 .Location in patent: Page/Page column 392
[2]Patent: US2011/98311,2011,A1
[3]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 1171

4
[ 648904-46-5 ]
[ 405520-68-5 ]
[ 862081-57-0 ]

Yield	Reaction Conditions	Operation in experiment
	With cesium fluoride; tricyclohexylphosphine;palladium diacetate; In acetonitrile; at 90℃; for 1.5h;	Combine trifluoromethanesulfonic acid 6-methoxy-1- [4- (2-piperidin-1-yl-ethoxy)- phenoxy]-naphthalen-2-yl ester (247 mg, 0.47 mmol), 4- (N, N- Dimethylaminocarbonyl) phenylboronic acid (272 mg, 1.41 mmol), palladium acetate (II), (32 mg, 0.14 mmol), cesium fluoride (643 mg, 4.23 mmol), tricyclohexylphosphine (43mg, 0.16 mmol) and acetonitrile (7 mL), stir and heat at 90C. After 90 min, cool to ambient temperature and filter through celite. Purify the crude reaction mixture using radial chromatography eluting with 4% methanol in dichloromethane, combining product fractions to give 256 mg of4- {6-methoxy-l- [4- (2-piperidin-l-yl-ethoxy)-phenoxy]- naphthalen-2-yl}-N, N-dimethyl-benzamide. Form the hydrochloride salt by adding 0.8 mL of a IN HCl in Et20 solution and dry to give 264 mg of the corresponding hydrochloride salt. Prepare the title compound in a manner analogous to that of 5- {6-hydroxy-1- [4- (2- piperidin-l-yl-ethoxy)-phenoxy]-naphthalen-2-yl}-2, 3-dihydro-isoindol-l-one hydrochloride using 4- {6-methoxy-1- [4- (2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen- 2-yl}-N, N-dimethyl-benzamide hydrochloride (264mg, 0.47mmol). Purify the crude product by radial chromatography to yield 122 mg (51%) of the free base of title compound. Mass spectrum (ion spray): m/z =511 (M+1). Form the hydrochloride salt by adding 0.7 mL of a IN HCl in Et20 solution to give 131 mg of the title compound.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3544 - 3549
[2]Patent: WO2005/73205,2005,A1 .Location in patent: Page/Page column 38-39

5
[ 124-40-3 ]
[ 332154-57-1 ]
[ 405520-68-5 ]

Yield	Reaction Conditions	Operation in experiment
		4-(Dihydroxyboryl) benzoic acid (34.4 g, 0.21 mol) was added to thionyl chloride (300 ml), the reaction mixture was heated at reflux overnight and evaporated to dryness, the residue was added dimethylamine (167 ml of a 40% solution in water), the reaction mixture was heated at reflux for 20 min. and filtered while still hot, the filtrate was cooled to room temperature and added concentrated hydrochloric acid and the title compound precipitated. Yield 25.1 g.

Reference： [1]Patent: WO2004/22529,2004,A2 .Location in patent: Page 35

6
[ 39263-32-6 ]
[ 405520-68-5 ]
[ 674299-31-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; for 0.666667h;Heating / reflux;	4-(Dihydroxyboryl)-(N,N-dimethylbenzamide) (1.2 g, 6.2 mmol), 2-amino-5-bromobenzonitrile (1.1 g, 5.6 mmol, 0.9 eq), potassium carbonate (2.3g, 16.9 mmol, 3.3 eq.), dimethoxyethylenglycol (20 ml) and water (10 ml) was mixed nitrogen was bobbled through the mixture, bis(triphenylphosphine)palladium (II) chloride (0.05 g) was added, the reaction mixture was heated at reflux for 40 min, cooled to room temperature, added water (50 ml) and extracted with ethyl acetate (50 ml), the organic phase was washed with water (30 ml) dried, evaporated and the title compound was left as an oil. Yield 1.17 g.

