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Chemical Structure| 89694-46-2 Chemical Structure| 89694-46-2

Structure of 89694-46-2

Chemical Structure| 89694-46-2

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Product Details of [ 89694-46-2 ]

CAS No. :89694-46-2
Formula : C7H8BClO3
M.W : 186.40
SMILES Code : COC1=CC(B(O)O)=C(Cl)C=C1
MDL No. :MFCD06659858
InChI Key :REFXAANPQCJZRY-UHFFFAOYSA-N
Pubchem ID :17750233

Safety of [ 89694-46-2 ]

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

Computational Chemistry of [ 89694-46-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 47.77
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

49.69 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.43
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.03
Log Po/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.

0.6
Log Po/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

-0.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.39

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.13
Solubility 1.37 mg/ml ; 0.00734 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.08
Solubility 1.56 mg/ml ; 0.00834 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

-2.03
Solubility 1.73 mg/ml ; 0.00927 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

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.42 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)

2.01

Application In Synthesis of [ 89694-46-2 ]

* 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 [ 89694-46-2 ]

[ 89694-46-2 ] Synthesis Path-Downstream   1~35

  • 1
  • m-Methoxy-benzolboronsaeureanhydrid [ No CAS ]
  • [ 89694-46-2 ]
  • 2
  • [ 89694-46-2 ]
  • 2-Chlor-5-methoxy-benzolboronsaeure-anhydrid [ No CAS ]
  • 4
  • [ 867330-26-5 ]
  • [ 89694-46-2 ]
  • [ 867330-72-1 ]
YieldReaction ConditionsOperation in experiment
84% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; for 4h;Heating / reflux; Example 50 Synthesis of 7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine 7-bromo-5-methyl-benzo[1,2,4]triazin-3-ylamine (33.47 mmol, 1.0 equiv), 1-chloro-4-methoxy-2-boronic acid (50.21 mmol, 1.5 equiv), Pd(PPH3)4 (3.347 mmol, 0.1 equiv), and Na2CO3 (133.9 mmol, 4.0 equiv) dissolved in DME/EtOH/water 6:1:1 and refluxed at 100° C. under an argon blanket for 4 h. The reaction was cooled to room temperature and diluted with 100 mL DCM and filtered. Precipitate recovered was suspended in water, filtered and rinsed with ether. Precipitate afforded product: 7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine, a green solid (8.37 g, 84percent yield). Rf=0.85 (9:1 DCM/MeOH). 1H NMR (DMSO-d6): delta 3.35 (s, 6H), 7.01 (dd, J=8.8 Hz, J=3.0, 1H), 7.09 (d, J=3.0 Hz, 1H), 7.48 (d, J=8.8 Hz, 1H), 7.75 (bm, 2H). MS (ES+) m/z=303. LC retention time 3.03 min.
  • 5
  • [ 745020-22-8 ]
  • [ 89694-46-2 ]
  • [ 298-12-4 ]
  • [ 918810-91-0 ]
YieldReaction ConditionsOperation in experiment
