182344-13-4|(3-Chloro-4-hydroxyphenyl)boronic acid| Ambeed

Structure of 182344-13-4

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Quality Control of [ 182344-13-4 ] Purity: 98% SDS Specification

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Product Details of [ 182344-13-4 ]

CAS No. :	182344-13-4
Formula :	C₆H₆BClO₃
M.W :	172.37
SMILES Code :	OC1=CC=C(B(O)O)C=C1Cl
MDL No. :	MFCD09258739
InChI Key :	WWQIKFZZILXJHG-UHFFFAOYSA-N
Pubchem ID :	22125373

Safety of [ 182344-13-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 182344-13-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	3.0
Molar Refractivity	43.3
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	60.69 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.1
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.27
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.27
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.55
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.11

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.94
Solubility	1.98 mg/ml ; 0.0115 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.97
Solubility	1.86 mg/ml ; 0.0108 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.32
Solubility	8.16 mg/ml ; 0.0473 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.57 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.76

Application In Synthesis of [ 182344-13-4 ]

* 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.

Downstream synthetic route of [ 182344-13-4 ]

[ 182344-13-4 ] Synthesis Path-Downstream 1~35

1
[ 3964-56-5 ]
[ 182344-13-4 ]

Yield	Reaction Conditions	Operation in experiment
15%		3-chIoro-4-hydroxyphenylboronic acid 83. To a stirred solution of 4-bromo-2-chlorophenol (5 g5 24 mmol) in dry THF (75 mL)5 cooled to -780C5 was added slowly drop-wise n-BuLi (12 mL of a 2.44 M solution, 29 mmol) and the reaction was stirred at -78°C for 2 h. To this was then added trimethyl borate (3.3 mL, 29 mmol) and the reaction was allowed to warm slowly to r.t. with stirring for 19 h. The reaction was quenched with HCl (aq., 2 M) and the organics extracted into EtOAc (2 x 60 mL). These extracts were combined and concentrated under reduced pressure to give a white precipitate in an oily substance. To this was added hexane and the white powder was collected by filtration and washed with hexane. Yield 15percent: 1H NMR delta (270 MHz, DMSOd6) 6.49 (bs), 6.91 (IH5 d, J= 7.9 Hz)5 7.54 (IH, dd, J= 8.2, 1.5 Hz)5 7.72 (IH5 d, J= 1.5 Hz)5 8.02 (bs), 10.32 (IH, s); HPLC tr = 3.36 min (>91percent) 90percent MeCN in H2O; LC/MS (APCI) m/z 171.16 (M-H)-.
12 - 27%		3-ChIoro-4-hydroxyphenylboronic acid (TJA01187) C6H6BClO3 MW 172.37. A dry 250 ml r.b. flask was loaded with 4-bromo-2-chlorophenol (5.00 g, 24.1 mmol) and purged with N2(g). Anhydrous THF (100 mL) added with stirring and the vessel cooled to -78 0C (dry ice/acetone bath). After 30 mins n-BuLi, 2.3 M in hexanes, (12.9 mL, 28.9 mmol) was added dropwise over 20 min. The reaction was left to stir for 1 h. Triisopropyl borate (6.65 mL, 28.9 mmol) was added dropwise with the reaction still at -78 0C. After 15 min of stirring at this temperature the dry ice/acetone bath was removed. At about 0 0C 2 M HCl(aq) (5 mL) was added and the reaction left to stir for a further 15 min. THF removed under vacuum and residues taken up in ethyl acetate (50 mL). Distilled H2O (50 mL) was added and the organic layer separated. The aqueous layer was extracted with ethyl acetate (50 mL x 2). The organic portions were combined and washed with sat. Na2CO3 (aq). The aqueous layer was separated and treated with 2M HCl (aq) until the pH was about 4. This was then extracted with ethyl acetate (50 mL x 2). The organic portions were then dried over MgSO4 and solvent removed. The resultant off white residues were taken up in a minimum of ethyl acetate (2-3 mL) and added to dropwise to hexane (50 mL) with stirring. The white ppt was filtered to give the title compound as an off white solid (0.490 g, 12 percent).1H NMR (600 MHz, DMSO-^6) delta 6.89-6.92 (IH5 d, J= 8.2 Hz, ArH), 7.52-7.56 (IH5 dd, J= 1.8 7.9 Hz, ArH)5 7.72-7.73 (IH, d, J= 1.5 Hz5 ArH)5 7.98 (2H, s, ArB(OH)2) and 10.33 (IH5 s, ArOH); HPLC (70 percent CH3CN in H2O) ttau= 3.654 (97.92 percent); LCMS (APCI), m/z 173.11 (37ClM-- H5 15 percent)5 171.10 (35ClM"- H5 55), 129.05 ((37ClM" - H) - B(OH)2, 3O)5 127.04 ((35ClM- - H) - B(OH)2, 100).

