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Structure of 214360-60-8

Chemical Structure| 214360-60-8

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Product Details of [ 214360-60-8 ]

CAS No. :214360-60-8
Formula : C14H20BNO3
M.W : 261.12
SMILES Code : CC(NC1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1)=O
MDL No. :MFCD02093722
InChI Key :ANGKVUVZQVUVJO-UHFFFAOYSA-N
Pubchem ID :2734619

Safety of [ 214360-60-8 ]

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

Computational Chemistry of [ 214360-60-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 77.23
TPSA ?

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

47.56 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

2.08
Log Po/w (WLOGP)?

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

1.75
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.

1.13
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

1.46
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.28

Water Solubility

Log S (ESOL):?

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

-2.81
Solubility 0.409 mg/ml ; 0.00157 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.

-2.71
Solubility 0.511 mg/ml ; 0.00196 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

-4.39
Solubility 0.0107 mg/ml ; 0.000041 mol/l
Class?

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

Moderately 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

Yes
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

Yes
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

0.0
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<0.0
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)

2.7

Application In Synthesis of [ 214360-60-8 ]

* 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 [ 214360-60-8 ]

[ 214360-60-8 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 32578-30-6 ]
  • [ 25015-63-8 ]
  • [ 214360-60-8 ]
  • 2
  • [ 214360-60-8 ]
  • [ 500314-09-0 ]
  • 3-[10-(4-acetylamino-phenyl)-anthracen-9-yl]-5-methyl-isoxazole-4-carboxylic acid ethyl ester [ No CAS ]
  • 3
  • [ 214360-60-8 ]
  • [ 500314-10-3 ]
  • 3-[10-(4-acetylamino-phenyl)-anthracen-9-yl]-5-methyl-isoxazole-4-carboxylic acid ethyl ester [ No CAS ]
  • 4
  • [ 591-87-7 ]
  • [ 214360-60-8 ]
  • [ 104699-52-7 ]
  • 5
  • [ 21040-45-9 ]
  • [ 214360-60-8 ]
  • (E)-3-(4-acetamidophenyl)-1-phenylpropene [ No CAS ]
  • 6
  • [ 76644-52-5 ]
  • [ 214360-60-8 ]
  • <i>N</i>-(4-cyclohex-2-enyl-phenyl)-acetamide [ No CAS ]
  • 7
  • [ 533-58-4 ]
  • [ 214360-60-8 ]
  • [ 108779-65-3 ]
  • 8
  • [ 54245-42-0 ]
  • [ 214360-60-8 ]
  • C8(11)CH11NO [ No CAS ]
  • 9
  • [ 108-24-7 ]
  • [ 214360-73-3 ]
  • [ 214360-60-8 ]
YieldReaction ConditionsOperation in experiment
87% In dichloromethane; at 20℃; for 10h; To a mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.0 g, 13.7 mmol) in DCM (70mL), was added acetic anhydride (7.0 g, 68.5 mmol). The reaction mixture was stirred at RT for 10 h. It was then concentrated under reduced pressure and the resulting residue was purified by flash column chromatography over silica gel (PE/EA 1:1, v/v) to give N-(4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl) acetamide as a yellow solid (3.1 g, 87%). LC-MS (ESI): m/z (M+1)+ = 262.31.
  • 10
  • Pd(dppf)2Cl2 [ No CAS ]
  • [ 19524-06-2 ]
  • [ 214360-60-8 ]
  • [ 59656-60-9 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In tetrahydrofuran; Step 1: N-(4-(4-pyridyl)phenyl)acetamide A round bottom flask was charged with a 2 N Na2CO3 solution (4 equivalents) and THF and the mixture was sparged with N2 through a dispersion tube. 4-Bromopyridine hydrochloride (1 equivalent) and N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamide (1.2 equivalents) were subsequently added, followed by Pd(dppf)2Cl2 (2.5 mol %). The reaction mixture was refluxed overnight, cooled to room temperature and diluted with EtOAc. The two phases were separated and the organic phase was washed with a 2 N Na2CO3 solution, brine, and dried (Na2SO4). Evaporation of the solvent under reduced pressure and purification by silica gel chromatography afforded the desired product as a white solid. MH+=213.1.