25% In N,N-dimethyl-formamide; acetonitrile; at 85℃; for 0.5h; A mixture of 2-chloro-5-methoxyhenylboronic acid (43 mg, 0.23 mmol), Intermediate 1 (72 mg, 0.2 mmol) and glyoxylic acid monohydrate (21 mg, 0.23 mmol) in acetonitrile (0.7 mL) and DMF (0.07 mL) was heated at 85° C. for 30 min in a Microwave Reactor. The crude product was purified by flash column chromatography (CH2Cl2:MeOH=100:15) to give 28 mg (25percent) of 77A as a solid. 1H NMR (400 MHz, Methanol-d4) delta ppm 1.16 (s, 18 H) 3.24 (s, 3 H) 5.55 (s, 1 H) 6.57 (d, J=2.20 Hz, 1 H) 6.75-6.84 (m, 2 H) 7.00 (d, J=3.08 Hz, 1 H) 7.10-7.20 (m, 1 H) 7.27 (d, J=9.23 Hz, 1 H) 7.32 (d, J=5.27 Hz, 1 H) 7.54 (d, J=9.23 Hz, 1 H) 7.93 (d, J=6.15 Hz, 1 H); LC MS 558 (M+H).
  • 6
  • [ 89694-46-2 ]
  • [ 1458-01-1 ]
  • [ 936249-15-9 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 70 - 75℃; for 2h; Method D To a suspension of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (10.9 g, 53.7 mmol) in 220 ml 1,4-dioxane and water (40 ml) was added 2-chloro-5-methoxybenzene boronic acid (20 g, 107 mmol), cesium carbonate (17.5 g, 53.7 mmol) and palladium tetrakis(triphenylphosphine) (620 mg, 0.54 mmol). The reaction was heated in an oil bath at 70-75° C. for 2 hours. The reaction was then cooled and poured into 500 ml water. The resulting slurry was stirred for 10 minutes before filtering under vacuum. The beige solid collected was then slurried in 100 ml methanol, stirred for 15 minutes, then filtered, washing the filter cake with methanol and vacuum drying to afford 17.4 g of the title product. 1H-NMR (d6-DMSO): NMR (DMSO): 3.65 (s, 3H), 3.75 (s, 3H), 6.4 (br s 2H), 6.9 (d, 1H), 7.0 (dd, 1H), 7.05 (br, s, 2H), 7.4 (d, 2H). LCMS Rt=3.74 min MS m/z 309 [MH]+
  • 7
  • [ 856851-34-8 ]
  • [ 89694-46-2 ]
  • [ 1079401-92-5 ]
YieldReaction ConditionsOperation in experiment
91% With sodium carbonate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In ethanol; water; toluene; at 20℃;Heating / reflux;Product distribution / selectivity; To 3-iodopyridine-2,6-diamine (Preparation 44, 3.0 g, 12.8 mmol), 5-methoxy-2- chlorophenylboronic acid (2.62 g, 14.0 mmol), sodium carbonate (1.49 g, 14.0 mmol), ethanol (15 ml), water (15 ml) and tris(dibenzylideneacetone)dipalladium (0) (175 mg,0.19 mmol) at ambient temperature under a nitrogen atmosphere was added tri- <n="142"/>terfbutylphosphine (1M in toluene, 0.574 ml, 0.574 mmol). The brown mixture was heated to reflux and maintained until reaction completion by HPLC. The reaction was cooled to ambient and the ethanol removed by vacuum distillation. 2- methyltetrahydrofuran (30 ml) was then added and the biphasic mixture filtered over arbocel.(TM)., extracted with saturated aqueous sodiumhydrogencarbonate (20 ml) and separated. The organic layer was extracted five times with 10percent w/v citric acid (20 ml), then to the combined aqueous layers was added 2-methyltetrahydrofuran (30 ml) then 5M sodium hydroxide until obtaining a pH>10. The layers were separated and the upper organic layer was concentrated to dryness in vacuo obtaining product as a beige solid 2.90 g (91percent yield).
