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Structure of 13331-23-2

Chemical Structure| 13331-23-2

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Product Details of [ 13331-23-2 ]

CAS No. :13331-23-2
Formula : C4H5BO3
M.W : 111.89
SMILES Code : OB(C1=CC=CO1)O
MDL No. :MFCD00799544
InChI Key :PZJSZBJLOWMDRG-UHFFFAOYSA-N
Pubchem ID :2734357

Safety of [ 13331-23-2 ]

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

Computational Chemistry of [ 13331-23-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 28.53
TPSA ?

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

53.6 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

-0.07
Log Po/w (WLOGP)?

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

-1.04
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.

-1.76
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

-1.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.81

Water Solubility

Log S (ESOL):?

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

-0.89
Solubility 14.5 mg/ml ; 0.13 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.

-0.6
Solubility 27.8 mg/ml ; 0.249 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

-0.44
Solubility 40.5 mg/ml ; 0.362 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.

-7.03 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

2.0
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)

2.65

Application In Synthesis of [ 13331-23-2 ]

* 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 [ 13331-23-2 ]

[ 13331-23-2 ] Synthesis Path-Downstream   1~19

  • 1
  • [ 13331-23-2 ]
  • [ 342777-09-7 ]
  • [ 939-57-1 ]
  • (E)-3-(2-Furan-2-ylmethyl-phenyl)-acrylic acid [ No CAS ]
  • 2
  • [ 13331-23-2 ]
  • [ 626-44-8 ]
  • 1,3,5-tri(furan-2-yl)benzene [ No CAS ]
  • 3
  • [ 13331-23-2 ]
  • N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide [ No CAS ]
  • [ 374790-93-9 ]
  • [ 1438429-57-2 ]
YieldReaction ConditionsOperation in experiment
353 mg of 2-furylboronic acid, 624 mg of sodium carbonate in 25 cm3 of water, and 311 mg of tetrakis(triphenylphosphine)palladium are added to 1.25 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, prepared in Example 63, in 125 cm3 of dioxane, and the mixture is refluxed for 18 hours, 611 mg of 2-furan-2-yl-4,4,5,5-tetramethyl[1,3,2]dioxaborolane are then added and heating is continued for 4 hours at reflux. 75 cm3 of ethyl acetate and 75 cm3 of water are added and the reaction medium is filtered through a sinter funnel packed with Celite. The organic phase is separated out after settling of the phases has taken place, washed with 75 cm3 of water, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50 C.) to give 2 g of an oil, which is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 mum; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (75/25 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50 C.) to give 1.20 g of N-[5-(2-furyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a beige-coloured solid. [0886] 1H NMR spectrum (300 MHz, (CD3)2SO-d6, delta in ppm): -0.09 (s: 9H); 0.82 (t, J=8 Hz: 2H); 0.97 (t, J=7.5 Hz: 3H); 1.68 (mt: 2H); 2.43 (t, J=7 Hz: 2H); 3.55 (t, J=8 Hz: 2H); 5.17 (s: 2H); 5.61 (d, J=3.5 Hz: 1H); 5.68 (broad s: 2H); 6.38 (dd, J=3.5 and 1.5 Hz: 1H); 7.07 (d, J=8.5 Hz: 2H); 7.19 (d, J=8.5 Hz: 2H); 7.36 (broad t, J=7.5 Hz: 1H); 7.43 (broad t, J=7.5 Hz: 2H); 7.50 (broad d, J=7.5 Hz: 2H); 7.59 (s: 1H); 7.61 (d, J=1.5 Hz: 1H); 8.20 (s: 1H); 10.58 (unresolved peak: 1H). [TABLE-US-00057] EI m/z = 581M+. m/z = 464[M - OCH2CH2Si(CH3)3]+ m/z = 91[C6H5CH2]+
  • 4