  • 11
  • [ 214360-60-8 ]
  • [ 333303-22-3 ]
  • ethyl 6-(4-acetamidophenyl)-7-(diethylamino)-2-oxo-2H-chromene-3-carboxylate [ No CAS ]
  • 12
  • [ 586-78-7 ]
  • [ 214360-60-8 ]
  • [ 28533-02-0 ]
  • 13
  • [ 104-92-7 ]
  • [ 214360-60-8 ]
  • [ 2221-22-9 ]
  • 14
  • [ 72601-11-7 ]
  • [ 214360-60-8 ]
  • N-[4-(2,2-dimethyl-5-oxo-2,5-dihydrofuran-3-yl)phenyl]acetamide [ No CAS ]
  • 15
  • [ 103-90-2 ]
  • C6H5CH2OCONHCH2COX [ No CAS ]
  • [ 214360-60-8 ]
  • 16
  • [ 214360-60-8 ]
  • [ 476477-23-3 ]
  • [ 700871-94-9 ]
YieldReaction ConditionsOperation in experiment
70% Into a 10 mL round bottom is placed the product of Preparation 9 (0. 0782G, 0. 2MMOL), N- [4- (4, 4,5, 5-TETRAMETHYL- [1, 3,2] dioxaborolan-2-yl) phenyl] acetamide (0.104 g, 0.4 mmol), 2 mL dioxane, and 1 mL 2M K2CO3. The mixture is heated in oil bath at 110 C FOR few minutes to dissolve organic reagents. A reflux condenser is positioned and the mixture is evacuated and purged with nitrogen several times. To the mixture is added Pd2 (dba) 3 (0.007 g, 0.006 mmol) and triphenylphosphine (0.007 g, 0.024 mmol) and the evacuating and purging with nitrogen repeated. The reaction mixture is heated in an oil bath at 110 C for 3 h. The mixture is cooled, extracted, and purified as in Example 1 to give the titled product (0.095 g, 70% yield). MS ES+ 446 (M+1)
  • 17
  • [ 622-50-4 ]
  • [ 25015-63-8 ]
  • [ 214360-60-8 ]
YieldReaction ConditionsOperation in experiment
81%Chromat. With triethylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 80℃; for 5h; [00168] To 25 mg PdCl2(dppf).CH2Cl2 in a reaction tube under nitrogen were added 4 ml dioxane, 0.43 ml (3 mmol) triethylamine, 0.47 ml (3.2 mmol) pinacolborane and 262 mg (1.0 mmol) p-iodoacetanilide. The p-iodoacetanilide did not react with the pinacolborane to liberate hydrogen. The reaction solution was warmed to 80 C. with stirring in an oil bath. After 1 h the solution had darkened and an aliquot (0.3 ml) was removed from the reaction solution, extracted into diethyl ether, washed several times with water and analysed by gc (fid detector, SGE HT5 capillary column). There was only one strong peak (of area 74% of total peak areas, uncorrected for response factors) in the gc and that was shown by gc/ms to be due to the desired arylboronic acid pinacol ester. On heating the reaction mixture for a further 4 h at 80 C., the apparent yield of the required boronic acid ester increased to 81% while that of the acetanilide and phenylboronic acid pinacol ester peak areas were 14% and 3.4% respectively.
90%Chromat. [00240] The catalyst amount in this reaction was reduced to approx. {fraction (1/35)} that used in the small scale reactions. The molar ratio of catalyst:iodide:pinacolborane:NEt3 is 1:1150:1500:2933. The amount of pinacolborane was 1.25 equivalents compared to the iodide. The pinacolborane was made from BH3?e2 by reaction with pinacol in dioxane. 