Reference： [1]Patent: WO2004/22529,2004,A2 .Location in patent: Page 35

7
[ 3141-27-3 ]
[ 405520-68-5 ]
[ 857334-83-9 ]

Yield	Reaction Conditions	Operation in experiment
59%	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃;	4-(N, N-Dimethylaminocarbonyl) phenylboronic acid (415 mg, 2.15 mmole), 2-5- dibromothiophene (1.14 grams, 4.73 mmole), cesium carbonate (2.1 grams, 6.45 mmole), and tetrakis (triphenylphosphine) palladium (240 mg, 0.22 mmole) were slurried in ethylene glycol dimethyl ether/water/ethanol (7: 3: 2,20 ml). The mixture was heated in a round bottom flask at 80 C overnight. The mixture was cooled, treated with water and extracted with chloroform (3 times). The organic layers were combined, dried over sodium sulfate, filtered, and evaporated under reduced pressure to afford the product as an oil. The oil was purified on silica gel using 40% ethyl acetate in hexanes as the eluant. The compound was obtained as a pale yellow solid (59% recovery).'HNMR (300. 132 MHz, DMSO) 6 7. 67 (d, J= 9. 4 Hz, 1H), 7.46-7. 43 (m, 3H), 7.29 (d, J= 4. 7 Hz, 1H), 2.95 (s, 6H); MS m/z : 311 (M+H) +.
59%	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃;	4-(iV,N-Dimethylaminocarbonyl)phenylboronic acid (415 mg, 2.15 mmole), 2-5- dibromothiophene (1.14 grams, 4.73 mmole), cesium carbonate (2.1 grams, 6.45 mmole), and tetrakis(triphenylphosphine)palladium (240 mg, 0.22 mmole) were slurried in ethylene glycol dimethyl ether/water/ethanol (7:3:2, 20 mL). The mixture was heated in a round bottom flask at 80 0C overnight. The mixture was cooled, treated with water and extracted with chloroform (3 times). The organic layers were combined, dried over sodium sulfate, filtered, and evaporated under reduced pressure to afford the product as an oil. The material was purified on silica gel using 40% ethyl acetate in hexanes as the eluant. The compound was obtained as a pale yellow solid (59% recovery). 1H NMR (300.132 MHz, DMSO) delta 7.67 (d, EPO <DP n="15"/>J= 9.4 Hz, IH), 7.46 - 7.43 (m, 3H), 7.29 (d, J= 4.7 Hz, IH), 2.95 (s, 6H); MS m/z: 311(M+H)+.

Reference： [1]Patent: WO2005/61510,2005,A1 .Location in patent: Page/Page column 21-22
[2]Patent: WO2006/65209,2006,A1 .Location in patent: Page/Page column 13; 14

8
[ 760987-24-4 ]
[ 405520-68-5 ]
methyl [3-(2-[((1E)-1-{4'-[(dimethylamino)carbonyl]biphenyl-4-yl}propylidene)amino]oxy}ethoxy)phenyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 90℃; for 1h;	A solution of methyl {3-[2-([(1E)-1-(4-bromophenyl)propylidene]amino}oxy)ethoxy]phenyl}acetate (635mg) in dimethoxyethane (6.0mL) was added by p-dimethylaminocarbonylbenzeneboronic acid (353mg), sodium carbonate (205mg) aqueous solution and tetrakis(triphenylphosphine)palladium(0) (89mg) successively and the mixture was stirred for an hour at 90C. The mixture was cooled down till room temperature, added by water and filtrated. The filtrate was extracted by ethyl acetate and the organic layer was washed with water and saturated brine successively, dried over and then concentrated. The residue was purified by column to give the title compounds having the following physical data. TLC:Rf 0.16 (n-hexane : ethyl acetate = 1 : 1).