  • [ 13331-23-2 ]
  • [ 18995-35-2 ]
  • [ 1158984-98-5 ]
YieldReaction ConditionsOperation in experiment
98% Under ambient atmosphere, to a 40 mL I-Chem vial equipped with a stir bar was added 1-te/t-butoxy-4-chlorobenzene (3a) (0.185 g, 1.00 mmol), dicyclohexylphosphino^δ'-dimethoxy-I J '-biphenyl (SPhos) (41 mg, 0.10 mmol) and Pd(OAc)2 (11 mg, 0.050 mmol). The vial was sealed with a PTFE-lined septum screw- cap, and then placed under an Ar atmosphere. To the vial was added dioxane (9.5 mL) and the resulting mixture was stirred at 23 0C for 10 min. To the vial was added aqueous K3PO4 (3.0 M, 2.5 mL, degassed by sparging with Ar for 30 min). The vial was placed in a 60 0C oil bath, and to the stirred mixture was added dropwise over 3 h via syringe pump freshly prepared 2-furylboronic acid (1a) (0.1 12 g, 1.00 mmol) as a solution in dioxane (3.0 mL). After the addition was complete the reaction mixture was stirred at 60 0C for an additional 3 h. The mixture was cooled to room temperature and was then transferred to a 60 mL separatory funnel and was diluted with aqueous NaOH (1.0 M, 10 mL). The mixture was extracted with Et2θ (3 x 10 mL). The combined organic fractions were dried over MgSO4, filtered and then concentrated in vacuo. The resulting residue was purified by flash chromatography (hexanes: EtOAc, 100:0 -> 9:1) to afford a colorless oil (0.213 g, 98%).
YieldReaction ConditionsOperation in experiment
Under ambient atmosphere, to a 25 mL Schlenk flask equipped with a stir bar was added 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos) (41 mg, 0.10 mmol), Pd(OAc)2 (1 1 mg, 0.050 mmol) and freshly-prepared 2-furylboronic acid (1a) (106 mg, 0.949 mmol). The flask was placed under Ar atmosphere and to the flask was added dioxane (12.5 mL). To the solution was added dodecane (100 microliters, internal standard) and 1 -te/t-butoxy-4-chlorobenzene (3a) (175 microliters, 0.980 mmol), and the solution was stirred at 23 0C for 10 minutes. The solution was sampled and analyzed by GC to determine the ratio of halide:dodecane. To the dark amber solution was added aqueous K3PO4 (3.0 M, 2.5 mL, degassed by sparging with Ar for 30 min) and the dark mixture was stirred for 5 minutes. The organic phase was sampled as the initial time-point (t = 0), and the mixture was then immediately placed in a 60 0C oil bath with stirring. The organic phase was sampled periodically and the consumption of the halide was determined by GC analysis versus the internal standard. FIG. 4 depicts a graph of the data for cross-coupling conversion of 2-furyl boronic acid 1a with 1-te/t-butoxy-4-chlorobenzene 3a.
  • 6
  • [ 13331-23-2 ]
  • [ 25961-11-9 ]
  • [ 1251914-05-2 ]
  • 7
  • [ 13331-23-2 ]
  • [ 1122-91-4 ]
  • [ 60456-77-1 ]
YieldReaction ConditionsOperation in experiment
95% With tetrabutylammomium bromide; potassium carbonate; In methanol; water; at 80℃; for 0.25h;Reflux; General procedure: A mixture of hetarylboronic acid 4a-d(1.2 mmol), aryl(hetaryl) bromide 5a-h or hetaryl chloride7a,b (1 mmol), Bu4NBr (3 mg, 1 mol %, for water-insolublearyl(hetaryl) halides 5b-g and 7a,b), and K2CO3 (346 mg,2.5 mmol) in 2 (5 ml) was heated to 80 and treated byadding 0.1-1 mol % of Pd-Ni(Co)-B-L (an aliquot of0.1 M solution of bimetallic catalyst in MeOH-H2Omixture). The reactor was fitted with a reflux condenserand placed in a hot silicone oil bath (150). The reactionmixture was vigorously stirred at reflux until completeconversion of the starting materials was achieved. Thereaction progress was controlled by TLC method (eluenthexane-Et2O, 3:1). The amount of