50 ml of BH3?e2 were dissolved in 100 ml of dioxane in a 1 L Schlenk flask. To this was added dropwise 63.0 g of pinacol in 140 ml dioxane. After the addition was complete the solution was stirred at room temp. and then at 60 C. to ensure complete reaction of the BH3?e2. The solution contained a little white precipitate. [00241] The catalyst was activated prior to use by heating 1500 mg of PdCl2[dppf].CH2Cl2 with 30 ml of triethylamine in 370 ml dioxane at 80 C. from for 7.5 h. 67 ml of this dark brown solution was used in the reaction. [C00065] [00242] To the pinacolborane solution was added 120 ml (863 mmol) dry triethylamine, 92 g (352.5 mmol) p-iodoacetanilide and then 67 ml of the catalyst solution. The reaction solution was placed in the oil bath at 80 C. The solution became clear and pale brown in colour and after about 1 to 2 h, a precipitate of the amine.HI salt separated. After 5 h the reaction was over 90% complete. Heating was continued for several more hours after which no starting material was observed, by gc, to be in the reaction solution. The reaction product in a number of such reactions was always over 90% by gc, the only side product observed was acetanilide. No phenylboronic acid pinacol ester were seen in the gc unless very strong solutions were employed. [00243] The crude product was isolated by removing the amine salt from the solution at room temp. The excess pinacolborane was destroyed with dry methanol. After reducing the volume of the reaction solution, the product was precipitated with petroleum ether. The dark coloured impurity in the product was removed by passing a solution of the product in toluene through a short column of Merck type 9385.1000 silica gel 60. The product was obtained as a white solid, mp>162 C. from toluene. [00244] The presence of borane methyl sulfide complex in these reactions does not stop the reaction from progressing. It can retard rate of the reaction somewhat but indications are that it can retard, especially with certain substrate, the dehalogenation reaction to a greater extent than the boronation reaction and so lead to an increase in product yield.
  • 18
  • [ 19524-06-2 ]
  • [ 214360-60-8 ]
  • [ 59656-60-9 ]
YieldReaction ConditionsOperation in experiment
74% Compound 98 was prepared by a procedure similar to that of Cai and co-workers.22 A mixture of 4-acetamidophenylboronic acid pinacol ester (91) (0.10 g, 0.38 mmol), 4bromopyridine hydrochloride (92) (89 mg, 0.46 mmol) and sodium hydrogen carbonate (0.14 g, 1.61 mmol) in toluene (2 mL), ethanol (1 mL) and water (0.5 mL) was flushed with argon for 15 min. To this mixture was added bis(triphenylphosphine)palladium(II) chloride (14 mg, 0.02 mmol) and the resulting mixture heated under microwave irradiation (50 W) at 120 C for 1 h. The reaction was allowed to cool, diluted with dichloromethane (50 mL), washed with water (50 mL), the separated aqueous layer further extracted with dichloromethane (2 × 50 mL), and the combined organic phases dried over anhydrous magnesium sulfate, filtered and the solvent removed in vacuo. Purification by flash chromatography (hexane:ethyl acetate, 4:1) afforded 98 as a pale brown solid (60 mg, 0.28 mmol, 74%). Rf = 0.20 (hexane:ethyl acetate, 1:4). mp 195-200 C; 1H NMR (400MHz; CDCl3) deltaH 2.18 (3H, s, CH3), 3.82 (1H, s, NH), 7.54 (2H, dd, J = 6.4 Hz, J = 1.8 Hz, H-3, H-5), 7.60-7.70 (4H, m, H-2', H-3', H-5', H-6') and 8.55 (2H, d, J = 6.0 Hz, H-2, H-6); 13C NMR (100MHz, CDCl3) deltaC 23.6 (CH3), 120.1 (CH), 121.3 (CH), 127.2 (CH), 132.6 (C), 139.5 (C), 148.3 (C), 149.2 (CH) and 169.8 (C); IR (numax/cm-1) 651, 807, 1225, 1302 (C-N), 1324, 1489, 1530, 1556, 1596 (N-H), 1661 (C=O), 3034 and 3302 (N-H); MS (ESI, 70 eV) m/z 213 (M+, 100%); Found (M+, 213.1029), C13H13N2O requires 213.1022.