55% With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; for 19h;Product distribution / selectivity; To a suspension of 3-iodopyridine-2,6-diamine (Preparation 44, 2 g, 8.51 mmol) in 1 ,4- dioxane (10 ml) and water (5 ml) was added <strong>[89694-46-2]2-chloro-5-methoxyphenyl boronic acid</strong> (0.793 g, 4.25 mmol), cesium carbonate (2.77 g, 8.51 mmol) and palladium tetrakis(triphenylphosphine) (0.123 g, 0.0125 mmol). The reaction was purged with nitrogen and heated at 80QC for 20 minutes. Three further portions of palladium tetrakis(triphenylphosphine) (0.123 g, 0.0125 mmol) and <strong>[89694-46-2]2-chloro-5-methoxyphenyl boronic acid</strong> (0.793 g, 4.25 mmol) were added at 20 minute intervals. The reaction was heated at 8O0C for 18 hours before concentrating in vacuo. The residue was taken up in ethyl acetate (20 ml) and washed with a saturated aqueous solution of brine (20 ml) before drying over Na2SO4 and concentrating in vacuo. The residue was purified by silica gel column chromatography, eluting with 50:50 to 100:0 ethyl acetate-.pentane to afford the title compound as a brown foam (1.157 g, 55percent yield). MS m/z 250 [MH]+1HNMR (CDCI3): 3.79 (s, 3H), 4.23 (br s, 2H), 4.32 (br s, 2H), 6.00 (d, 1 H), 6.86 (m,2H), 7.14 (d, 1 H), 7.38 (d, 1 H)
  • 8
  • [ 942438-82-6 ]
  • [ 89694-46-2 ]
  • 4-Amino-8-(2-chloro-5-methoxyphenyl)-7-fluoro-cinnoline-3-carboxylic acid propylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% EXAMPLE 92 4-Amino-8-(2-chloro-5-methoxyphenyl)-7-fluoro-cinnoline-3-carboxylic acid propylamide The title compound was prepared from 4-amino-7-fluoro-8-iodo-N-propylcinnoline-3-carboxamide (250 mg, 0.67 mmol) and <strong>[89694-46-2]2-chloro-5-methoxyphenyl boronic acid</strong> (279 mg, 1.50 mmol) according to Method A to afford a solid (181 mg, 72percent). 1H NMR (500.333 MHz, CDCl3) delta 8.41 (s, 1H), 7.90 (dd, J=9.1, 5.1 Hz, 1H), 7.49 (t, J=8.7 Hz, 1H), 7.41 (dd, J=6.9, 2.7 Hz, 1H), 6.94-6.92 (m, 2H), 3.79 (s, 3H), 3.44 (q, J=6.7 Hz, 2H), 1.65 (sextet, J=7.2 Hz, 2H), 0.99 (t, J=7.3 Hz, 3H). MS APCI, m/z=389/391 (M+H). HPLC 2.13 min.
  • 9
  • [ 89694-46-2 ]
  • [ 431942-67-5 ]
YieldReaction ConditionsOperation in experiment
With N-chloro-succinimide; In acetonitrile; at 20℃; Method 12B; Method 12A was used except NCS was substituted for NBS.
  • 10
  • [ 89694-46-2 ]
  • [ 190273-89-3 ]
  • [ 1234096-83-3 ]
YieldReaction ConditionsOperation in experiment
61% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; N,N-dimethyl-formamide; at 100℃; for 2h;Inert atmosphere; Synthesis of intermediate 2 6-(2-Chloro-5-methoxy~phenyi)-quinazolin-2- ylamine; To a solution of 2-chloro-5-methoxy boronic acid (14.42g, 77.34 mmol, 1.5eq), 6-Bromo-quinazolin~2~ylamine ( 11.55g, 51.56 mmol, leq) and Na2CO3 (21.86g, 206.23 mmol, 4eq) in a mixture of 120ml DMF/3ml EtOH/30m. H2O, was added 2.311g (5.16 mmol, 0.1 eq) of tetrakis(tpiphenylphospine) palladium. The reaction was refluxed(1000C) for 2 hours under argon. It was then cooled off to room temperature to extract the product by DCM and brine. The product is then washed with water and ether, then dried to give 9.010 g (32 mmol, 61percent) of a pale yellow powder.
  • 11
  • [ 89694-46-2 ]