catalyst, reactionduration and yields of the target compounds 6a-k are listedin Table 4. In the case of the activated aryl bromides5a,b,d,f, the reaction was highly exothermic, therefore aneffective reflux condenser was essential for scaling up thissynthesis.After the reaction was complete, the mixture was dilutedwith H2O (10 ml), heated to 80C, and filtered while hotthrough a Whatman autovial syringeless filter (pore size0.45 μm). The filtrate was diluted with 10-15 vol % ofEtOH, heated to ~50C, stirred, and slowly acidified with5% HCl to pH 2-3. The resulting precipitate was easy tofilter, and analytically pure products 6a,h,k were obtainedwithout chromatographic purification. In the case of thewater-insoluble heterobiaryls 6b-g,i,j, the reaction mixturewas diluted with saturated solution of NaCl (10 ml) andextracted with Et2O or EtOAc (3×5 ml). The obtainedextract was dried over anhydrous Na2SO4, filtered througha silica gel layer, and the solvent was evaporated at reducedpressure. The residues in all cases were >99% pureproducts (according to the results of elemental analysis).Analytically pure samples were obtained by recrystallizationof heterobiaryls 6a-k from a minimal amount ofaqueous EtOH (10-20% 2) or by converting amines intothe respective hydrochlorides. The residual metal content inthe isolated heterobiaryls 6a-k did not exceed 1 ppmaccording to the results of atomic absorption spectrometry.
84% In a 100 mL three-necked flask, 2-furanboronic acid (0.559 g, 5 mmol), 4-bromobenzaldehyde (0.925 g, 5 mmol), K2CO3 (0.696 g, 1 N) and N,N-dimethylformamide (10 mL) ). First, stir for 30 minutes under N2 atmosphere.The air remaining in the reactor was removed, and then palladium acetate (9 mg), triphenylphosphine (60 mg) was added. The reaction was carried out at 90 C for 6 hours. After the reaction was completed, it was cooled to room temperature, dissolved in dichloromethane and washed sequentially with water (50 ml). Finally, it was purified by column chromatography, and the product was dark green oil (0.65 g).The yield was 84%.
47% With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In ethanol; water; toluene;Reflux; General procedure: Tetrakis(triphenylphosphine)palladium(0) (0.0168 mmol) was added to a solution of 4-bromobenzaldehyde (50, 5.6 mmol) in ethanol-toluene (40 mL, 1:1). After 15 min, the appropriate boronic acid 51b-m (6.75 mmol) was added, followed by sodium hydrogen carbonate (22.4 mmol) and water (11 mL). The resulting mixture was heated under reflux for 9-15 hours. After cooling, the reaction mixture was filtered through Celite, the organic phase was separated, washed with brine (2x20 mL), dried and the solvent evaporated in vacuo. The residue thus obtained was purified by flash-chromatography. Elution by light petroleum-ethyl acetate mixtures afforded the desired compounds.
  • 8
  • [ 1899-24-7 ]
  • [ 13331-23-2 ]
  • [ 16303-60-9 ]
YieldReaction ConditionsOperation in experiment
77% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; at 70℃;Inert atmosphere; Sealed tube; General procedure: A bromo-aldehyde (1 mmol), boronic acid (1.1e1.3 mmol), tetrakis(triphenylphosphine)palladium (0.05 mmol), potassium carbonate(3 mmol), water (3 ml), ethanol (4 ml) and toluene (4 ml)were added to a round-bottomed flask. The reaction mixture wasflushed with argon, sealed under septa and heated at 70 C overnight.After cooling to room temperature, water (50 ml) was added,and product was extracted with ethyl acetate (3 x 50 ml). Combinedextracts were washed with brine, dried with anhydrousmagnesium sulfate and evaporated under reduced pressure. Theproduct was purified by column chromatography on silica withchloroform or a mixture of methanol and chloroform (1:9).
