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Chemical Structure| 22237-13-4 Chemical Structure| 22237-13-4

Structure of 22237-13-4

Chemical Structure| 22237-13-4

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Product Details of [ 22237-13-4 ]

CAS No. :22237-13-4
Formula : C8H11BO3
M.W : 165.98
SMILES Code : OB(C1=CC=C(OCC)C=C1)O
MDL No. :MFCD00674028
InChI Key :WRQNDLDUNQMTCL-UHFFFAOYSA-N
Pubchem ID :2734351

Safety of [ 22237-13-4 ]

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

Computational Chemistry of [ 22237-13-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 47.57
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

1.16
Log Po/w (WLOGP)?

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

-0.23
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.

0.33
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

-0.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.16

Water Solubility

Log S (ESOL):?

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

-1.77
Solubility 2.81 mg/ml ; 0.0169 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.

-1.8
Solubility 2.64 mg/ml ; 0.0159 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

-1.81
Solubility 2.56 mg/ml ; 0.0154 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.

-6.49 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)

1.69

Application In Synthesis of [ 22237-13-4 ]

* 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 [ 22237-13-4 ]

[ 22237-13-4 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 22237-13-4 ]
  • [ 55329-22-1 ]
  • rac-2-hydroxy-3,3-diphenyl-butyric acid cesium salt [ No CAS ]
  • 2-[4-(4-ethoxy-phenyl)-6-methyl-pyrimidin-2-yloxy]-3,3-diphenyl-butyric acid [ No CAS ]
  • 2
  • [ 22237-13-4 ]
  • [ 586-78-7 ]
  • [ 109662-72-8 ]
YieldReaction ConditionsOperation in experiment
91% With dichloro bis(acetonitrile) palladium(II); C95H120N20O10(10+)*10F6P(1-); potassium carbonate; In ethanol; at 50℃; for 1.5h; General procedure: In a typical run, a mixture of aryl bromide (0.50 mmol),phenylboronic acid (0.55 mmol), K2CO3 (1.5 mmol),0.2 mol% ligand, 1 mol% PdCl2(CH3CN)2 in 1.5 mL of ethanol were stirred at 50 C for 1.5 h under air. Solvent ethanol was removed completely under vacuum degree0.09 MPa at 45 C to give a crude product. The pure product was isolated by column chromatography on silica.
  • 3
  • [ 42872-74-2 ]
  • [ 22237-13-4 ]
  • 4'-ethoxy-6-methyl-biphenyl-3-carbonitrile [ No CAS ]
  • 4
  • [ 684284-68-2 ]
  • [ 22237-13-4 ]
  • [ 684287-25-0 ]
YieldReaction ConditionsOperation in experiment
21% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 120℃; for 6h; To a solution of trifluoro-methanesulfonic acid 9-benzhydryloxy-7-(4-fluoro- benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo [3,4-g]quinolin-5-yl ester 46 (40 mg, 0.064 mmol) dissolved in toluene (3 mL)/ ethanol (0.6 mL)/ water (0.4 mL) was added K2C03 (27 mg, 0.192 mmol), 4-ethoxyphenolboronic acid (22 mg, 0.128 mmol) and tetrakis-(triphenylphosphine)-palladium(0) (15 mg, 0.013mmol). The reaction mixture in the flask was flashed with argon three times. It was then heated to 120C under argon 3 hours. The reaction was monitored by TLC (EtOAc/hexane 3/7) (Rf46 = 0.6, Rf275 = 0.4) and LC/MS. After cooling to room temperature, the mixture was diluted with EtOAc (20mL) and washed with IN HCl, saturated NaHC03 and brine. The organic phase was dried (MgS04), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography ( ethylacetate/hexane - 1/3) to afford 9- benzhydryloxy-5-(4-ethoxy-phenyl)-7-(4-fluoro-benzyl)-6,7-dihydro-pyrrolo[3,4- g] quinolin-8-one 275 (8.0 mg, 21%) as a solid: ¹H NMR (CDC13) No. 9.0 (d, 1H), 8.1 (s, 1H), 7.9 (d, 1H), 7.8-7.5 (dd, 4H), 7.5 (s, 1H), 7.4 (dd, 2H), 7.3-7.1 (m, 10H), 7.0 (t, 2H), 4.8 (s, 2H), 4.1 (m, 2H), 4.0 (s, 1H), 1.4 (t, 3H) ; MS: 595 (M+1).
  • 5
  • [ 701270-84-0 ]
  • [ 22237-13-4 ]
  • [ 701270-97-5 ]
YieldReaction ConditionsOperation in experiment
44% With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; water; at 55℃; for 3h; TERT-BUTYL-4-[(2-BROMO-1, 3-benzothiazol-6-yl) sulfonyl] tetrahydro-2H-pyran-4-carboxylate (1.0 g; MW 465.63 ; prepared in accordance with Part C, Example 9), 4-ETHOXY BORONIC acid (from Aldrich, 0.43 g, MW 165.98, 1.2 eq), (1, L'BIS- (DIPHENYLPHOSPHINO)-FERROCENE) palladium dichloride (from Aldrich, 0.09 g, MW 816.64, 0.05 eq), and 2 M sodium carbonate (aqueous, 3.3 ml, 3.0 eq) were slurried in ethylene glycol dimethylether (15 ML). The resulting mixture was heated at 55C for 3 hr. Afterward, the mixture was cooled to room temperature and then filtered through a Celite plug. The filtrate was diluted with water (20 ml). The diluted mixture was extracted with ethyl acetate (3x25 ml). The organics were combined and then washed with water (2x30 ml), washed with brine (1x30 ml), dried over sodium sulfate, filtered, and concentrated to form a black oily solid. Recrystallization from methanol afforded the desired ester as a white solid (0.45 g, 44% YIELD). 1H NMR and LCMS confirmed the presence of the desired ester. The "equivalents"above indicate equivalents relative to the charged amount of tert-butyl- carboxylate.