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; dichloromethane;Heating / reflux; A round bottom flask was charged with a 2 N Na2CO3 solution (4 equivalents) and THF and the mixture was sparged with N2 through a dispersion tube. 4-Bromopyridine hydrochloride (1 equivalent) and N- [4- (4,4, 5, 5-TETRAMETHYL-1, 3, 2-dioxaborolan-2-yl) phenyl] acetamide (1.2 equivalents) were subsequently added, followed by Pd (DPPF) 2CI2 (2.5 mol %). The reaction mixture was refluxed overnight, cooled to room temperature and diluted with EtOAc. The two phases were separated and the organic phase was washed with a 2 N NA2CO3 solution, brine, and dried (NA2S04). Evaporation of the solvent under reduced pressure and purification by silica gel chromatography afforded the desired product as a white solid. MH+ = 213.1.
  • 19
  • [ 214360-60-8 ]
  • [ 209808-18-4 ]
  • C30H39N3O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 90℃; INTERMEDIATE 7 : 4- [f4- (acetvlamino) phenyll-4-piperidinvlidenemethvll- N, N-diethvl-benzamide; To a flask containing INTERMEDIATE 5 (5.04 g, 11.2 mmol) was added toluene (100 mL), ethanol (100 mL), 2.0 M sodium carbonate (35 mL, 70 mmol) and 4'- (4,4, 5, 5-tetramethyl-1, 3,2-dioxaborolan-2-yl) acetanilide (4.39 g, 16.8 mmol). The solution was degassed for 20 minutes and then palladium tetrakistriphenylphosphine (1.28 g, 1.06 mmol) was added. The reaction mixture was heated to 90 C and was stirred overnight under an atmosphere of nitrogen. The reaction mixture was concentrated in vacuo and the residue was diluted with ethyl acetate. The solution was washed with two portions of brine and the organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash chromatography, eluting 0% to 100% ethyl acetate in hexanes, to yield the BOC-protected intermediate as a brown solid. The solid was dissolved in dichloromethane (40 mL) and trifluoroacetic acid (10 mL) was added. The reaction was stirred overnight at room temperature. Saturated aqueous sodium bicarbonate was slowly added until bubbling ceased. The layers were separated and the organic layer was washed with one portion of saturated aqueous sodium bicarbonate and then one portion of brine. The organic layer was dried (Na2S04), filtered and concentrated to give INTERMEDIATE 7 (4.42 g, 98%) as a brown solid. (400 MHz, CDC13) 8 1.08-1. 18 (m, 3H), 1.19-1. 28 (m, 3H), 2.12- 2.16 (s, 3H), 2.29-2. 41 (m, 5H), 3.23-3. 35 (m, 2H), 3.47-3. 59 (m, 2H), 7.00 (d, J = 8.40 Hz, 2H), 7.11 (d, J = 8.20 Hz, 2H), 7.29 (d, J = 8. 20 Hz, 2H), 7.41 (d, J = 8. 59 Hz, 2H).
  • 20
  • [ 855291-58-6 ]
  • [ 214360-60-8 ]
  • [ 855738-65-7 ]
YieldReaction ConditionsOperation in experiment
79% With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; CyJohnPhos; In 1,4-dioxane; ethanol; water; at 150℃; for 0.166667h;Microwave; Example 33B (R)-N-{4-[6-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-pyridazin-3-yl]-phenyl}-acetamide Trifluoroacetate The product of Example 33A (182 mg, 0.76 mmol) was coupled with <strong>[214360-60-8]N-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetamide</strong> (TCl, 500 mg, 1.9 mmol) under the catalysis of dichlorobis(triphenylphosphine)palladium (II) (Aldrich, 53 mg, 0.076 mmol) and 2-(dicyclohexylphosphino)biphenyl (Strem Chemicals, 6.5 mg, 0.019 mmol) in 1 mL each of ethanol, p-dioxane, and 1 M aq. sodium carbonate at 150' C. at 330 watts for 10 min in an Emry Creator microwave. The mixture was cooled to room temperature, filtered through Celite, and concentrated onto silica. The product was purified by column chromatography (SiO2, 5% methanol containing 1% NH4OH-CH2Cl2) to provide a free base of the title compound as solid (203 mg, 79%), which was dissolved in methanol (0.8 mL) containing trifluoroacetic acid (75 mg, 51 muL, 0.66 mmol). Diethyl ether (1 mL) was added to precipitate the title compound. 1H NMR (300 MHz, MeOH-D4) delta 1.89-2.04 (m, 1H), 2.05-2.14 (m, 1H), 2.14-2.18 (m, 1H), 2.16 (s, 3H), 2.32-2.46 (m, 1H), 2.64 (td, J=6.5, 3.6 Hz, 1H), 3.33-3.53 (m, 6H), 3.97 (dd, J=13.9, 8.1 Hz, 1H), 5.51-5.58 (m, 1H), 7.32 (d, J=9.4 Hz, 1H), 7.69-7.78 (m, 2H), 7.91-7.98 (m, 2H), 8.11 (d, J=9.3 Hz, 1H) ppm; MS (DCl/NH3): m/z 339 (M+H)+.