  • 9
  • [ 13331-23-2 ]
  • [ 4532-25-6 ]
  • 7-(furan-2-yl)imidazo[1,2-a]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; tricyclohexylphosphine; In water; N,N-dimethyl-formamide; at 130℃; for 1h;Inert atmosphere; Microwave irradiation; General procedure: <strong>[4532-25-6]7-chloroimidazo[1,2-a]pyridine</strong> (5) (300 mg, 1.97 mmol) was dissolved in 8:1 DMF:H2O (13.1 mL) in a microwave vial affixed with a magnetic stir bar. Thiophen-2-ylboronic acid was added followed by sodium carbonate (834 mg, 7.86 mmol). The reaction mixture was degassed with argon. Pd2(dba)3 (36 mg, 0.039 mmol) and P(Cy)3 (33 mg, 0.118 mmol) was added to the reaction mixture and the vial was sealed. The reaction was heated by microwave irradiation to 130 C for 1 h. After, the reaction mixture was diluted with ethyl acetate and washed three times with saturated sodium bicarbonate and three times with deionized water. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed in vacuo. The crude product was absorbed onto silica. The product was purified via flash chromatography utilizing a DCM/MeOH gradient and isolated as a brown solid (223 mg, 59%).
  • 10
  • [ 13331-23-2 ]
  • [ 618-89-3 ]
  • methyl 3-(furan-2-yl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In methanol; toluene; at 100℃; for 16h;Inert atmosphere; General procedure: According to a procedure by Oxford et al.,[3] furan-2-boronic acid (168 mg, 1.5 mmol, 1.5 eq), aryl halide (1.0 mmol, 1.0 eq), Pd(PPh3)4 (116 mg, 0.1 mmol, 10 mol%) and cesium carbonate (350 mg, 1.1 mmol, 1.1 eq) were suspended in a toluene/MeOH mixture (4:1, 10 mL). The reaction mixture was stirred for 16 h at 100 C. The reaction mixture was diluted with EtOAc (8 mL) and the organic layer was extracted was washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography.
70% General procedure: A solution of sodium carbonate (0.55mmol) in water (1.75mL) and EtOH (1.25mL) was prepared and degassed. In a 10mL vial Tetrakis (triphenylphosphine) palladium (0.055mmol) was added to a solution of 4a-e (0.275mmol) in DME (5mL) in a 10mL vial. Argon was bubbled into the DME solution with stirring for 10min. The boronic acid (1.650mmol) was added to the vial followed by the addition of the sodium carbonate mixture. The vial was sealed under argon and heated to 80C while stiring for 12h. The mixture was diluted in water and extracted with ethyl acetate. The extracts were washed with brine and dried over magnesium sulfate. The mixture was concentrated in vacuo to give the product as an oil. The product was purified in by column chromatography and characterized by 1H and 13C NMR.
  • 11
  • [ 13331-23-2 ]
  • [ 58530-13-5 ]
  • 3-(furan-2-yl)-5-methylbenzoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
34% With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; water; at 80℃; for 0.5h;Inert atmosphere; Microwave irradiation; To a degassed souton of 9:1 1 ,4-doxane:H2O (4 mL) was added 3-bromo-5-methythenzoc acid (0.300 g, 1.395 mmo), 2-furanboronc acid (0.187 g, 1.674 mmo), K2C03 (0.289 g, 2.093 mmo) and PdC2(PPh3)2 (0.049 g, 0.070 mmo), under an atmosphere of nitrogen. Thereaction was rradated n a CEM microwave reactor at 80 C for 30 mn, then cooed and passed through a pad of Cehte. The Cehte was washed with a portion of EtOAc (10 mL) and the entire mxture was concentrated to dryness. The residue was taken up n DCM (20 mL) and an aq. son. of 2 M HC (20 mL) was added. The two ayers were