  • [ 7148-34-7 ]
  • [ 1112986-04-5 ]
YieldReaction ConditionsOperation in experiment
A stream of nitrogen gas was bubbled through a mixture of 4,8- dichloroquinazoline (1.75 g, 8.8 mmol), <strong>[89694-46-2]2-chloro-5-methoxyphenylboronic acid</strong> (1.97 g, 10.6 mmol), 2M aqueous Na2CO3 (11 mL, 22 mmol) in dimethoxyethane (15 mL) and water (4 mL) for 10 min. Tetrakis-triphenylphosphine palladium (521 mg, 0.44 mmol) was added and the mixture was stirred at 75 0C for 6 h. The suspension was cooled and partitioned between EtOAc (60 mL) and water (30 mL). The layers were separated and the organic layer was further washed with aqueous NaHCO3 (10 mL), water (10 mL), and brine (20 mL). The organic layer was dried with Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with a gradient of 0:100 to 20:80 E:H to afford white foamy solid. MS (ESI) m/z 305.0; HRMS: calcd for CI5HI0CI2N2O + H+, 305.02429; found (ESI, [M+H]+ Obs'd), 305.0247.
  • 12
  • [ 947248-68-2 ]
  • [ 89694-46-2 ]
  • [ 1239954-94-9 ]
YieldReaction ConditionsOperation in experiment
90% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; N,N-dimethyl-formamide; for 2h;Reflux; Inert atmosphere; To a solution of 2-Ch.oro-5-methoxy-phenylboronic acid (3.38g, 22.5 mmol, 1.5eq), 6- Bromo-[l,2,4]triazolo[l,5-a]pyridin-2-ylamine (3.2g, 15 mmol, leq) and Na2CO3 (6.36g, 60 mmol, 4eq) in a mixture of 40ml DMF/10ml EtOH/lOml H2O, was added 1.733g (1.5 mmol, 0.1 eq) of tetrakis(triphenylphospine) palladium. The reaction was refluxed for 2 hours under argon. It was then cooled off to room temperature and the product was precipitated by water, filtered, rinsed with water, ether and pentane to give a pale yellow powder (3.21 g, 13 mmol, 90percent yield).
90% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; N,N-dimethyl-formamide; for 2h;Reflux; Inert atmosphere; Method 1 :Synthesis of intermediate 1 : 6-(2-Chloro-5-methoxy-phenyl)-[1 ,2,4]triazolo[1 ,5- a]pyridin-2-ylamineTo a solution of 2-Chloro-5-methoxy-phenylboronic acid (3.38g, 22.5 mmol, 1 .5eq), 6- Bromo-[1 ,2,4]triazolo[1 ,5-a]pyridin-2-ylamine (3.2g, 15 mmol, 1 eq) and Na2C03 (6.36g, 60 mmol, 4eq) in a mixture of 40ml DMF/10ml EtOH/10ml H20, was added 1 .733g (1 .5 mmol, 0.1 eq) of tetrakis(triphenylphospine) palladium. The reaction was refluxed for 2 hours under argon. It was then cooled off to room temperature and the product was precipitated by water, filtered, rinsed with water, ether and pentane to give a pale yellow powder (3.21 g, 13 mmol, 90percent yield).
  • 13
  • [ 56-05-3 ]
  • [ 89694-46-2 ]
  • [ 915070-17-6 ]
  • 14
  • [ 1112985-72-4 ]
  • [ 89694-46-2 ]
  • [ 1112985-71-3 ]