Reference： [1]Patent: EP1602642,2005,A1 .Location in patent: Page/Page column 59-60

9
[ 874347-40-7 ]
[ 405520-68-5 ]
C₃₃H₄₅N₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate; caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 60℃; for 5.5h;	In a flask were combined 82 (100 mg), 4-(dimethylaminocarbonyl)phenylboronic acid (71 mg), Cs2CO3 (120 mg), KOAc (20 mg), and Pd(dppf)Cl2 (10 mg). The flask was flushed with Ar, and DMSO (6 mL) added; the material was then heated at 60 C. during 3 h, with the more Pd(dppf)Cl2 (5 mg) added after 2.5 h. The reaction mixture was cooled and added to DCM (25 mL) and 1% NaS2CNMe2 (75 mg); the laters were separated and the aqueous phase extracted 3×25 mL DCM. The combined organics were washed with water (25 mL) and brine (25 mL), then dried on Na2SO4. Concentration and HPLC putification of the material gave 118 as a white solid, 64. mg. MS (ESI(+)) m/e 564.3 (M+H)+.

Reference： [1]Patent: US2006/25460,2006,A1 .Location in patent: Page/Page column 116

10
[ 874347-47-4 ]
[ 405520-68-5 ]
C₃₄H₄₇N₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; In ethanol; at 120℃; for 0.333333h;Microwave;	Compound 144 (30 mg), along with 4-(dimethylaminocarbonyl)phenylboronic acid (21 mg), Pd(Ph3P)2Cl2 (2 mg), and NEt3 (31 muL), was dissolved in EtOH (900 muL), which was heated in the microwave at 120 C. during 20 minutes. The reaction mixture was added to silica gel (1 g) and the solvent allowed to evaporate; purification of the residue by silica gel chromatography gave a single diastereomer of 138 as a white solid, 30 mg. MS (ESI(+)) m/e 578.3 (M+H)+.

Reference： [1]Patent: US2006/25460,2006,A1 .Location in patent: Page/Page column 126

11
[ 874347-54-3 ]
[ 405520-68-5 ]
[ 874347-55-4 ]

Yield	Reaction Conditions	Operation in experiment
53%	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; In ethanol; at 120℃; for 0.333333h;Microwave;	To a solution of aryl bromide 168 (500 mg, 2 mmol) in EtOH (5 mL) was added Et3N (651 muL, 5 mmol), [4-(N,N-dimethylaminocarbony)phenyl]boronic acid (391 mg, 2 mmol) and Pd(PPh3)3Cl2 (109 mg, 0.2 mmol). The mixture was heated by microwave at 120 C. for 20 min and then concentrated and purified by flash chromatography to yield 320 mg (53%) of 169.

Reference： [1]Patent: US2006/25460,2006,A1 .Location in patent: Page/Page column 134-135

12
[ 914606-86-3 ]
[ 405520-68-5 ]
4-(6-(4-cyclopropylpiperazin-1-yl)-piperidin-3-yl)-N,N-dimethylbenzamide dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 80℃; for 1.5h;	Step 3: A mixture of 1-(5-bromopyridin-2-yl)-4-cyclopropylpiperazine, (2.5 g, 8.86 mmol), 4-(N, N- dimethylaminocarbonyl)-phenyl boronic acid (2.5 g, 13.0 mmol), tetrakis(triphenylphosphine)- palladium(O) (300 mg, 0.26 mmol), and anhydrous sodium carbonate (2.0 g, 18.9 mmol) was purged with nitrogen. 1 ,2-Dimethoxyethane (30 ml_) and water (7 ml_) were added and the reaction mixture was heated at 800C for 1 .5 hours and filtered upon cooling to 0-50C. The crystals were washed with water (20 ml_), dried and then dissolved in acetone (130 ml_). Addition of HCI9 in methanol afforded 1 .41 g (37 %) of 4-[6-(4-cyclopropylpiperazin-1 -yl)- piperidin-3-yl]-N,N-dimethylbenzamide, dihydrochloride.1H NMR (400 MHz, DMSO-c(6) delta 1 1 .36 (brs, 1 H), 8.50 (d, 1 H), 8.18 (dd, 1 H) 7.75 (d, 2H), 7.50 (d, 2H), 7.26 (d, 1 H), 4.51 (d, 2H), 3.56 (m, 4H), 3.53 (brs, 2H), 3.00 (s, 3H), 2.96 (s, 3H), 2.89 (brs, 1 H), 1 .20 (m, 2H), 0.82 (m, 2H).