References: [1]Patent: WO2007/96647,2007,A2 .Location in patent: Page/Page column 125-126.
[2]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 120-121; 148-149; 152-153; 154-155.
[3]Journal of the American Chemical Society,2007,vol. 129,p. 1894 - 1895.

2
[ 182344-13-4 ]
[ 14985-44-5 ]
8-(3-chloro-4-hydroxyphenyl)-2'-deoxyadenosine [ No CAS ]

References: [1]Journal of the American Chemical Society,2007,vol. 129,p. 1894 - 1895.

3
[ 182344-13-4 ]
[ 871116-69-7 ]
3-((1H-1,2,4-triazol-1-yl)methyl)-3'-chloro-4'-hydroxybiphenyl-4-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With tetrabutylammomium bromide; potassium carbonate;palladium diacetate; In ethanol; water; at 120℃; for 0.05h;	4'-Hydroxy-3'-chIoro-3-[l,2,4]triazol-l-ylmethyl-biphenyI-4-carbonitrile (TJA02027) C16HnClN4O MW 310.74. A 10 mL microwave vial was loaded with TJAO 1046 (0.150 g, 0.570 mmol), TJAO 1085 (0.118 g, 0.684 mmol), potassium carbonate (0.197 g5 1.43 mmol), tetrabutylammonium bromide (0.189 g, 0.570 mmol), Pd(OAc)2 (0.003-0.004 g, 2-3 mol V0), ethanol (1.5 mL) and distilled water (3.5 mL). The vial was sealed and loaded (with no prior degassing) into a CEM Explorer Microwave. After a run time of 3 min at 120 0C the reaction mixture was allowed to cool and ethyl acetate (50 mL) added. This was then washed with distilled water (30 mL x 3) and brine (30 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo to leave a yellow/brown residue. The crude product was purified via flash chromatography (20 g column, method4) eluted the title compound as a white solid (0.065 g, 37 percent),Rf. 0.44 (etitryl acetate);1H NMR (270 MHz, DMSCW6) delta 5.67 (2H, s, ArCH2N), 7.07-7.10 (IH, d, J= 8.4 Hz,ArH)5 7.52-7.56 (IH, dd, J= 2.2 8.2 Hz, ArH), 7.74-7.75 (IH, d, J= 2.2 Hz5 ArH), 7.80-7.83 (2H, m, ArH), 7.89-7.93 (2H, m, ArH C2H2N3), 8.04 (IH, s, C2H2N3) and 8.73(IH, s, ArOH);13C NMR (69.5 MHz, DMSO-J6) delta 51.1 (CH2), 110.0 (C), 117.7 (CH), 121.2 (C), 126.9(CH), 127.4 (CH), 128.1 (CH)5 128.9 (CH)5 130.1 (C)5 134.5 (CH), 140.0 (C), 144.0 (C),145.4 (CH)5 152.6 (CH) and 154.6 (C) (one overlapping signal);HPLC (90 percent CH3CN in H2O) ttau= 2.073 (98.19 percent);LCMS (APCI)5 m/z 312.66 (37ClM+ + H5 35 percent)5 310.64 (35ClM++ H5 100).