  • 6
  • [ 22237-13-4 ]
  • argon [ No CAS ]
  • [ 1122-91-4 ]
  • [ 224311-51-7 ]
  • 4'-ethoxybiphenyl-4-carbaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
203 mg (90%) With potassium fluoride;palladium diacetate; In tetrahydrofuran; EXAMPLE 33 Synthesis of 4-formyl-4'-ethoxybiphenyl An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (1.1 mg, 0.005 mmol, 0.5 mol %), 2-(di-tert-butylphosphino)biphenyl (3.0 mg, 0.01 mmol, 1.0 mol %), 4-ethoxyphenylboronic acid (249 mg, 1.5 mmol), potassium fluoride (174 mg, 3.0 mmol), and 4-bromobenzaldehyde (185 mg, 1.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) was added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl bromide had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 203 mg (90%) of the title compound.
203 mg (90%) With potassium fluoride;palladium diacetate; In tetrahydrofuran; Example 33 Synthesis of 4-formyl-4'-ethoxybiphenyl An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (1.1 mg, 0.005 mmol, 0.5 mol %), 2-(di-tert-butylphosphino)biphenyl (3.0 mg, 0.01 mmol, 1.0 mol %), 4-ethoxyphenylboronic acid (249 mg, 1.5 mmol), potassium fluoride (174 mg, 3.0 mmol), and 4-bromobenzaldehyde (185 mg, 1.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) was added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl bromide had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 203 mg (90%) of the title compound.
  • 7
  • [ 934018-46-9 ]
  • [ 22237-13-4 ]
  • 7-(4-ethoxyphenyl)-2-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-3H-imidazo[4,5-b]pyridine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% Example 357-(4-Ethoxyphenyl)-2-{4-[(4-methylpiperazin-l-yl)carbonyl]phenyl}-3JHr-imidazo[4,5- 6]pyridine hydrochlorideA mixture of the 7-chloro-2- {4-[(4-methylpiperazin- 1 -yl)carbonyl]phenyl} -3H- imidazo[4,5-6]pyridine (0.20 g, 0.56 mmol, obtained from Example 5(d)), (4- ethoxyphenyl)boronic acid (0.19 g, 1.12 mmol), PdCl2(dppf)*DCM (0.023 g, 0.028 mmol) and sodium carbonate (0.33 g, 3.09 mmol) in 2 mL TηF/water (9:1) were heated in a microwave reactor at +160 C for 10 minutes. After cooling to room temperature the mixture was diluted with EtOAc and washed with water. The organic phase was dried(MgSO4), filtered and evaporated in vacuo. The residue was purified by preparative ηPLC, which afforded the product as a base. The base was dissolved in TKF and hydrochloric acid (IM HCl in diethyl ether) was added until precipitation formed. The solvent was evaporated in vacuo affording the title compound 0.078 g (29%). 1H NMR (DMSO-J6) δ ppm 13.73 (br s, 1 H), 8.53 - 8.23 (m, 5 H), 7.66 - 7.45 (m, 3 H), 7.24 - 7.03 (m, 2 H), 4.14 (q, 2 H), 3.75 - 3.55 (m, 2 H), 3.48 - 3.33 (m, 2 H), 2.45 - 2.24 (m, 4 H), 2.21 (s, 3 H), 1.38 (t, 3 H); MS (ESI) m/z 441 (M+l).
  • 8
  • [ 942411-17-8 ]
  • [ 22237-13-4 ]
  • (RS)-N-(ethoxycarbonyl)-S-(3-[4-{methyl-sulfanyl}-5-(4-ethoxy-phenyl)-pyrimidin-2-yl]amino}phenyl)-S-methylsulfoximide [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); trifuran-2-yl-phosphane; In 1,2-dimethoxyethane; water; at 80℃; for 20h; b) (RS)-N-(Ethoxycarbonyl)-S-(3-[4-{methyl-sulfanyl}-5-(4-ethoxy-phenyl)- pyrimidin-2-yl]amino}phenyl)-S-methylsulfoximide:; <n="245"/>(f?S)-λ/-(Ethoxycarbonyl)-S-(3-[5-bromo-4-(methylsulfanyl)pyrimindin-2- yl]amino}phenyl)-S-methylsulfoximide (0.90 g (2.0 mmol), 4- ethoxyphenylboronic acid (0.35 g, 2.1 mmol), tri(2-furyl)phosphine (200 mg, 0.80 mmol), and 20 ml. of dry DME are mixed in 50-mL flask and purged with argon. Then, aqueous 1 M NaCU3 (3.2 mL) is added, the flask is purged with argon again and then Pd(PPh3)4 (100 mg, 0.10 mmol) is added and the mixture is stirred under argon at 80 0C for 20 h. Subsequently, the mixture is poured into aqueous NaHCO3 (200 mL), extracted with DCM, dried (Na2SO4) and evaporated. The product is isolated by HPLC to give the desired compound (650 mg, 66 % yield). Larger batches can be readily crystallised from acetonitrile. 1H-NMR (300 MHz, DMSO): 10.15 (s, 1 H); 8.72 (s, 1 H); 8.11 (s, 1 H); 7.80 - 8.02 (m, 1 H); 7.42 - 7.67 (m, 2 H); 7.34 (d, 2 H); 7.01 (d, 1 H); 3.82 - 4.16 (m, 4 H); 3.38 (s, 3 H); 2.56 (s, 3 H); 1.20 - 1.44 (m, 3 H); 0.99 - 1.14 (m, 3 H).MS (ESI): [M+Hf = 487.
66% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); trifuran-2-yl-phosphane; In 1,2-dimethoxyethane; water; at 80℃; for 20h; (RS)-N-(Ethoxycarbonyl)-S-(3-[5-bromo-4-(methylsulfanyl)pyrimindin-2-yl]amino}phenyl)-S-methylsulfoximide (0.90 g (2.0 mmol), 4-ethoxyphenylboronic acid (0.35 g, 2.1 mmol), tri(2-furyl)phosphine (200 mg, 0.80 mmol), and 20 mL of dry DME are mixed in 50-mL flask and purged with argon. Then, aqueous 1 M NaCO3 (3.2 mL) is added, the flask is purged with argon again and then Pd(PPh3)4 (100 mg, 0.10 mmol) is added and the mixture is stirred under argon at 80 C. for 20 h. Subsequently, the mixture is poured into aqueous NaHCO3 (200 mL), extracted with DCM, dried (Na2SO4) and evaporated. The product is isolated by HPLC to give the desired compound (650 mg, 66% yield). Larger batches can be readily crystallised from acetonitrile. 1H-NMR (300 MHz, DMSO): 10.15 (s, 1 H); 8.72 (s, 1 H); 8.11 (s, 1 H); 7.80-8.02 (m, 1 H); 7.42-7.67 (m, 2 H); 7.34 (d, 2 H); 7.01 (d, 1 H); 3.82 -4.16 (m, 4 H); 3.38 (s, 3 H); 2.56 (s, 3 H); 1.20-1.44 (m, 3 H); 0.99-1.14 (m, 3 H). MS (ESI): [M+H]+=487.
  • 9
  • [ 1028727-36-7 ]
  • [ 22237-13-4 ]
  • [ 1028727-46-9 ]
YieldReaction ConditionsOperation in experiment
70% With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 90℃; for 12h; To a solution of 4' - [ (5-bromo-2-butyl-4-cyclopropyl-6- oxopyrimidin-1 (6H) -yl) methyl] biphenyl-2-carbonitrile (0.5 g) and 4-ethoxyphenylboronic acid (0.27 g) in 1,4-dioxane (10 mL) were added 2 M aqueous cesium carbonate solution (2 mL) and [1,1' -bis (diphenylphosphino) ferrocene] dichloropalladium (0.05 g) , and the mixture was stirred at 900C for 12 hr under an argon atmosphere. The reaction mixture was diluted with ethyl acetate, and the insoluble material was filtered off through celite. The filtrate was washed successively with 1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound (0.38 g, 70%) as a colorless solid. 1H NMR (300 MHz, CDCl3) δ 0.76-0.87 (2H, m) , 0.91 (3H, t, J = 7.5), 1.10-1.20 (2H, m) , 1.31-1.47 (5H, m) , 1.61-1.75 (2H, m) , 1.83-1.96 (IH, m) , 2.67 (2H, t, J = 7.5), 4.06 (2H,_ q, J = 7.5), 5.35 (2H, s) , 6.96 (2H, d, J = 8.1), 7.31-7.56 (8H, m) , 7.60-7.69 (IH, m) , 7.76 (IH, d, J = 7.5)
  • 10
  • [ 1061743-41-6 ]
  • [ 22237-13-4 ]
  • [ 1061743-42-7 ]
YieldReaction ConditionsOperation in experiment
88% With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 85℃; for 2h; Preparation of compound (50); A mixture of ester (45) (200 mg, 0.34 mmol), 4-ethoxyphenylboronic acid (96 mg, 0.58 mmol), Pd(PPh3)4 (20 mg, 0.017 mmol) and K3PO4 (166 mg, 0.78 mmol) in 4.5 mL dioxane/H2O 5:1 was heated to 85C under nitrogen. After 2h, the reaction mixture was diluted with sat. solution of NaHC03, extracted with ACOEt and dried over Na2SO4. The organic layer was concentrated in vacuo and the crude product was purified by flash chromatography on silica gel (n-hexane/AcOEt = 4:1) to give (50) (193 mg, 88 % yield). 1H-NMR (CDCl3) δ: 1.20-1.39 (m, 15H); 1.45 (t, J= 6.9Hz, 3H); 2.04-2.35 (m, 2H); 3.50-3.80 (m, 2H); 4.05-4.15 (m, 3H); 4.46 (septet, J= 6.2Hz, 1H); 6.97-7.01 (m, 2H); 7.51-7.88 (m, 10H).
  • 11
  • [ 1050393-12-8 ]
  • [ 22237-13-4 ]
  • [ 1050393-15-1 ]
YieldReaction ConditionsOperation in experiment
53.5% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; toluene; at 60℃; Alternative Preparation VI-3, Q = 4-Ethoxyphenyl:; Degas a solution of (R,R)-N-[3,4-dibromoisothiazol-5-yl]-2-methylcyclopropane- carboxamide (0.500 g, 1.471 mmol), <strong>[22237-13-4](4-ethoxyphenyl)boronic acid</strong> (0.485 g, 2.941 mmol), DMF (3 mL) and toluene (29 mL) with nitrogen. Add sodium carbonate (2 M) (4.41 mmol) and Pd(PPh3)4 (0.255 g, 0.221 mmol); then seal under nitrogen. Heat at 60 0C overnight. Add 100 mg of Pd(PPh3)4 and heat for 1 more day. Dilute with EtOAc and wash with brine. Separate and evaporate. Chromatography on silica gel, eluting with 15- 50% EtOAc in hexane, followed by crystallization from EtOAc and hexane affords (R,R)-N-[4-bromo-3-(4-ethoxyphenyl)isothiazol-5-yl]-2-methylcyclopropane- carboxamide. Yield: 53.5% ES-MS: 380.0 (m+1).
  • 12
  • C24H27BrN2O8S [ No CAS ]
  • [ 22237-13-4 ]
  • C32H36N2O9S [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 85℃; for 2h;Inert atmosphere of nitrogen; A mixture of ester (45) (200 mg, 0.34 mmol), 4-ethoxyphenylboronic acid (96 mg, 0.58 mmol), Pd(PPh3)4 (20 mg, 0.017 mmol) and K3PO4 (166 mg, 0.78 mmol) in 4.5 mL dioxane/H2O 5:1 was heated to 85C under nitrogen. After 2h, the reaction mixture was diluted with sat. solution of NaHCO3, extracted with ACOEt and dried over Na2SO4. The organic layer was concentrated in vacuo and the crude product was purified by flash chromatography on silica gel (n-hexane/AcOEt = 4:1) to give (50) (193 mg, 88 % yield). 1H-NMR (CDCl3) δ: 1.20-1.39 (m, 15H); 1.45 (t, J= 6.9Hz, 3H); 2.04-2.35 (m, 2H); 3.50-3.80 (m, 2H); 4.05-4.15 (m, 3H); 4.46 (septet, J= 6.2Hz, 1H); 6.97-7.01 (m, 2H); 7.51-7.88 (m, 10H).
  • 13
  • [ 1435-52-5 ]
  • [ 22237-13-4 ]
  • [ 1228186-72-8 ]
YieldReaction ConditionsOperation in experiment
65% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; at 90℃; for 8h;Inert atmosphere; General procedure: 6.3 1,4-Di(4'-ethoxyphenyl)-2-fluorobenzene (7c): Starting with 6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg, 0.50 mmol), Pd(PPh3)4 (3 mol%), 4-ethoxyphenylboronic acid (64 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 7c was isolated as a colorless solid (86 mg, 65%). Mp 96-98 C. 1H NMR (300 MHz, CDCl3): δ = 1.39 (t, J = 7.2 Hz, 6H, CH3), 3.99 (q, J = 6.89 Hz, 4H, OCH2), 6.85-6.91 (m, 4H, CH), 7.21-7.28 (m, 3H, CH), 7.36-7.50 (m, 4H, CH). 13C NMR (75 MHz, CDCl3): δ = 14.9 (2CH3), 63.6 (2OCH2), 106.8 (d, J = 22.0 Hz, C), 114.5 (d, J = 16.5 Hz, CH), 114.7 (CH), 115.0 (CH), 123.4 (d, J = 3.8 Hz, CH), 127.7 (CH), 128.0 (CH), 131.3 (C), 133.6 (CH), 133.9 (C), 144.1 (C), 159.2 (d, 1JCF = 247.0 Hz, C). 19F NMR (282 MHz, CDCl3): δ = -114.92. IR (ATR, cm-1): , 2935 (w), 2838 (w), 1897 (w), 1597 (m), 1474 (s), 1243 (s), 1180 (m), 1027 (s), 805 (s), 751 (m), 692 (m), 412 (w). GC-MS (EI, 70 eV): m/z (%) = 336 (100) [M]+, 307 (22), 280 (32), 279 (15), 251 (14). HRMS (EI) calcd. for C22H21FO2 [M]+: 336.15201; found 336.15196.
  • 14
  • [ 1435-52-5 ]
  • [ 22237-13-4 ]
  • [ 1228186-78-4 ]
YieldReaction ConditionsOperation in experiment
68% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; at 90℃;Inert atmosphere; General procedure: 6.17 1-Bromo-4(4'-ethoxyphenyl)-2-fluorbenzene (8c): Starting with 6 (100 mg, 0.39 mmol), Cs2CO3 (190 mg, 0.50 mmol), Pd(PPh3)4 (3 mol%), 4-ethoxyphenylboronic acid (64.7 mg, 0.39 mmol) and 1,4-dioxane (4 mL), 8c was isolated as a colorless solid (79 mg, 68%). Mp 76-78 C. 1H NMR (300 MHz, CDCl3): δ = 1.37 (t, J = 7.2 Hz, 3H, CH3), 3.99 (q, J = 6.9 Hz, 2H, OCH2), 6.85-6.91 (m, 2H, CH), 7.21-7.28 (m, 3H, CH), 7.36-7.50 (m, 2H, CH). 13C NMR (75 MHz, CDCl3): δ = 14.9 (CH3), 63.6 (OCH2), 106.8 (d, J = 22.0 Hz, C), 114.5 (d, J = 16.5 Hz, CH), 114.7 (CH), 115.0 (CH), 123.4 (d, J = 3.8 Hz, CH), 127.7 (CH), 128.0 (CH), 131.3 (C), 133.6 (CH), 133.9 (C), 144.1 (C), 159.2 (d, 1JCF = 247.0 Hz, C). 19F NMR (282 MHz, CDCl3): δ = -114.92. IR (ATR, cm-1): , 2935 (w), 2838 (w), 1897 (w), 1597 (m), 1474 (s), 1243 (s), 1180(m), 1027 (s), 805 (s), 751 (m), 692 (m), 412 (w). GC-MS (EI, 70 eV): m/z (%) = 294 (78) [M]+, 268 (100), 239 (22), 211 (20), 157 (32), 133 (12), 106 (10). HRMS (EI) calcd. for C14H12BrFO [M]+: 294.00556; found 294.00513.
  • 15
  • [ 22237-13-4 ]
  • [ 139215-43-3 ]
  • [ 1232345-09-3 ]
YieldReaction ConditionsOperation in experiment
65% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; at 90℃; for 8h;Inert atmosphere; General procedure: 4.15 2-Bromo-3,5-difluoro-4'-ethoxybiphenyl (4d): Starting with 1 (100 mg, 0.37 mmol), Cs2CO3 (119 mg, 0.37 mmol), Pd(PPh3)4 (3 mol%), 4-ethoxyphenylboronic acid (61 mg, 0.37 mmol), and 1,4-dioxane (4 mL), 4d was isolated as a colorless solid (74 mg, 65%). Mp 111-113 C. 1H NMR (300 MHz, CDCl3): δ = 1.44 (t, J = 6.95 Hz, 3H, CH3), 4.07 (q, J = 6.95, 3H, OCH3), 3.55 (s, 3H, OCH3), 6.83-6.97 (m, 3H, ArH), 7.28-7.34 (m, 3H, ArH). 13C NMR (62.89 MHz, CDCl3): δ = 14.8 (CH3), 63.5 (OCH2), 103.2 (t, J = 27.0 Hz, CH), 113.5 (d, J = 4.0 Hz, CH), 113.7 (dd, J = 22.2, 3.4 Hz, C), 114.1 (2CH), 128.4 (d, J = 6.9 Hz, CH), 128.7 (CH), 130.4 (CH), 133.7 (CH), 141.3 (d, J = 9.4 Hz, C), 159.0 (C), 159.3 (dd, JCF = 247.9, 13.3 Hz, CF), 161.3 (dd, JCF = 249.5, 13.3 Hz, CF). 19F NMR (282.4 MHz, CDCl3): δ = -101.8 (CF), -112.5 (CF). IR (ATR): , 2956 (w), 2926 (w), 2835 (w), 1616 (w), 1596 (w), 1503 (w), 1494 (w), 1455 (w), 1421 (w), 1338 (w), 1287 (w), 1247 (m), 1201 (w), 1180 (w), 1120 (w), 1089 (w), 1024 (m), 928 (w), 877 (w), 865 (w), 800 (w), 755 (w), 744 (m), 701 (w), 635 (w), 586 (m), 537 (w) cm-1. MS (EI, 70 eV): m/z (%) = 312 (61) (79Br) [M]+, 287 (12), 286 (98), 284 (100), 204(10). HRMS (EI) calcd. for C14H11O81BrF2 [M]+: 313.99354; found 313.99349.
  • 16
  • [ 22237-13-4 ]
  • [ 139215-43-3 ]
  • [ 1232345-03-7 ]
YieldReaction ConditionsOperation in experiment
68% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; at 90℃; for 8h;Inert atmosphere; General procedure: 4.7 1,2-Di(4'-ethoxyphenyl)-3,5-difluorobenzene(3e): Starting with 1 (100 mg, 0.37 mmol), Cs2CO3 (263 mg, 0.81 mmol), Pd(PPh3)4 (3 mol%), 4-ethoxyphenylboronic acid (135 mg, 0.81 mmol), and 1,4-dioxane (4 mL) 3e was isolated as a colorless solid (88 mg, 68%). Mp 69-71 C. 1H NMR (300 MHz, CDCl3): δ = 1.36-1.43 (m, 4H, CH2), 3.94-4.03 (m, 6H, OCH3), 6.69-7.01 (m, 10H, ArH). 13C NMR (62.89 MHz, CDCl3): δ = 14.8 (CH3), 14.9 (CH3), 63.2 (OCH2), 63.3 (OCH2), 102.3 (t, J = 26.5 Hz, CH), 112 (dd, J = 21.8, 3.6 Hz, CH), 113.9 (2CH), 114.0 (2CH), 114.7 (2CH), 125.6 (C), 127.7 (C), 130.7 (2CH), 131.0 (C), 132.2 (C), 157.9 (C), 158.1 (C), 160.0 (dd, JCF = 249.2, 12.6 Hz, CF), 161.1 (dd, JCF = 249.2, 13.3 Hz, CF). 19F NMR (282.4 MHz, CDCl3): δ = -110.09 (CF), -112.02 (CF). IR (ATR, cm-1): , 3036 (w), 2975 (w), 2929 (w), 2873 (w), 1730 (w), 1605 (m), 1586 (m), 1511 (m), 1460 (m), 1432 (m), 1393 (m), 1335 (w), 1285 (m), 1239 (s), 1177 (m), 1110 (m), 1046 (m), 997 (m), 934 (w), 867 (m), 819 (s), 758 (m), 647 (w), 616 (m), 594 (w), 559 (m), 536 (m). MS (EI, 70 eV): m/z (%) = 354 (100) [M]+, 326 (21), 298 (30), 297 (22), 251 (24). HRMS (EI) calcd. for C22H20O2F2 [M]+: 354.14259; found 354.14230.