Reference： [1]Patent: WO2007/3604,2007,A2 .Location in patent: Page/Page column 103-104

13
[ 928656-45-5 ]
[ 405520-68-5 ]
6'-amino-N4,N4-dimethyl-1,1':3',1"-terphenyl-4,5'-dicarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 150℃; for 0.333333h;Microwave irradiation;	Example 59 : 6'-Amino-Lambda/4,Lambda/4-dimethyl-1,1l:3l,1"-terphenyl-4,5'-dicarboxamide; 4-Amino-5-bromo-3-biphenyl-carboxamide (Intermediate 7, 50 mg, 0.17 mmol), {4- [(dimethylamino)carbonyl]phenyl}boronic acid (50 mg, 0.26 mmol), sodium carbonate (109 mg, 1.03 mmol) and dichloro(1 ,r-bis-(diphenylphosphino)-ferrocene)palladium(ll)- EPO <DP n="97"/>dichloromethane adduct (13 mg, 0.017 mmol) were slurried with 1 ,4-dioxane (1 mL) and water (1 mL). The mixture was heated with stirring in a microwave reactor at 150 0C for 20 mins. The cooled mixture was filtered through a silica cartridge, eluting with methanol and the eluent concentrated in vacuo. The crude solid was dissolved in DMSO / methanol solution (1 :1 , 1 mL), filtered, and purified by preparative HPLC using a 20-60% MeCN (aq) gradient. Fractions corresponding to the desired product were identified by LCMS, and passed through an aminopropyl functionalised silica cartridge (pre-equilibrated with methanol, 2 column volumes), eluting with methanol. Concentration yielded the title compound (22.4 mg, 0.06 mmol).MS [M+1]+ 360.34; 1H NMR 4H (400.13 MHz, Cf6-DMSO, TMS): 8.10 (br s, 1 H), 7.91 d, J = 2.0 Hz, 1 H), 7.70 (d, J = 7.3HZ, 2H), 7.54 (d, J = 8.3Hz, 2H), 7.51 (d, J = 8.3Hz, 2H), 7.43-7.37 (m, 3H), 7.31 (br s, 1 H), 7.26 (t, J = 7.4Hz, 1 H), 6.39 (s, 2H), 3.00 (s, 6H).

Reference： [1]Patent: WO2007/25575,2007,A1 .Location in patent: Page/Page column 94-95

14
[ 1025959-29-8 ]
[ 405520-68-5 ]
6'-amino-4''-fluoro-N4,N4-dimethyl-1,1':3',1"-terphenyl-4,5'-dicarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 150℃; for 0.333333h;Microwave irradiation;	Example 63 6'-Amino-4"-fluoro-/V/V-dimethyM ,1 "tf1,. "-terphenyl-4,51- dicarboxamide; 4-Amino-5-bromo-41-fluoro-3-biphenyl-carboxamide (Intermediate 13, 53 mg, 0.17 mmol), {4-[(dimethylamino)carbonyl]phenyl}boronic acid (50 mg, 0.26 mmol), sodium carbonate (109 mg, 1.03 mmol) and dichloro(1 ,1'-bis-(diphenylphosphino)-ferrocene)palladium(ll)- dichloromethane adduct (13 mg, 0.017 mmol) were slurried with 1 ,4-dioxane (1 mL) and water (1 mL). The mixture was heated with stirring in a microwave reactor at 150 0C for 20 mins. The cooled mixture was diluted with methanol (10 mL), filtered through a silica cartridge (500 mg silica) and the eluent concentrated in vacuo. The resulting crude solid was dissolved in 1 :1 DMSO / methanol solution (1 mL), filtered, and purified by preparative HPLC using a 30-80% MeCN (aq) gradient. Fractions corresponding to the desired product were identified by LCMS, and passed through an aminopropyl functionalised silica cartridge (1 g sorbent, pre-equilibrated with methanol, 2 column volumes), eluting with methanol. Concentration in vacuo yielded the title compound (14.5 mg, 0.04 mmol) as a white solid.MS [M+1]+ 378.24, 1H NMR delta (400.13 MHz, Gf6-DMSO1 TMS): 8.10 (br s, 1 H), 7.88 (d, J = 1.8 Hz, 1 H), 7.74 (dd, J = 8.8, 5.5 Hz, 2H), 7.53 (d, J = 8.3Hz, 2H), 7.50 (d, J = 8.3Hz, 2H), 7.40 (d, J = 2.0 Hz, 1H), 7.32 (br s, 1 H), 7.23 (t, J = 8.9 Hz, 2H), 6.40 (br s, 2H), 3.00 (s, 6H).