  • [ 1112985-74-6 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 100℃; for 2h; Step 4: 4-(2-chloro-5-methoxyphenyl)-2-methyl-8-(trifluoromethyl)quinazoline A mixture of 2-methyl-8-(trifluoromethyl)quinazolin-4-yl trifluoromethanesulfonate (2.7 g, 7.5 mmol), <strong>[89694-46-2]2-chloro-5-methoxyphenylboronic acid</strong> (1.6 g, 9.4 mmol), K3PO4 (4.0 g, 18.8 mmol) and Pd(PPh3)4 (433 mg, 0.4 mmol) in dioxane (25 mL) was heated at 100° C. for 2 h. The mixture was poured into a mixture of EtOAc (100 mL) and water (70 mL) and the layers were separated. The organic layer was washed with NaHCO3 (2*50 mL), water (50 mL), and brine (70 mL). The solution was concentrated and the residue was redissolved in ~15 mL of DCM. The solution was filtered (900 mg of 2-methyl-8-(trifluoromethyl)quinazolin-4(3H)-one was recovered) and the supernatent was added to a column of SiO2 which was eluted with a gradient of 0:100 to 20:80 EtOAc:Hex. The product was isolated as a white foam. MS (ES) m/z 352.9; HRMS: calcd for C17H12ClF3N2O+H+, 353.06630; found (ESI, [M+H]+ Obs'd), 353.0668.
  • 15
  • [ 608-30-0 ]
  • [ 89694-46-2 ]
  • [ 1257236-13-7 ]
YieldReaction ConditionsOperation in experiment
47% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 150℃; for 1h;Microwave irradiation; <strong>[89694-46-2]2-chloro-5-methoxyphenylboronic acid</strong> (1.25 g, 6.71 mmol), 2,6-dibromoaniline (1.851 g, 7.38 mmol), sodium carbonate (6.71 mL, 13.41 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.465 g, 0.40 mmol) were dissolved in dioxane (10 mL), degassed and sealed into a microwave tube. The reaction was heated to 1500C for 1 hour in the microwave reactor and cooled to room temperature.The reaction mixture was poured into saturated aqueous NH4CI solution (100 mL), extracted with EtOAc (100 mL), and the organic layer was washed with water (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford an orange oil. The crude product was purified by flash silica chromatography, elution gradient 0 to 10percent EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 3-bromo-2'- chloro-5'-methoxybiphenyl-2-amine (0.993 g, 47 percent) as a white solid; 1H NMR (400 MHz, CDCI3) delta 3.73 (3H, s), 3.95 (2H, s), 6.61 (1 H, t), 6.73 - 6.78 (1 H, m), 6.83 (1 H, d), 6.92 - 6.94 (1 H, m), 7.31 - 7.34 (1 H, m), 7.38 - 7.40 (1 H, m)
  • 16
  • [ 89694-46-2 ]
  • [ 16499-66-4 ]
  • [ 1112985-56-4 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 80℃; for 6h;Inert atmosphere; Example 47 4-(2-chloro-5-methoxyphenyl)-8-(trifluoromethyl)quinazoline A stream of nitrogen gas was bubbled through a mixture of 4-chloro-8-(trifluoromethyl)quinazoline (660 mg, 2.83 mmol), <strong>[89694-46-2]2-chloro-5-methoxyphenylboronic acid</strong> (723 mg, 4.26 mmol), 2M aqueous Na2CO3 (4.25 mL, 8.5 mmol) in dimethoxyethane (8 mL) for 10 min. Tetrakis-triphenylphosphine palladium (168 mg, 0.14 mmol) was added and the mixture was stirred at 80° C. for 6 h. The suspension was cooled and poured into a mixture of EtOAc (60 mL) and water (30 mL). The layers were separated and the organic layer was further washed with aqueous NaHCO3 (10 mL), water (10 mL), and brine (20 mL). The organic layer was dried with Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography eluding with a gradient of 0:100 to 20:80 E:H to afford white foamy solid (640 mg). MS (ES) m/z 338.7; HRMS: calcd for C16H10ClF3N2O+H+, 339.05065; found (ESI, [M+H]+ Obs'd), 339.0510.
  • 17
  • [ 1260215-37-9 ]
  • [ 89694-46-2 ]
  • [ 1260215-96-0 ]