References: [1]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 155-156.
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 2155 - 2170.

4
[ 182344-13-4 ]
[ 757905-89-8 ]
2-(5-((1H-1,2,4-triazol-1-yl)methyl)-3'-chloro-4'-hydroxybiphenyl-3-yl)-2-methylpropanenitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With tetrabutylammomium bromide; potassium carbonate;palladium diacetate; In ethanol; water; at 150℃; for 0.0833333h;	2-(4'-Hydroxy-3-chloro-5-[l,2,4]triazol-l-ylmethyI-biphenyI-3-yl)-2-methyI-propionitrile (TJA01189) C19H17ClN4O MW 352.82. A 10 mL microwave vial was loaded with TJA01037 (0.200 g, 0.656 mmol), TJAOl 187 (0.136 g, 0.787 mmol), potassium carbonate (0.227 g, 1.64 mmol), tetrabutylammonium bromide (0.218 g5 0.656 mmol), Pd(OAc)2 (0.004-0.005 g, 2-3 mol percent), ethanol (1.5 mL) and distilled water (3.5 mL). The vial was sealed and loaded (with no prior degassing) into a CEM Explorer Microwave. After a run time of 5 min at 150 0C the reaction mixture was allowed to cool and ethyl acetate (50 mL) added. This was then washed with distilled water (30 mL x 3) and brine (30 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo to leave a yellow/brown residue. The crude product was purified via flash chromatography (20 g column, method4) to give a white solid (0.074 g). Recrystallisation (dichloromethane) gave the title compound as a white solid (0.175 g, 75 percent),R/. 0.19 (ethyl acetate). 1H NMR (270 MHz, DMSCW6) delta 1.72 (6H, s, ArC(CH3)2CN), 5.49 (2H, s, ArCH2N), 7.05-7.08 (IH, d, J= 8.4 Hz, ArH), 7.42-7.51 (3H, m, ArH), 7.64-7.68 (2H, m, ArH), 8.02 (IH, s, C2H2N3), 8.73 (IH, s, C2H2N3) and 10.44 (IH, s, ArOH);13C NMR (67.9 MHz, DMSO-cfe) .pound. 28.8 (CH3), 37.4 (C), 52.5 (CH2), 117.6 (CH), 120.9 (C), 123.1 (CH), 124.1 (CH), 125.1 (CH), 125.9 (CH), 127.1 (CH), 128.6 (CH), 131.9 (C), 138.2 (C)5 140.5 (C), 143.2 (C), 144.9 (CH), 152.4 (CH) and 153.6 (C); HPLC (90 percent CH3CN in H2O) ttau= 1.921 (94.06 percent); LCMS (APCI), m/z 353.40 (37ClMVH, 35 percent), 351.39 (35CEVr - H, 100).

References: [1]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 153-154.
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 2155 - 2170.