Reference： [1]Patent: WO2007/25575,2007,A1 .Location in patent: Page/Page column 98

15
C₂₄H₃₅IN₂O₃ [ No CAS ]
[ 405520-68-5 ]
C₃₃H₄₅N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate; caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 60℃; for 5.5h;	EXAMPLE 9; Under an argon atmosphere compound 25 (synthesized according to procedure described in Example 1, compound 12) (100 mg), 4-(dimethylaminocarbonyl)phenylboronic acid (71 mg), Cs2CO3 (120 mg), KOAc (20 mg), and Pd(dppf)Cl2 (10 mg) were suspended in DMSO (6 mL) and heated at 60 C. during 3 h. Additional Pd(dppf)Cl2 (5 mg) was added to the reaction mixture after 2.5 h. The reaction mixture was then cooled to rt and diluted with DCM (25 mL) and then extracted with aqueous solution of NaS2CNMe2 (8 mL). The aqueous layer was separated and extracted with DCM (3×25 mL). The combined organics were washed with water (25 mL) and brine (25 mL), dried on Na2SO4, and concentrated under reduced pressure. The crude material was purified using silica gel column chromatography to yield the desired product.

Reference： [1]Patent: US2007/155705,2007,A1 .Location in patent: Page/Page column 29-30

16
[ 1039744-20-1 ]
[ 405520-68-5 ]
[ 1039743-71-9 ]

Yield	Reaction Conditions	Operation in experiment
	With oxygen; triethylamine;copper diacetate; In dichloromethane; at 20℃; for 18h;Molecular sieve;	General Procedure 19.8 (Copper mediated N-arylation); Example 19.8 Preparation of 4-{ r-[3-(dimethylamino)-l,2,4-thiadiazol-5-yl]-4,4'-bipiperidin-l-yl}-N,N- dimethylbenzamide; A suspension of 4-(dimethylaminocarbonyl)phenylboronic acid (276mg; 1.43 lmmol) in dichloromethane (1OmL) was treated with activated powdered 4A molecular sieves (1.5g), Cu(OAc)2 (87mg; 0.477mmol), compound 19.3 (141mg; 0.477mmol) and triethylamine (134I¼L; 0.954mmol). The reaction vessel was purged with oxygen and the mixture stirred under an oxygen atmosphere at ambient temperature for 18hr. The now brown mixture was filtered through Celite. The eluant was adsorbed onto silica gel. The silica gel was exhaustively eluted without fractionation (40: 1 CH2Cl2ZMeOH). The eluant was evaporated to a yellow oil and chromatographed (PTLC; 40: 1 CH2Cl2/MeOH). The major band was collected affording the title compound. LRMS calc: 442.3 obs: 443.2 (M+H).

Reference： [1]Patent: WO2008/85316,2008,A1 .Location in patent: Page/Page column 110

17
[ 53815-56-8 ]
[ 405520-68-5 ]
[ 1093119-18-6 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 105℃; for 0.416667h;	Compound 16-1 (251 mg, 1 mmol), <strong>[405520-68-5]4-(N,N-dimethylaminocarbonyl)phenylboronic acid</strong> (222 mg, 1.2 mmol) and anhydrous sodium carbonate (424 mg, 4 mmol) were dissolved in a mixture of 20 mL of DMF and 12 mL of water. Tetrakis(triphenylphosphine)palladium (56 mg, 0.05 mmol) was added, and the reaction was heated at 1050C under argon, for 25 min. 50 mL satd. sodium chloride solution and 900 muL of acetic acid were added, and the mixture was extracted with chloroform. The organic layer was evaporated, and the crude product was purified with column chromatography to afford 17-1 (186 mg, 0.58 mmol, 58%).