79% With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; CyJohnPhos; In 1,4-dioxane; ethanol; water; at 150℃; for 0.166667h;Microwave; The product of Example 9A (182 mg, 0.76 mmol), N-[4-(4,4,5,5-tetramethyl- [1 ,3,2]dioxaborolan-2-yl)-phenyl]-acetamide (Aldrich, 500 mg, 1.9 mmol), dichlorobis(triphenylphosphine)palladium (II) (Aldrich, 53 mg, 0.076 mmol) and 2- (dicyclohexylphosphino)biphenyl (Strem Chemicals, 6.5 mg, 0.019 mmol) were combined with 1 ml_ each of ethanol, p-dioxane, and 1 M aq. sodium carbonate. The mixture was heated in a sealed tube to 150 0C at 330 watts for 10 min in an Emry Creator microwave. The mixture was cooled to room temperature, filtered through Celite, and concentrated onto silica. The product was purified by column chromatography (SiO2, 5% methanol containing 1 % NH4OH -CH2CI2) to provide the title compound (203 mg, 79%).1H NMR (300 MHz, CD3OD) delta 1.96 (m, 1 H), 2.09 (m, 1 H), 2.16 (m, 1 H), 2.16 (s, 3 H), 2.38 (m, 1 H), 2.64 (td, J=6.5, 3.6 Hz, 1 H), 3.33 - EPO <DP n="86"/>3.53 (m, 6 H), 3.97 (dd, J=13.9, 8.1 Hz, 1 H), 5.54 (m, 1 H), 7.32 (d, J=9.4 Hz, 1 H), 7.69 - 7.78 (m, 2 H), 7.91 - 7.98 (m, 2 H), 8.11 (d, J=9.3 Hz, 1 H) ppm; MS (DCI/NH3): m/z 339 (M+H)+.
  • 22
  • 1-(4-bromophenyl)-3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinoline hydrochloride [ No CAS ]
  • [ 214360-60-8 ]
  • N-[4'-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)[1,1'-biphenyl]-4-yl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine)palladium (0); In 1,2-dimethoxyethane; ethanol; water; ethyl acetate; N-[4'-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)[1,1'-biphenyl]-4-yl]acetamide 4'-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)acetanilide (116 mg, 0.444 mmol) and tetrakis(triphenylphosphine)palladium (0) (11 mg, 0.0095 mmol) were added to a suspension of 1-(4-bromophenyl)-3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinoline hydrochloride (181 mg, 0.402 mmol) and sodium carbonate (149 mg, 1.41 mmol) in 1,2-dimethoxyethane (1.2 mL), ethanol (0.6 mL) and water (0.6 mL) and the mixture was stirred at 85 C for 15 hours under nitrogen atmosphere. The reaction mixture was combined with water, and washed twice with ethyl acetate. The combined organic layer was washed with water and brine, and dried through sodium sulfate-basic silica gel (eluding with ethyl acetate) and then concentrated under reduced pressure. The residue was subjected to a column chromatography on a basic silica gel (hexane/ethyl acetate, 2:1 followed by 1:1), and crystallized from ethyl acetate-hexane to obtain the title compound (102 mg, yield: 54%). Melting point: 128-132 C. 1H NMR (CDCl3) delta 1.26 (6H, s), 1.33 (6H, s), 2.21 (3H, s), 2.32 (2H, s), 2.70 (2H, s), 3.93 (3H, s), 6.62 (1H, s), 7.23 (1H, br s), 7.46 (2H, d, J = 8.6 Hz), 7.56-7.64 (4H, m), 7.60 (2H, d, J = 8.6 Hz).
  • 23
  • 1-(3-bromophenyl)-3,4,8,9-tetrahydro-3,3,8,8-tetramethylfuro[2,3-h]isoquinolinol [ No CAS ]
  • [ 214360-60-8 ]
  • N-[3'-(3,4,8,9-Tetrahydro-6-hydroxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)[1,1'-biphenyl]-4-yl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine)palladium (0); In methanol; 1,2-dimethoxyethane; ethanol; water; ethyl acetate; N-[3'-(3,4,8,9-Tetrahydro-6-hydroxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)[1,1'-biphenyl]-4-yl]acetamide A suspension of 1-(3-bromophenyl)-3,4,8,9-tetrahydro-3,3,8,8-tetramethylfuro[2,3-h]isoquinolinol (1.40 g, 3.50 mmol), 4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acetanilide (1.01 g, 3.87 mmol), sodium carbonate (927 mg, 8.75 mmol) and tetrakis(triphenylphosphine)palladium (0) (81 mg, 0.070 mmol) in 1,2-dimethoxyethane (10 mL), ethanol (5 