  • 17
  • [ 22237-13-4 ]
  • [ 99-90-1 ]
  • [ 56116-83-7 ]
YieldReaction ConditionsOperation in experiment
85.6% With palladium diacetate; sodium carbonate; triphenylphosphine; In propan-1-ol; water; at 100℃; for 1h; {0277] Briefly, to a solution of 4-bromoacetophenone, 10.28 g (51.64 mmol), 4- ethoxyphenylboronic acid, 7.80g (4.70 mmol) in 1-propanol (120 mL), palladium acetate, 48.94 mg, triphenylphosphine, 164.83 mg, sodium carbonate solution (aq. 2 M, 35 mL), and then water (25 mL) were added. The reaction mixture was stirred in 100 C oil bath for 1 hour, cooled to room temperature, and then the reaction flask was placed in ice bath for 2 hours. The white crystals were collected by filtration, washed with cooled water and then allowed to dry under ambient temperature and pressure. Product yield 9.67 g (85.6%).
  • 18
  • [ 22237-13-4 ]
  • [ 6630-33-7 ]
  • [ 1183939-73-2 ]
YieldReaction ConditionsOperation in experiment
82.6% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 6h; Example 4Synthesis of N-[(E)-3-(4'-ethoxy-biphenyl-2-yl)-2-methyl-acryloyl]-guanidine<Step 1>2-bromobenzaldehyde (200 mg, 1.08 mmol) and 4-ethoxyphenylboronic acid (179 mg, 1.08 mmol) were dissolved in a mixed solution of dioxane and water (v/v=3/1, 8 mL). Pd(PPh3)4 (125 mg, 0.108 mmol) and Na2CO3 (343 mg, 3.24 mmol) were added to the solution and then stirred at 90 C. for 6 hours. After cooling it to room temperature, EtOAc was added thereto, washed with NaHCO3 solution, water and saturate saline and then dried over anhydrous MgSO4. The solvent was eliminated in vacuo and then purified by silica gel column chromatography (Hexane/EtOAc) to obtain the objective aldehyde (202 mg, 82.6%).1H-NMR (d-DMSO, 300 MHz) ς 1.46 (t, 3H, J=7.0 Hz), 4.10 (q, 2H, J=7.0 Hz), 6.99 (d, 2H, J=8.5 Hz), 7.26 (s, 1H), 7.30 (d, 2H, J=8.5 Hz). 7.39-7.50 (m, 2H), 7.62 (ddd, 2H, J=1.5, 7.3, 7.3 Hz), 7.39-7.50 (m, 2H, J=1.1, 7.3 Hz), 10.0 (s, 1H)MS: 227
  • 19
  • C42H37ClF6N4O20S2 [ No CAS ]
  • [ 22237-13-4 ]
  • C56H55ClN4O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 32℃; for 5h;Inert atmosphere; (b) Compound 51; Tetrakis(triphenylphosphine)palladium(0) (682 mg) was added to triflate 50 (11 g), 4- ethoxybenzeneboronic acid (4.24 g) and sodium carbonate (5.4 g) in a mixture of toluene (220 mL), ethanol (110 mL) and water (110 mL). The reaction mixture was allowed to stir for 5 hours under an argon atmosphere at 32C. During this time the product was observed to precipitate from the reaction mixture. The reaction mixture was diluted with ethyl acetate and washed with water, brine and dried over magnesium sulphate. After filtration excess ethyl acetate was removed by rotary evaporation under reduced pressure. The crude coupling product was purified by flash column chromatography (silica gel; gradient 50/50 ethyl acetate/hexane to 70/30 ethyl acetate/hexane). Pure fractions were combined and removal of excess eluent afforded the pure product 51 as an orange solid (8.6 g, 82 % yield, LC/MS 3.72 mins, m/z ES+ 1063.25).
  • 20
  • [ 1220904-29-9 ]
  • [ 22237-13-4 ]
  • [ 1220904-32-4 ]
YieldReaction ConditionsOperation in experiment
40% With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 70℃; for 3h; Step 1; The product from Scheme AAE, Step 6 (200 mg, 0.324 mmol, 1 eq), 4- ethoxyphenylboronic acid (81 mg, 0.49 mmol, 1.5 eq), andbis(triphenylphosphino)palladium(ll)chioride (10 mg, 0.02 mmol, 0.05 eq) were combined with 2 Na2C03 (aq.) (1 -5 ml_) and DME (3 mL) in a scintillation vial. The reaction was heated in a heating block at 70C for 3h. The reaction was cooled and was partitioned between EtOAc and water. The organic layer was removed and saved, and the aqueous layer was extracted with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filitered, and evaporated to afford a crude product which was purified via silica gel chromatography (gradient eiution, 0% to 100% EtOAc in hexanes, SiO2) to afford the desired product (77 mg, 40%).
  • 21
  • [ 1256240-27-3 ]
  • [ 22237-13-4 ]
  • [ 1256265-86-7 ]
YieldReaction ConditionsOperation in experiment
57% With sodium carbonate; lithium chloride;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 75℃; for 15h;Inert atmosphere; Under an inert atmosphere, 0.14 g (0.37 mmol) of tert-butyl (3aR,5s,6aS)-5-(3-bromophenoxy)hexahydrocyclopenta[c]-pyrrole-2(1H)-carboxylate, obtained in step 11.1., 0.08 g (0.51 mmol) of 4-ethoxyphenylboronic acid and 0.04 g (1.04 mmol) of lithium chloride are placed in 3.6 mL of a 1/1/0.4 mixture of ethanol, toluene and water. 0.46 mL (0.92 mmol) of aqueous 2M sodium carbonate solution and 0.02 g (0.02 mmol) of Pd(PPh3)4 are added to the medium. After heating for 15 hours at 75 C., the medium is allowed to cool to room temperature, and then taken up in ethyl acetate and water. The aqueous phase is extracted twice with ethyl acetate and then the combined organic phases are washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue obtained is purified by chromatography on silica gel, eluting with a 95 /5 and then 90/10 mixture of cyclohexane and ethyl acetate. 0.088 g (57%) of expected product is thus obtained in the form of a wax.