Reference： [1]Patent: WO2008/154484,2008,A1 .Location in patent: Page/Page column 124

18
[ 845889-22-7 ]
[ 405520-68-5 ]
C₂₅H₃₃N₅O₅S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4242 - 4248

19
[ 1093871-53-4 ]
[ 405520-68-5 ]
[ 1093871-36-3 ]

Yield	Reaction Conditions	Operation in experiment
58%	With potassium phosphate;palladium diacetate; CyJohnPhos; In water; toluene; at 85℃; for 16h;	3'-f5-Acetamido-l-methyl-lH-pyrazolo[3.,4-blpyri(iine-3-yl)-N,N-diimethylbiphenyl-4- carboxamide (B.I): Palladium acetate (3 mg, 0.013 mmol, 0.05 equ.) is added to a suspension of 7 (110 mg, 0.27 mmol), 4-(dimethylcarbamoyl)phenylboronic acid (82 mg, 0.43 mmol, 1.6 eq.), potassium phosphate (115 mg, 0.54 mmol, 2eq.), (2-biphenyl)dicyclohexyl phosphine (9.3 mg, 0.027 mmol, 0.1 eq.) in a degassed mixture of toluene: water (4.44 mL, 5:1). The reaction mixture is stirred under an atmosphere of nitrogen at 85 0C for 16 h. The layer of toluene is removed and the aqueous layer is washed with toluene (3 mL). The aqueous layer is extracted with dichloromethane (3x5 mL), the organic layers are combined and washed through a pad OfMgSO4 and silica eluting with hot diethyl ether, dichloromethane, ethyl acetate and finally 10 % methanol in ethyl acetate to afford 64 mg (58 %) of the title compound B.I. C24H23N5O2 (413.4): MS-APCI: 414.0 ([M+H]+). HPLC (system A) R1 in min (purity) = 3.80 (98).

Reference： [1]Patent: WO2009/832,2008,A2 .Location in patent: Page/Page column 21

20
[ 251996-52-8 ]
[ 405520-68-5 ]
C₂₄H₂₀N₂O₄S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4952 - 4955

21
[ 1149733-95-8 ]
[ 405520-68-5 ]
C₂₇H₂₂FN₅O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1807 - 1810

22
[ 1163303-27-2 ]
[ 405520-68-5 ]
C₄₂H₃₅N₅O₅S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 3136 - 3140

23
[ 945103-84-4 ]
[ 76-05-1 ]
[ 405520-68-5 ]
4-{4-[3-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-5,5-dimethyl-2,4-dioxo-imidazolidin-1-ylmethyl]-pyridin-2-yl}-N,N-dimethyl-benzamide trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		0,3.9 mmol of the product, of step 4 and 0,43;mmol of the.. corresponding acid, are dissolved in 5 ml of DMF, 0,.09rnmol-of Pd(PPh3)4 and 0,9 ml of 'IN Na2C03 are added and .the .resulting 'mixture is heated to 100 C until completion,. of...the ' reaction . (monitored ? by TLC)The '? '-solvent -is evaporated ". and 'the residue subjected to.-"chromatography"' ' ;on- ??'?-. ..?a-.":. .'. . . HPLC - .system.":V ' are"-' between-' . .20%'" and : ? , 70% Example 49 ? > ?4-{4-[3-(l-Acetyl-3,3-dimethyl-2,3-dihydro-lE-indol-6-yl) -5,-5-dimethyl-2, 4-dioxo- imidazolidin-1-ylmethyl]-pyridin-2-yl}-N,N~dimethyl-benzamide; compound withtrifluoro-acetic acid ??'-.-.Starting from . 1-(6-Amino-3,3-dimethyl-2,3-dihydro-indol-1-yl)-ethanone in step A and using steps, B, C, D and F,with 4-(N,N-DIMETHYLAMINOCARBONYL)PHENYLBORONIC ACIDM+H+ measured = 554.27 . .LC/MS retention time [min] =1.3