mL) and water (5 mL) was stirred at 80 C for 14 hours under nitrogen atmosphere. The reaction mixture was combined with water, and extractedtwice with ethyl acetate. The combined organic layer was washed with brine, dried through sodium sulfate-basic silica gel (eluding with ethyl acetate followed by ethyl acetate/methanol, 10:1) and concentrated under reduced pressure, and the precipitated powder was recovered by filtration, washed with ethyl acetate-diethyl ether mixture to obtain the title compound (921 mg, yield: 58%). Melting point: 185-189 C. 1H NMR (DMSO-d6) delta 1.14 (6H, s), 1.19 (6H, s), 2.06 (3H, s), 2.23 (2H, s), 2.56 (2H, s), 6.56 (1H, s), 7.29 (1H, d, J = 7.6 Hz), 7.42-7.77 (7H, m), 10.05 (1H, s).
  • 24
  • [ 214360-60-8 ]
  • [ 74-88-4 ]
  • [ 1056456-21-3 ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine; In tetrahydrofuran; at 20℃; for 4h; <strong>[214360-60-8]N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide</strong> (1.0 g, 3.83 mmol), methyl iodide (1.2 eq.) and triethylamine were dissolved in tetrahydrofuran (10 mL), and the reactants were stirred at room temperature for 4 hours. After completion of the reaction was confirmed by TLC, water (50 mL) and ethyl acetate (500 mL) were added to the reactants, followed by extraction. The organic layer was washed with brine and distilled under reduced pressure. The residue was purified by silica gel column chromatography using ethyl acetate and hexane as a developing solvent, thus affording the title compound N-methyl-<strong>[214360-60-8]N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide</strong> (14a). Yield: 80%.MS (ESI+) m/z 276.1 (M+1)
80% With triethylamine; In tetrahydrofuran; at 20℃; for 4h; Preparation Example 19: Preparation of N-methyl-N-(4-(4,4,5,5-tetramethyl-l,3,2- <n="64"/>dioxaborolan-2-yl)phenyI)acetamide (14a)N-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)acetamide (1.0 g, 3.83 mmol), methyl iodide (1.2 eq.) and triethylamine were dissolved in tetrahydrofuran (10 mL), and the reactants were stirred at room temperature for 4 hours. After completion of the reaction was confirmed by TLC, water (50 mL) and ethyl acetate (500 mL) were added to the reactants, followed by extraction. The organic layer was washed with brine and distilled under reduced pressure. The residue was purified by silica gel column chromatography using ethyl acetate and hexane as a developing solvent, thus affording the title compound N-methyl-N-(4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)acetamide (14a). Yield: 80%.MS(ESI+) m/z 276.1 (M+1)
  • 25
  • [ 141-32-2 ]
  • [ 214360-60-8 ]
  • [ 1086400-67-0 ]
  • 26
  • [ 1123302-20-4 ]
  • [ 214360-60-8 ]
  • [ 1123301-87-0 ]
YieldReaction ConditionsOperation in experiment
79% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ISOPROPYLAMIDE; water; at 110℃; for 18h; Dissolve 1 -methyl- lH-pyrazole-4-sulfonic acid (2-[4-(2-chloro-pyridin-3-yl)- piperazin-l-yl]-ethyl}-methyl-amide (230 mg, 0.58 mmol) in DMA-H2O (6 mL; 5: 1 v/v, previously degassed with nitrogen). Add 4'-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)acetanilide (181 mg, 0.69 mmol), potassium carbonate (191 mg, 1.38 mmol) and tetrakis(triphenylphosphine)palladium (33 mg, 0.03 mmol). Heat the reaction mixture at 1100C for 18 hr. Cool and dilute with ethyl acetate and water. Extract the aqueous layer with ethyl acetate and combine the organic layers. Wash the combined organic layers with brine and concentrate. Purify by chromatography, eluting with 1 :2 hexanes: acetone to afford the free base of the title compound (228 mg, 79 % yield) as a white solid.Prepare the dihydrochloride salt by dissolving the free base (182 mg) in acetonitrile and adding IN aqueous HCl (0.962 ml, 0.962 mmol). Stir for 1 hr at ambient <n="48"/>temperature. Remove the organics and lyophilize the remaining aqueous portions to afford the title compound (100% yield). MS ES: m/z = 498 [M+H]+.