5
[ 182344-13-4 ]
[ 942154-61-2 ]
5-((1H-1,2,4-triazol-1-yl)methyl)-3'-chloro-4'-hydroxybiphenyl-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	With tetrabutylammomium bromide; potassium carbonate;palladium diacetate; In ethanol; water; at 150℃; for 0.0833333h;Irradiation;	4'-Hydroxy-3'-chIoro-3-[l,2,4]triazoI-l-ylmethyl-biphenyI-6-carbonitrile (TJA02038, STX2112) C16H11ClN4O MW 310.74. A 10 mL microwave vial was loaded with TJA01024 (0.150 g, 0.570 mmol), TJA02028 (0.147 g, 0.855 mmol), potassium carbonate (0.198 g, 1.43 mmol), tetrabutylammonium bromide (0.189 g, 0.570 mmol), Pd(OAc)2 (0.003-0.004 g, 2-3 mol percent), ethanol (1.5 mL) and distilled water (3.5 mL). The vial was sealed and loaded (with no prior degassing) into a CEM Explorer Microwave. After a run time of 5 min at 150 0C the reaction mixture was allowed to cool and ethyl acetate (50 mL) added. This was then washed with distilled water (25 mL x 3) and brine (25 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo to leave a yellow/brown residue. The crude product was purified via flash chromatography (20 g column, method4) to give a white solid (0.074 g). Recrystallisation (dichloromethane) gave the title compound as a white solid (0.026 g, 13 percent), mp 186.2-188.9 0C; Rf. 0.44 (ethyl acetate);1H NMR (270 MHz, DMSO-J6) delta 5.56 (2H, s, ArCH2N), 7.09-7.12 (IH, d, J= 8.4 Hz,ArH), 7.33-7.37 (2H, m, ArH), 7.52 (IH, s, ArH), 7.55-7.56 (IH, d, J= 2.2 Hz, ArH),7.90-7.92 (IH, d, J=7.9 Hz, ArH), 8.03 (IH, s, C2H2N3), 8.72 (IH, s, C2H2N3) and 10.67(IH, bs, ArOH);HPLC (70 percent CH3CN in H2O) ttau= 3.774 (97.17 percent);LCMS (APCI), m/z 311.08 (37ClM" - H, 30 percent), 309.13 (35ClM" - H, 100).

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 2155 - 2170.
[2]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 149-150.

6
[ 182344-13-4 ]
[ 942154-19-0 ]
[ 942154-44-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	With tetrabutylammomium bromide; potassium carbonate;palladium diacetate; In ethanol; water; at 120℃; for 0.05h;Irradiation;	3'-(l,254)Triazole-l-yI-methyI-biphenyl-3-ehloro-4-oI (TJA01191) C15Hi2ClN3O MW 285.73. A 10 mL microwave vial was loaded with TJA01009 (0.150 g, 0.630 mmol), TJA01187 (0.130 g, 0.756 mmol), potassium carbonate (0.218 g, 1.58 mmol), tetrabutylammonium bromide (0.209 g, 0.630 mmol), Pd(OAc)2 (0.004-0.005 g, 2-3 mol percent), ethanol (1.5 mL) and distilled water (3.5 mL). The vial was sealed and loaded (with no prior degassing) into a CEM Explorer Microwave. After a run time of 3 min at 120 0C the reaction mixture was allowed to cool and ethyl acetate (50 mL) added. This was then washed with distilled water (25 mL x 3) and brine (25 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo to leave a yellow/brown residue. The crude product was purified via flash chromatography (20 g column, method4) eluted the title compound as an off white solid (0.129 g, 72 percent), Rf. 0.35 (ethyl acetate). 1H NMR (270 MHz5 DMSO-J6) delta 5.46 (2H, s, ArCH2N), 7.04-7.07 (IH, d, J= 8.4 Hz, ArH), 7.18-7.20 (IH, d, J= 7.4 Hz, ArH)5 7.28-7.62 (5H, m, ArH)5 8.01 (IH5 s, C2H2N3), 8.71 (IH5 S5 C2H2N3) and 10.40 (IH5 bs, ArOH); HPLC (70 percent CH3CN in H2O) ttau= 4.274 (96.66 percent); LCMS (APCI), m/z 286.33 (37ClM--H5 30 percent), 284.32 (35ClM- - H5 100).

References: [1]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 121-122.
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 2155 - 2170.