  • 22
  • [ 1256240-27-3 ]
  • [ 22237-13-4 ]
  • [ 1256240-28-4 ]
YieldReaction ConditionsOperation in experiment
77% With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; water; at 75℃; for 15h;Inert atmosphere; Under an inert atmosphere, 0.170 g (0.44 mmol) of tert-butyl (3aR,5s,6aS)-5-(3-bromophenoxy)hexahydrocyclopenta[c]-pyrrole-2(1H)-carboxylate, obtained in step 1.1., 0.088 g (0.53 mmol) of 4-ethoxyphenylboronic acid and 0.434 g (1.33 mmol) of caesium carbonate are introduced into 5 ml of a 9/1 mixture of tetrahydrofuran and water. 0.036 g (0.04 mmol) of PdCl2dppf.CH2Cl2 is added and the medium is heated at 75 C. for 15 hours. The medium is allowed to cool to room temperature and then diluted with ethyl acetate and water. The organic phase is separated out and extracted twice with ethyl acetate, and the combined organic phases are washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. After evaporating off the solvent, the residue is purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate. 0.145 g (77%) of expected product is obtained in the form of an oil.
  • 23
  • [ 1415638-43-5 ]
  • [ 22237-13-4 ]
  • [ 1415638-50-4 ]
YieldReaction ConditionsOperation in experiment
72% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride; In 1,4-dioxane; water; at 45 - 65℃; for 5.5h;Inert atmosphere; General procedure: A stirred suspension of 5-bromo-4-(3,4,5-trimethoxyphenyl)-thiazole derivative 7a or 7c (0.5 mmol) and the appropriate phenylboronic acid (1 mmol) in dioxane (6 mL containing 3 drops of water) was degassed under a stream of nitrogen for 10 min, then treated with [1,10-bis(diphenylphosphino)ferrocene] dichloropalladium (II) methylene chloride complex (41 mg, 0.05 mmol) and cesium fluoride (190 mg, 1.25 mmol). The reaction mixture was heated under nitrogen at 45 C for 30 min, then at 65 C for 5 h. The reaction mixture was cooled to ambient temperature, diluted with CH2Cl2 (10 mL), filtered through a pad of celite and evaporated in vacuo. The residue was dissolved with CH2Cl2 (15 mL), and the resultant solution was washed sequentially with water (5 mL) and brine (5 mL). The organic layer was dried and evaporated, and the residue was purified by flash chromatography on silica gel.
  • 24
  • [ 1415638-44-6 ]
  • [ 22237-13-4 ]
  • [ 1415638-34-4 ]
YieldReaction ConditionsOperation in experiment
73% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride; In toluene; at 55 - 75℃; for 20.75h;Inert atmosphere; General procedure: To a stirred suspension of 7b (0.5 mmol) and the appropriate phenylboronic acid (1 mmol) in toluene (7 mL) was added [1,10-bis(diphenylphosphino)ferrocene]dichloropalladium (II) methylene chloride complex (41 mg, 0.05 mmol) and cesium fluoride (190 mg, 1.25 mmol). The reaction mixture was heated under nitrogen at 55 C for 45 min, then at 75 C for 20 h. The reaction mixture was cooled to ambient temperature, diluted with CH2Cl2 (10 mL), filtered through a pad of celite and evaporated in vacuo. The residue was dissolved with CH2Cl2 (15 mL), and the resultant solution was washed sequentially with water (5 mL) and brine (5 mL). The organic layer was dried and evaporated, and the residue was purified by flash chromatography on silica gel
  • 25
  • [ 1415638-45-7 ]
  • [ 22237-13-4 ]
  • [ 1415638-39-9 ]
YieldReaction ConditionsOperation in experiment
79% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride; In 1,4-dioxane; water; at 45 - 65℃; for 5.5h;Inert atmosphere; General procedure: A stirred suspension of 5-bromo-4-(3,4,5-trimethoxyphenyl)-thiazole derivative 7a or 7c (0.5 mmol) and the appropriate phenylboronic acid (1 mmol) in dioxane (6 mL containing 3 drops of water) was degassed under a stream of nitrogen for 10 min, then treated with [1,10-bis(diphenylphosphino)ferrocene] dichloropalladium (II) methylene chloride complex (41 mg, 0.05 mmol) and cesium fluoride (190 mg, 1.25 mmol). The reaction mixture was heated under nitrogen at 45 C for 30 min, then at 65 C for 5 h. The reaction mixture was cooled to ambient temperature, diluted with CH2Cl2 (10 mL), filtered through a pad of celite and evaporated in vacuo. The residue was dissolved with CH2Cl2 (15 mL), and the resultant solution was washed sequentially with water (5 mL) and brine (5 mL). The organic layer was dried and evaporated, and the residue was purified by flash chromatography on silica gel.
  • 26
  • [ 488-48-2 ]
  • [ 22237-13-4 ]
  • [ 1417464-05-1 ]
YieldReaction ConditionsOperation in experiment