Reference： [1]Patent: WO2006/10642,2006,A1 .Location in patent: Page/Page column 80-81; 87

24
[ 1200575-54-7 ]
[ 405520-68-5 ]
[ 1200575-57-0 ]

Yield	Reaction Conditions	Operation in experiment
46%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 15h;	INTERMEDIATE A37V^V-Dimethyl-4-(2-piperidin-4-yl-4H-l,3-benzodioxin-6-yl)benzamide A suspension of 4-(6-bromo-4H-l,3-benzodioxin-2-yl)piperidine (Intermediate A2; 370 mg, 1.24 mmol), {4-[(dimethylamino)carbonyl]phenyl}boronic acid (264 mg, 1.36 mmol), Pd(PPh3)4 (72 mg, 0.0620 mmol) and K2CO3 (428 mg, 3.10 mmol) in 1,4-dioxane (10 mL) and water (3 mL) was heated at 90 0C for 15 h. The solvents were removed under reduced pressure. The residue was purified by flash chromatography on silica using EtOAc/DCM <n="64"/>- -(1:1) followed by DCM/MeOH/25% aqueous NH3 (90:9:1) as eluents. Yield 209 mg (46%). Analytical HPLC: purity 85% (System A); LRESIMS (ESI+) m/z = 367 (M+H)+.

Reference： [1]Patent: WO2009/150144,2009,A1 .Location in patent: Page/Page column 62-63

25
[ 1200575-51-4 ]
[ 405520-68-5 ]
[ 1200571-58-9 ]

Yield	Reaction Conditions	Operation in experiment
53%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃;	General Method Al: Suzuki-type cross-coupling reactionA suspension of benzyl 4-(6-bromo-4H-l,3-benzodioxin-2-yl)piperidine-l-carboxylate (Intermediate Al; 20 mg, 0.046 mmol), the appropriate boronic acid (0.051 mmol), K2CO3 (16 mg, 0.12 mmol) and Pd(PPh3)4 (3 mg, 0.0023 mmol) in 1,4-dioxane (2 mL) and water (0.5 mL) was heated at 90 0C overnight. The solvents were removed under reduced pressure and the residue was purified by preparative HPLC (System E).EXAMPLE AlBenzyl 4-(6- {4- [(dimethylamino)carbonyl] phenyl}-4H- 1 ,3-benzodioxin-2-yl)- piperidine-1-carboxylate The title compound was prepared from benzyl 4-(6-bromo-4H-l,3-benzodioxin-2-yl)- piperidine-1-carboxylate (Intermediate Al) and {4-[(dimethylamino)carbonyl]phenyl}- boronic acid using the conditions described in general method Al. Yield 12.2 mg (53%). Analytical etaPLC: purity 94% (System A and B); etaRESIMS (ESI+) calcd for C30H32N2O5 500.2311, found 500.2315.

Reference： [1]Patent: WO2009/150144,2009,A1 .Location in patent: Page/Page column 60; 73

26
[ 870521-18-9 ]
[ 405520-68-5 ]
C₃₀H₂₇F₃N₂O₆S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 77 - 105

27
[ 1198277-84-7 ]
[ 405520-68-5 ]
[ 1198277-94-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 2321 - 2325

28
[ 1225060-88-7 ]
[ 405520-68-5 ]
[ 1232411-41-4 ]

Yield	Reaction Conditions	Operation in experiment
56%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; acetonitrile; at 110℃; for 0.5h;Microwave irradiation;	5-bromo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (150 mg, 0.4715 mmol), <strong>[405520-68-5][4-(dimethylcarbamoyl)phenyl]boronic acid</strong> (91.00 mg, 0.4715 mmol), sodium carbonate (99.95 mg, 0.9430 mmol) and palladium; triphenylphosphane (54.48 mg, 0.04715 mmol) in a mixture of acetonitrile (1.5 mL) and water (1.5 mL) was heated at 1 10C in the microwave for 30 minutes. The reaction was diluted with water and EtOAc and the layers separated. The combined organics were dried (MgSO,j), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 12g column, 0- 100% EtO Ac/Petroleum ether) to give the desired product (102.8mg, 56% Yield). 1H NMR (400.0 MHz, DMSO) d 2.98 (6H, m), 7.55 (2H, m), 7.69-7.71 (3H, m), 7.83 (2H, br s), 8.17- 8.20 (4H, m), 9.00 (1H, s) ppm; MS (ES+) 387.13