7
[ 182344-13-4 ]
[ 99-90-1 ]
[ 106271-58-3 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrabutylammomium bromide; potassium carbonate;palladium diacetate; In ethanol; water; at 150℃; for 0.166667h;Irradiation;	l-(3'-ChIoro-4'-hydroxy-biphenyl-4-yl)-ethanone 84. To a mixture of 4'-bromoacetophenone (0.10Og, 0.5 mmol), 3-chloro-4- hydroxyphenylboronic acid 83 (0.103 g, 0.6 mmol), K2CO3 (0.173 g5 1.25 mmol) and Bu4NBr (0.161 g, 0.5 mmol) in EtOH (1.2 mL) and water (2.8 mL) was added Pd(OAc)2 (catalytic) and the reaction was micro waved at 15O0C for 10 min. Water (10 mL) was added and the organics extracted into EtOAc (10 mL). Flash chromatography using an elution gradient of hexane to 30percent EtOAc in hexane gave the product in a mixture. This was dissolved in EtOAc and extracted with base. The aqueous layer was acidified and organics extracted into EtOAc then concentrated under reduced pressure. Flash chromatography using DCM as eluent gave the product as the first fraction: 1H NMR delta (270 MHz5 CDCl3) 2.62 (3H, s), 5.86 (IH5 s), 7.11 (IH5 d5 J= 8.4 Hz), 7.44 (IH, dd, J= 8.4, 2.2 Hz), 7.57-7.62 (3H, m), 8.00 (2H5 d, J= 8.7 Hz); HPLC > 92percent (Rt 3.98, 90percent MeCN in H2O); ES-ve MS (M-H)- 245.22 m/z

References: [1]Patent: WO2007/96647,2007,A2 .Location in patent: Page/Page column 126.

8
[ 182344-13-4 ]
[ 1235468-21-9 ]
[ 1235468-23-1 ]

Yield	Reaction Conditions	Operation in experiment
34.9%	With potassium phosphate;palladium diacetate; XPhos; In tetrahydrofuran; at 80℃; for 3h;Microwave irradiation; Inert atmosphere;	A microwave vial containing a mixture of 3-chloro-4- hydroxyphenylboronic acid (64 mg, 0.37 mmol), methyl 2-bromo-7-(4- methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxylate (50 mg, 0.12 mmol), powdered potassium phosphate tribasic (116 mg, 0.546 mmol), 2- dicyclohexylphosphino-2',4',6'-tri-iso-propyl-l,r-biphenyl (12 mg, 0.025 mmol), and Pd(OAc)2 (2.8 mg, 0.012 mmol) was flushed with nitrogen. THF (0.5 mL) was added, the vial was sealed, and the reaction was heated at 80 °C for 3 hr. Preparative HPLC (100 x 30 mm Luna C18 column, Solvent A = 10percent Methanol, 90percent H2O, 0.1percent TFA; Solvent B = 90percent Methanol, 10percent H2O, 0.1percent TFA; 10 - 60percent B at 42 mL/min over 20 min) of the reaction mixture followed by SCX capture and release with 2 N NH3 in MeOH gave methyl 2-(3-chloro-4-hydroxyphenyl)-7-(4-methylpiperazin-1-yl)-5H- pyrido[3,2-b]indole-4-carboxylate (30 mg, 0.043 mmol, 34.9 percent yield. MS (ESI) m/z 451.10 (M+H).

References: [1]Patent: WO2010/80474,2010,A1 .Location in patent: Page/Page column 243.

9
[ 182344-13-4 ]
[ 1214320-05-4 ]
[ 1214320-19-0 ]

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 2155 - 2170.

10
[ 182344-13-4 ]
[ 1032822-28-8 ]
[ 1214320-23-6 ]

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 2155 - 2170.

11
[ 182344-13-4 ]
[ 1032822-31-3 ]
[ 1214320-25-8 ]

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 2155 - 2170.

12
[ 182344-13-4 ]
[ 1226341-15-6 ]
[ 1255939-97-9 ]

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 8176 - 8186.

13
[ 182344-13-4 ]
[ 1268826-55-6 ]
[ 1340482-24-7 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7547 - 7557.

14
[ 151239-47-3 ]
[ 182344-13-4 ]
[ 1357563-67-7 ]