89% General procedure: To a mixture of 1 (0.21 g, 0.5 mmol), 2aeo (2.0 mmol), palladium catalyst [tetrakis(triphenylphosphine)] in an argon flushed pressure tubewas added THF (5 ml) and aqueous K2CO3 (2 ml, 2 M). The reaction mixture was refluxed for 12 h and was allowed to cool down to room temperature and then cold water (8 ml) was added. After stirring for additional 15 min, the mixture was extracted with dichloromethane (3 20 ml). The organic layer was washed with brine, dried over anhyd Na2SO4, filtered and concentrated in vacuo to give an inseparable 1:1 mixture of 3a-o and of the corresponding 2,3,5,6-tetraaryl-p-dihydrobenzoquinone. The mixture was treated with DDQ (0.85 mmol) in benzene (8.5 ml) and was stirred at room temperature for 3 h. The reaction mixture was filtered, dried (Na2SO4) and concentrated in vacuo. The residue was purified by chromatography (silica gel, heptanes/EtOAc¼9:1) to give products 3a-o.
  • 27
  • [ 908267-60-7 ]
  • [ 22237-13-4 ]
  • [ 1421589-68-5 ]
YieldReaction ConditionsOperation in experiment
70% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃; for 3h;Inert atmosphere; Synthesis of 7-Chloro-3- (4-ethoxyphenyl) imidazo[1 , 2-a]pyridine (compound 65-5)[0000231] A suspension of compound 65-4 (200 mg, 0.72 mmol, 1 equiv), Pd(PPh3)4 (41 mg, 0.036 mmol, 0.05 equiv), 4- ethoxyphenylboronic acid (121.5 mg, 0.73 mmol, 1.02 equiv), and sodium carbonate (152 mg, 1.4 mmol, 2 equiv) in 3:1 mixture of dioxane and water (20 mL) was degassed with a stream of nitrogen for 10 minutes. The reaction was heated at 90 C for 3 h, at which time LC-MS indicated the reaction was complete. Ethyl acetate (10 mL) was added and the layers were separated. The organic layer was dried over sodium sulfate, filtered through silica gel (2g) and the silica gel was washed with ethyl acetate (15 mL) . The filtrates were evaporated under reduce pressure and the product was triturated with methyl tert-butyl ether (3 mL) to give compound 65-5 as an off white solid. (130 mg, 70% yield)
  • 28
  • [ 22237-13-4 ]
  • [ 89581-87-3 ]
  • [ 1422527-97-6 ]
YieldReaction ConditionsOperation in experiment
76% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃; for 12h; General procedure: A mixture of the amide 2 (0.43 mmol), boronic acids 3 (1.3 mmol), Pd(PPh3)4 (0.043 mmol), and Na2CO3 (2.1 mmol) in 5 mL of a mixture of DME/H20 (3:1) in coated Kimble vials was stirred with orbital stirring at 110 C for 12 h. The resulting mixture was concentrated in vacuo and then ethyl acetate was added. This solution was washed with water and NaOH 1 N to remove the acid boronic excess. The organic layer was collected, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography or preparative method on silica gel.
  • 29
  • [ 55304-75-1 ]
  • [ 22237-13-4 ]
  • [ 1426922-07-7 ]
YieldReaction ConditionsOperation in experiment
78% With potassium phosphate; palladium diacetate; In water; N,N-dimethyl-formamide; at 20℃; for 12h; A DMF/water solution (1:1, 2 mL per 1 mmol of 1) of K3 PO4 (1.5 mmol),Pd(OAc)2 (2 mol %), and arylboronic acid 2a-n (0.9 mmol) was stirred atroom temperature for 8-12 h (tlc control). After completion of the reaction, themixture was extracted with CH2Cl2 and the combined organic layers weredried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residuewas purified by column chromatography (silica gel, EtOAc/heptane = 1:4).Starting with 1 (216 mg, 1.00 mmol), K3PO4 (165 mg, 1.50 mmol), Pd(OAc)2(2 mol %), 4-ethoxyphenylboronic acid (149 mg, 0.90 mmol), and a solution ofDMF and water (1:1, 5 mL), 3g was isolated as a white solid (235 mg, 78%),mp = 74-75 C. 1H NMR (300 MHz, CDCl3): d = 1.36 (t, 3H, CH3), 4.01 (q, 2H,CH2), 6.87 (d, J = 8.91 Hz, 2H, ArH), 7.30 (dd, J = 8.37, J = 0.75 Hz, 1H, ArH), 7.40(d, J = 8.46 Hz, 2H, ArH), 7.90 (d, J = 8.51 Hz, 1H, ArH). 13C NMR (75.46 MHz,CDCl3): d = 13.7 (CH3), 62.5 (OCH2), 113.1 (CH), 115.3 (d, 1JCF = 252.42 Hz, CF3),120.9 (CH), 122.0 (q, 2JCF = 63.26, Hz, C), 124.3(C), 126.6 (C), 127.9 (C), 129.1(C),129.3 (d, 4JCF 1.95 Hz CH), 136.6 (q, 3JCF = 5.01 Hz CH), 152.3 (C), 157.9 (d,JCF = 2.82 Hz, C), 159 (C). 19F NMR (282.4 MHz, CDCl3): d = 57.02 (CF). IR (ATR,cm 1): m = 3064 (w), 2980 (m), 2877 (w), 1660 (w), 1544 (w), 1140 (m), 816 (s).MS (EI, 70 eV): m/z (%) 301 (57) [M+], 273 (100), 238 (12). HRMS (EI) calcd forC14H11ClF3NO [M+]: 301.04758, found 301.04758.
  • 30
  • C42H37ClF6N4O20S2 [ No CAS ]
  • [ 22237-13-4 ]
  • C56H55ClN4O16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 32℃; for 5h;Inert atmosphere; Tetrakis(triphenylphosphine)palladium(0) (682 mg) was added to triflate 50 (11 g), <strong>[22237-13-4]4-ethoxybenzeneboronic acid</strong> (4.24 g) and sodium carbonate (5.4 g) in a mixture of toluene (220 mL), ethanol (110 mL) and water (110 mL). The reaction mixture was allowed to stir for 5 hours under an argon atmosphere at 32 C. During this time the product was observed to precipitate from the reaction mixture. The reaction mixture was diluted with ethyl acetate and washed with water, brine and dried over magnesium sulphate. After filtration excess ethyl acetate was removed by rotary evaporation under reduced pressure. The crude coupling product was purified by flash column chromatography (silica gel; gradient 50/50 ethyl acetate/hexane to 70/30 ethyl acetate/hexane). Pure fractions were combined and removal of excess eluent afforded the pure product 51 as an orange solid (8.6 g, 82% yield, LC/MS 3.72 mins, m/z ES+ 1063.25).