Reference： [1]Patent: WO2010/71837,2010,A1 .Location in patent: Page/Page column 165

29
[ 912368-70-8 ]
[ 405520-68-5 ]
[ 1261302-37-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7216 - 7221

30
[ 1226791-82-7 ]
[ 405520-68-5 ]
[ 1268163-53-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium carbonate;palladium diacetate; bis(p-sulfonatophenyl)phenylphosphine dipotassium salt; In ethanol; water; at 65℃; for 1h;Inert atmosphere;	To Na2CO3 (129 mg, 1.214 mmol) in a 50 mL round-bottom flask was added water (3.7 mL) was bubbled with N2 for 10 min. To this mixture was added tert-butyl (lE,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate (200 mg, 0.40 mmol) in EtOH (4.9 mL) at room temperature. The resulting mixture was bubbled with N2 for 10 min. Pd(OAc)2 (9.3 mg, 0.040 mmol) and 4,4'-(phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate (45 mg, 0.081 mmol) were added. The resulting mixture was warmed to 65 0C with N2 bubbling. To this mixture was added a solution of 4-(dimethylcarbamoyl)phenylboronic acid (97 mg, 0.49 mmol) in EtOH (0.6 mL). The resulting mixture was stirred at 65 0C for 1 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give the crude material that was diluted with water (5 mL) and EtOAc (10 mL). The mixture was filtered through GF/F filter. The aqueous layer was separated and extracted with EtOAc (10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSOzj, filtered, and concentrated under reduced pressure to give the crude product that was purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2) to afford 178 mg (83%) of tert-butyl (lE,4E)-8-(4-(dimethylcarbamoyl)phenyl)-4- (dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate. MS APCI(+) m/z 533 (M+l) detected.
	With sodium carbonate;4,4'-(phenylphosphindene)bisbenzenesulfonic acid dipotassium; palladium diacetate; In water; acetonitrile; at 65℃; for 1h;Inert atmosphere;Product distribution / selectivity;	except in this case a co-solvent of MeCN-water (1.5:1) was used: To Na2CO3 (129 mg, 1.214 mmol) in a 50 mL round-bottom flask was added water (3.7 mL) was bubbled with N2 for 10 min. To this mixture was added tert-butyl (lE,4E)-8-bromo-4-(dipropylcarbamoyl)-3H- benzo[b]azepin-2-ylcarbamate (200 mg, 0.40 mmol) in EtOH (4.9 mL) at room temperature. The resulting mixture was bubbled with N2 for 10 min. Pd(OAc)2 (9.3 mg, 0.040 mmol) and 4,4'- (phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate (45 mg, 0.081 mmol) were added. The resulting mixture was warmed to 65 0C with N2 bubbling. To this mixture was added a solution of 4-(dimethylcarbamoyl)phenylboronic acid (97 mg, 0.49 mmol) in EtOH (0.6 mL). The resulting mixture was stirred at 65 0C for 1 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give the crude material that was diluted with water (5 mL) and EtOAc (10 mL). The mixture was filtered through GF/F filter. The aqueous layer was separated and extracted with EtOAc (10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSOzj, filtered, and concentrated under reduced pressure to give the crude product that was purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2).

Reference： [1]Patent: WO2011/22509,2011,A2 .Location in patent: Page/Page column 75
[2]Patent: WO2011/22508,2011,A2 .Location in patent: Page/Page column 75

31
[ 1251002-97-7 ]
[ 405520-68-5 ]
[ 1293995-90-0 ]