  • 27
  • [ 1101173-94-7 ]
  • [ 214360-60-8 ]
  • [ 1198321-20-8 ]
  • 28
  • [ 122-80-5 ]
  • [ 73183-34-3 ]
  • [ 214360-60-8 ]
YieldReaction ConditionsOperation in experiment
93% With tert.-butylnitrite; dibenzoyl peroxide; In acetonitrile; at 20℃; for 1h; Example 6 Synthesis of N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide B2pin2 (1.2 mmol, 305 mg), benzoyl peroxide (0.02 mmol, 5 mg), N-(4-aminophenyl)acetamide (1 mmol, 150 mg) and acetonitrile (3 mL) were added in a 25 mL tube-type reactor, followed by the addition of tert-butyl nitrite (1.5 mmol, 154 mg). The reaction was conducted at room temperature for 1 h. The solution was concentrated after the reaction and the resultant was purified by column chromatography (eluted by petroleum ether:ethyl acetate=20:1, V:V) to give N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide having the following structure: This compound is white solid and obtained in 93% yield. Its NMR data are as follows: 1H NMR (400 MHz, CDCl3) delta 7.76 (d, 1H, J=8.4 Hz), 7.53 (d, 1H, J=8.3 Hz), 2.16(s, 3H), 1.33~1.24(m, 12H); 13C NMR (100 MHz, CDCl3) delta 168.5, 140.5, 135.6, 128.8, 119.9, 118.5, 83.6, 74.9, 24.9, 24.7, 24.5, 24.4.
93% With tert.-butylnitrite; dibenzoyl peroxide; In acetonitrile; at 20℃; for 1h; B2pin2 (1.2 mmol, 305 mg), benzoyl peroxide (0.02 mmol, 5 mg), N-(4-aminophenyl)acetamide (1 mmol, 150 mg) and acetonitrile (3 mL) were added in a 25 mL tube-type reactor, followed by the addition of tert-butyl nitrite (1.5 mmol, 154 mg). The reaction was conducted at room temperature for 1 h. The solution was concentrated after the reaction and the resultant was purified by column chromatography (eluted by petroleum ether : ethyl acetate = 20:1, V:V) to give N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide having the following structure: This compound is white solid and obtained in 93% yield. Its NMR data are as follows: 1H NMR (400MHz, CDCl3) delta 7.76 (d, 1H, J=8.4Hz), 7.53 (d, 1H, J=8.3Hz), 2.16(s, 3H), 1.33~1.24(m, 12H); 13C NMR (100MHz, CDCl3) delta 168.5, 140.5, 135.6, 128.8, 119.9, 118.5, 83.6, 74.9, 24.9, 24.7, 24.5, 24.4.
  • 29
  • ((S)-1-{N'-(4-bromobenzyl)-N'-[(S)-3-hydroxy-3-((1S,2R)-2-hydroxyindan-1-ylcarbamoyl)-4-phenylbutyl]hydrazinocarbonyl}-2,2-dimethylpropyl)carbamic acid methyl ester [ No CAS ]
  • [ 214360-60-8 ]
  • [ 1202901-66-3 ]
  • 30
  • [ 39478-78-9 ]
  • [ 214360-60-8 ]
  • [ 1190222-38-8 ]
YieldReaction ConditionsOperation in experiment
66% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 7h;Reflux; (i) N-(3'-amino-4'-methylbiphenyl-4-yl)acetamido; 0.60 g (3.20 mmol) of 5-bromo-2-methylaniline and 1.01 g (4.87 mmol) of 4-acetamidophenylboronic acid pinacol ester were dissolved in 15 mL of DME. Next, 5 mL of a 2M aqueous sodium carbonate solution, and then 369 mg (0.32 mmol) of tetrakis (triphenyl phosphine)palladium (0) were added and heated under reflux for 7 hours. After completion of the reaction, ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed with a saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. Filtration was then carried out, and the filtrate was condensed. The resulting crude product was separated and purified using silica gel column chromatography to give N-(3'-amino-4'-methylbiphenyl-4-yl)acetamido (yield: 66%). 1H-NMR (CDCl3) delta: 2.19 (3H, s), 2.20 (3H, s), 3.68 (2H, br), 6.88-6.94 (2H, m), 7.10 (1H, d, J = 7.4 Hz), 7.29-7.32 (1H, m), 7.48-7.55 (4H, m).
  • 31
  • [ 1057140-03-0 ]
  • [ 1290639-86-9 ]
  • [ 214360-60-8 ]
  • [Fe(C5H5)(C5H4C6H4C20H8N4H2C6H4NHCOCH3(C6H3(C(CH3)3)2)2)] [ No CAS ]