  • 31
  • [ 1666-13-3 ]
  • [ 22237-13-4 ]
  • 4-ethoxyphenyl-phenyl-selenide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% General procedure: Diphenyl diselenide (0.2 mmol), boronic acid (0.44 mmol), CuSO4 (3 mol %, 20 mg), 1,10-phen. H2O (3 mol %, 24 mg) were thrown into 25 mL oven-dried Schlenk tube. Then, EtOH (0.6 mL) was added with a syringe. After 1 min, Na2CO3 (5% aq) (0.1 mL or 1 mL) was added and the mixture stirred vigorously at room temperature for 5 h-22 h. After completion of the reaction, the reaction mixture was diluted with Et2O, filtered, washed with copious washings (Et2O or EtOAc), concentrated. The crude product was purified on a short silica gel column (ethyl acetate or petroleum ether).
  • 32
  • [ 1442084-12-9 ]
  • [ 22237-13-4 ]
  • 7-(4-ethoxyphenyl)-4-methyl-6-((trifluoromethanesulfonyl)oxy)-2H-chromen-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 70℃; for 6h; General procedure: A solution of K3PO4, Pd(PPh3)4,and arylboronic acid in the solvent indicated was stirred at the indicatedtemperature and for the indicated time. After cooling to 20 C, distilled H2Owas added. The organic and the aqueous layers were separated and the latterwas extracted with CH2Cl2. The combined organic layers were dried (Na2SO4),filtered, and the filtrate was concentrated in vacuo. The residue was purified bycolumn chromatography (flash silica gel, heptanes-EtOAc).
90% With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 70℃; for 6h;Inert atmosphere; General procedure: To a dioxane suspension (3 mL) of bis(triflate) analogue 5 (70 mg, 0.15 mmol), Pd(PPh3)4 (11mg, 6 mol%, 0.0092 mmol), and arylboronic acids 6 (0.34 mmol) was added K3PO4 (98mg, 0.46 mmol). The mixture was heated at 120 C under Argon atmosphere for 6 h. The reaction mixture was diluted with water and extracted with CH2Cl2 (3 × 25 mL). The combined organic layers were dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (silica gel, EtOAc/heptane).
  • 33
  • [ 1442084-12-9 ]
  • [ 22237-13-4 ]
  • [ 1442084-17-4 ]
YieldReaction ConditionsOperation in experiment
88% With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 120℃; for 6h; General procedure: A solution of K3PO4, Pd(PPh3)4,and arylboronic acid in the solvent indicated was stirred at the indicatedtemperature and for the indicated time. After cooling to 20 C, distilled H2Owas added. The organic and the aqueous layers were separated and the latterwas extracted with CH2Cl2. The combined organic layers were dried (Na2SO4),filtered, and the filtrate was concentrated in vacuo. The residue was purified bycolumn chromatography (flash silica gel, heptanes-EtOAc).
88% With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 120℃; for 6h;Inert atmosphere; General procedure: To a dioxane suspension (3 mL) of bis(triflate) analogue 5 (70 mg, 0.15 mmol), Pd(PPh3)4 (11mg, 6 mol%, 0.0092 mmol), and arylboronic acids 6 (0.34 mmol) was added K3PO4 (98mg, 0.46 mmol). The mixture was heated at 120 C under Argon atmosphere for 6 h. The reaction mixture was diluted with water and extracted with CH2Cl2 (3 × 25 mL). The combined organic layers were dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (silica gel, EtOAc/heptane).
  • 34
  • [ 1451071-95-6 ]
  • [ 22237-13-4 ]
  • [ 1451071-96-7 ]
YieldReaction ConditionsOperation in experiment
93% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 120℃; for 6h;Inert atmosphere; General procedure: A solution of 3 (50 mg,0.122 mmol), K2CO3 (2 M, 2 mL), Pd(PPh3)4 (6 mol %), and arylboronic acid 3(2.4 equiv) in 1,4-dioxane (3 mL) was stirred at 120 C for 6 h under argonatmosphere. To the reaction mixture H2O (20 mL) and CH2Cl2 (25 mL) wereadded. The organic and the aqueous layers were separated and the latter wasextracted with CH2Cl2 (2 20 mL). The combined organic layers were dried(Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue waspurified by column chromatography (silica gel, heptane/EtOAc).
  • 35
  • [ 1456896-15-3 ]
  • [ 22237-13-4 ]
  • [ 1456896-31-3 ]
YieldReaction ConditionsOperation in experiment
81% With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 70℃; for 18h;Inert atmosphere; General procedure: A 1,4-dioxane solution of 4b (0.13 mmol), arylboronic acid (1.0 equiv), K3PO4 (1.5 equiv) and Pd(PPh3)4 (3 mol %) was heated at 70 oC for 18 h under argon atmosphere. After cooling to 20 oC, CH2Cl2 (20 mL) was added, the solution was filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (EtOAc/Heptanes).
 

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