YieldReaction ConditionsOperation in experiment
5% With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; ethanol; water; at 150℃; for 0.5h;Microwave irradiation; Example 485-(4-Ammo-2-cyclopropyl-5-methyl-2H-imidazoI-2-yI)-2'-chloro-5'-methoxybiphenyI-2-ol2-Chloro-5-methoxyphenylboronic acid (93 mg, 0.50 mmol), 4-(4-amino-2-cyclopropyl-5-methyl-2H-imidazol-2-yl)-2-bromophenol (153.5 mg, 0.50 mmol), [1,1'- bis(diphenylphosphino)ferrocene]palladium(II) chloride (20.49 mg, 0.02 mmol), cesium carbonate (487 mg, 1.49 mmol) and DMErEtOH: Water 6:3:1 (4.00 mL) were put in a microwave vial and irradiated in a microwave reactor at 150 0C for 30 min, and then concentrated in vacuo. Dichloromethane and methanol were added to the residue and the resulting mixture was filtered through a syringe filter. The filtrate was concentrated in vacuo And the residue purified by silica chromatography using 0percent to 10percent (3.5 M ammonia in methanol) in dichloromethane. The desired fractions were pooled and concentrated in vacuo and purified by preparative HPLCto give 5-(4-amino-2-cyclopropyl-5-methyl-2H-imidazol-2-yl)-2'-chloro-5'-methoxybiphenyl-2-ol (9.80 mg, 5percent yield): 1H NMR (500 MHz, DMSO-J6) delta ppm 9.36 (br. s., 1 H), 7.34 - 7.41 (m, 2 H), 7.24 (d, 1 H), 6.92 (dd, 1 H), 6.80 (dd, 2 H), 6.36 (br. s., 2 H), 3.75 (s, 3 H), 2.12 (s, 3 H), 1.37 - 1.45 (m, 1 H), 0.24 - 0.33 (m, 2 H), 0.14 - 0.22 (m, 1 H), -0.07 - 0.00 (m, 1 H); MS (ES-) m/z 368 [M-H]"; MS (ES+) m/z 370 [MH-H]+.
  • 18
  • [ 89694-46-2 ]
  • [ 151266-23-8 ]
  • 3-(2-chloro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
16% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; N,N-dimethyl-formamide; at 80℃; for 12.5h;Inert atmosphere; Intermediate 873-(2-chloro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine To a solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.0770 g, 4.12 mmoles) in DMF (10 ml), ethanol (5 ml) and water (5 ml), 2-chloro-5-methoxyphenyl boroinc acid (1.00 g, 5.364 mmoles) and sodium carbonate (2.186 g, 20.63 mmoles) were added and the system is degassed for 30 min. Tetrakis triphenylphosphine Palladium (0.905 g, 0.783 mmoles) was added under nitrogen atmosphere and heated to 80° C. After 12 h, the reaction mixture was celite filtered, concentrated and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with methanol:dichloromethane to afford the title compound as green solid (0.090 g, 16percent yield). 1H-NMR (delta ppm, DMSO-d6, 400 MHz): delta 13.61 (s, 1H), 8.19 (s, 1H), 7.51 (d, J=8.9 Hz, 1H), 7.09 (d, J=8.9 Hz 1H), 7.06 (d, J=2.6 Hz 1H), 3.78 (s, 3H).
  • 19
  • [ 89694-46-2 ]
  • [ 1300584-91-1 ]
  • 20
  • [ 89694-46-2 ]
  • [ 1300584-92-2 ]
  • 25
  • [ 89694-46-2 ]
  • [ 1239954-96-1 ]
  • 26
  • [ 89694-46-2 ]
  • [ 1352930-19-8 ]
  • 27
  • [ 89694-46-2 ]
  • [ 190273-89-3 ]
  • [ 1239954-94-9 ]
YieldReaction ConditionsOperation in experiment
61% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; N,N-dimethyl-formamide; at 100℃; for 2h;Inert atmosphere; Method 2:Synthesis of intermediate 5: 6-(2-Chloro-5-methoxy-phenyl)-quinazolin-2- ylamineTo a solution of 2-chloro-5-methoxy boronic acid (14.42g, 77.34 mmol, 1 .5eq), 6-Bromo-quinazolin-2-ylamine (1 1 .55g, 51 .56 mmol, 1 eq) and Na2C03 (21 .86g, 206.23 mmol, 4eq) in a mixture of 120ml DMF/30ml EtOH/30ml H20, was added 2.31 1 g (5.16 mmol, 0.1 eq) of tetrakis(triphenylphospine) palladium. The reaction was refluxed (Iota OmicronOmicron ') for 2 hours under argon. It was then cooled off to room temperature to extract the product by DCM and brine. The product is then washed with water and ether, then dried to give 9.010 g (32 mmol, 61 percent) of a pale yellow powder.
  • 28
  • [ 89694-46-2 ]
  • [ 2401-25-4 ]
YieldReaction ConditionsOperation in experiment
With chloroamine-T; sodium iodide; In methanol; water; at 20℃; for 0.25h;flask wrapped with aluminum foil; To a 250ml round-bottom flask wrapped with aluminum foil was added a solution of 2-chloro-5- methoxy-phenyl boronic acid (5g, 26.82mmol) in 50percent MeOH/H20 (100ml). A solution of Nal (5.57g, 33.5 mmol) in water (34ml) and a solution of Chloramine-T (18.9g, 67.1mmol) in 50percent MeOH/H20 (34ml) were added to the mixture while stirring. Stirring was continued for 15 min at rt, followed by treatment with water and extraction with diethyl ether. The organic extraction was washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography with 10percent EtOAc in hexane to afford the desired product contaminated with EtOAc (8.6g).
  • 29
  • [ 89694-46-2 ]
  • [ 1400704-11-1 ]
  • 30
  • [ 89694-46-2 ]
  • [ 1400704-12-2 ]
  • 31
  • [ 89694-46-2 ]
  • [ 1400704-48-4 ]
  • 32
  • [ 89694-46-2 ]
  • C25H28ClN5O5S [ No CAS ]
  • 33
  • [ 578-66-5 ]
  • [ 89694-46-2 ]
  • [ 1644565-60-5 ]
  • 34
  • [ 10365-98-7 ]
  • [ 89694-46-2 ]
  • 35
  • [ 213745-17-6 ]
  • [ 89694-46-2 ]
  • 4-chloro-5-(2-chloro-5-methoxyphenyl)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 95℃; for 48h;Inert atmosphere; lb (210 mg, 0.62 mmol) was combined with <strong>[89694-46-2](2-chloro-5-methoxyphenyl)boronic acid</strong> (0266) (175 mg, 0.94 mmol), Tetrakis(triphenylphosphine)palladium (72 mg, 0.062 mmol), and potassium carbonate (173 mg, 1.25 mmol). Upon purging with argon gas the mixture was dissolved in a 4: 1 mixture of degassed dioxane/DI water (0.25M) and kept inert argon atmosphere. The reaction mixture was then heated at, 95°C for 48 h. Volatiles were then evaporated in vacuo and the reaction mixture was dissolved in 4:6 DI watenethyl acetate and the organic layer was collected and concentrated. The organic extract was then purified using FCC (gradient of hexanes: ethyl acetate 95 :5 to 80:20) to yield 39 mg of an orange oil in 35percent Yield. NMR (599 MHz, CDCh) delta 8.64 (s, 1H), 7.37 (d, J= 8.8 Hz, 1H), 7.33 (s, 1H), 6.95 (d, J= 3.0 Hz, 1H), 6.88 (dd, J = 8.8, 3.1 Hz, 1H), 5.32 - 5.26 (m, 1H), 3.82 (s, 3H), 2.36 - 2.24 (m, 2H), 2.05 - 1.89 (m, 4H), 1.86 - 1.76 (m, 2H). 13C NMR (151 MHz, CDCh) delta 157.68, 152.10, 151.00, 150.39, 132.80, 129.87, 126.46, 125.96, 1 18.38, 1 15.81, 1 14.88, 1 13.13, 55.93, 55.57, 32.89, 24.13.
 

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