  • [(Fe(C5H5)(C5H4C6H4))2C20H8N4H2(C6H3(C(CH3)3)2)2] [ No CAS ]
  • 32
  • [ 625-92-3 ]
  • [ 214360-60-8 ]
  • [ 1351665-26-3 ]
  • 33
  • [ 3934-20-1 ]
  • [ 214360-60-8 ]
  • [ 945756-13-8 ]
YieldReaction ConditionsOperation in experiment
97% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; acetonitrile;Reflux; Inert atmosphere; A RBF was charged with 2, 4-dichloropyrimindine (784?mg, 5.2?mmol, 1 equiv.), compound 48 (1.5?g, 5.74?mmol, 1.1 equiv.), Pd(PPh3)4 (250?mg, 0.226?mmol, 0.05 equiv.) and sodium carbonate (991?mg, 9.36?mmol, 1.8 equiv.) MeCN: H2O (9: 1, 40?mL) were added into the RBF and the reaction mixture was degassed under N2, stirred and refluxed overnight under N2. The reaction was cooled, and the reaction mixture was concentrated under vacuum. EA and water were added for extraction. By collecting the organic layer and evaporating solvent, a light yellow crude product was obtained, which was purified using flash chromatography (elution system - EA/Hexane?=?1: 1 to MeOH/EA?=?2: 98) to give 5 a light yellow solid (1.25?g, 97%). Rf?=?0.43 (EA/Hexane?=?1: 1); 1H NMR (400?MHz, DMSO-d6) delta 10.27 (s, 1H), 8.75 (d, J?=?5.4?Hz, 1H), 8.16 (d, J?=?8.9?Hz, 2H), 8.06 (d, J?=?5.4?Hz, 1H), 7.77 (d, J?=?8.9?Hz, 2H), 2.09 (s, 3H); 13C NMR (100?MHz, DMSO-d6) delta 169.33, 166.20, 161.29, 160.98, 143.40, 129.14, 128.72, 119.39, 115.70, 24.64; MS (ESI) 248.0 [M+H]+.
  • 34
  • [ 1193-21-1 ]
  • [ 214360-60-8 ]
  • [ 954219-22-8 ]
YieldReaction ConditionsOperation in experiment
31 mg Compound 104 was prepared by a two-step procedure similar to that of Cai and coworkers22 and Plate and co-workers.23 In the first step, a similar procedure22 to that previously described for 98 was followed, using 4-acetamidophenylboronic acid pinacol ester (91) (0.10 g, 0.38 mmol), 4,6dichloropyrimidine (95) (0.18 g, 1.23 mmol), sodium hydrogen carbonate (97 mg, 1.15 mmol) and bis(triphenylphosphine)palladium(II) chloride (14 mg, 0.02 mmol) in toluene (2 mL), ethanol (1 mL) and water (0.5 mL). The reaction was allowed to cool, diluted with ethyl acetate (50 mL), washed with water (50 mL), the separated aqueous layer further extracted with ethyl acetate (2 × 50 mL), and the combined organic phases dried over anhydrous magnesium sulfate, filtered and the solvent removed in vacuo to afford crude 6-chloro-4-(4'-acetamidophenyl)pyrimidine (101) as a light brown solid (31 mg), which was used without further purification. In the second step, to a stirring solution of crude 6chloro-4-(4'-acetamidophenyl)pyrimidine (101) (31 mg) in tetrahydrofuran (5 mL) and aqueous ammonia (2.20 mL, 32.25 mmol, 15 M) was added zinc powder (0.22 g, 3.31 mmol), and the reaction mixture heated under reflux for 5 h. The solution was filtered through celite and the solvent removed in vacuo. The resulting residue was taken up in ethyl acetate (50 mL), washed with water (50 mL), the separated aqueous layer further extracted with ethyl acetate (2 × 50 mL) and the combined organic phases dried over anhydrous magnesium sulfate, filtered and the solvent removed in vacuo. Purification by flash chromatography (hexane:ethyl acetate 1:1) afforded 104 as a pale brown solid (12 mg, 0.06 mmol, 15% over two steps); Rf = 0.15 (hexane:ethyl acetate, 1:1); mp 206-210 C [ lit.24 mp 213-214 C]; 1H NMR (400MHz; CDCl3) deltaH 2.19 (3H, s, CH3), 7.72-7.74 (3H, m, H-3', H-5', H-5), 8.05 (2H, d, J = 8.4 Hz, H-2', H-6'), 8.71 (1H, dd, J = 5.2 Hz, J = 1.2 Hz, H-6) and 9.18 (1H, s, H-2); 13C NMR (100MHz, CDCl3) deltaC 23.9 (CH3), 116.7 (CH), 119.6 (CH), 127.9 (CH), 131.1 (C), 141.4 (C), 156.9 (CH), 158.4 (CH), 163.6 (C) and 169.8 (C).
  • 35
  • [ 13382-54-2 ]
  • [ 214360-60-8 ]
  • [ 1351665-21-8 ]
 

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