separated, and the aqueous ayer was further extracted with DCM (2 x 20 mL). The organcs were combined,washed wth brine, dried (Na2SO4) and concentrated n vacuo. The crude matera waspurfied by sWca g& chromatography (soera Botage, 24 g S Cartrdge, 0-40% EtOAc npetroeum benzne 40-60 C) with the fracUons contanng suspected product coflected andconcentrated n vacuo to yed 3-(furan-2-y)-5-methybenzoc acd (M4)(0.095 g, 34 % yed)as a white sohd. 1H NMR (400 MHz, CDC3): 6 8.24 8.20 (m, 1 H), 7.85 7.81 (m, 1 H), 7.777.71 (m, 1H), 7.50 (dd, J = 1.8, 0.8 Hz, 1H), 6.74 (dd, J = 3.4, 0.7 Hz, 1H), 6.50 (dd, J =3.3, 1.8 Hz, 1H), 2.46 (s, 3H).
  • 12
  • [ 868066-91-5 ]
  • [ 13331-23-2 ]
  • 5-(furan-2-yl)-2-methylisoindolin-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; General procedure: 5-Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solutionof 2 M Na2CO3 (3 mL) and Pd(dppf)Cl2 (94 mg, 0.12 mmol) were added and the entiremixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30mmol) was added and reflux continued under N2 overnight. Upon cooling, the mixture wasdiluted with water (100 mL) and extracted with CH2Cl2 (6x50 mL). The combined organicfractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure togive a crude solid which was purified by flash column chromatography on silica gel (EtOAcas eluant). The title compound was isolated as a light-brown solid (510 mg, 97percent).
  • 13
  • [ 13331-23-2 ]
  • [ 13790-39-1 ]
  • 4-(furan-2-yl)-6,7-dimethoxyquinazoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With potassium phosphate; (DPEPhos)Ni(mesityl)Br; water; In 1,4-dioxane; benzene; at 25℃; for 16h;Inert atmosphere; Sealed tube; General procedure: Unless otherwise specified, under an inert atmosphere C1 (12.7mg, 0.016 mmol, 2 mol %), aryl halide (0.8 mmol), boronic acid(1.6 mmol), and K3PO4 (679 mg, 3.2 mmol) were added to anoven-dried 4 dram vial containing a magnetic stir bar. 1,4-Dioxane (1.3 mL) and benzene (700 μL) were added, the vial wassealed with a screwcap featuring a PTFE/silicone septum andwas removed from the glovebox. Degassed water (86 μL) wasadded via a gas-tight syringe. The reaction mixture was magneticallystirred for 16 h at room temperature. Note: On severaloccasions the base became clumpy and stuck to the bottom ofthe reaction vial; in these cases it was noted that reactions weremore successful if efficient stirring was maintained. After 16 h,the reaction mixture was taken up in EtOAc (ca. 10 mL) andextracted with distilled water (3 × 10 mL). The organic layer wasdried over anhydrous Na2SO4, filtered, and concentrated withthe aid of a rotary evaporator.
  • 14
  • [ 13331-23-2 ]
  • [ 16870-28-3 ]
  • 4-(2-furyl)-2-hydroxybenzoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With palladium diacetate; potassium carbonate; triphenylphosphine; In water; N,N-dimethyl-formamide; at 100℃; for 3h;Microwave irradiation; Inert atmosphere; Sealed tube; <strong>[16870-28-3]2-hydroxy-4-iodobenzoic acid</strong> (50 mg, 0.189 mmol), 2-furylboronic acid (38.6 mg, 0.227 mmol), PPh3 (7.4 mg, 0.028 mmol), K2CO3 (91.4 mg, 0.662 mmol), Pd(AcO)2 (2.12 mg, 0.0095 mmol), 1:1 DMF: H2O (2 ml) were used. Mobile phase for elution in flash chromatography AcOEt: CH3CN:H2O:CH3OH 70:5:2.5:2.5. Yield after purification: 50 % (25 mg). 1H NMR (400 MHz, acetone-d6) delta 11.19 (bs, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.72 (m, 1H), 7.31 (dd, J = 8.3, 1.6 Hz, 1H), 7.27 (d, J = 1.6 Hz, 1H), 7.07 (d, J = 3.4 Hz, 1H), 6.61 (dd, J = 3.5, 1.8 Hz, 1H). 13C NMR (101 MHz, acetone-d6) delta 172.4 (CO), 163.4 (C), 153.2 (C), 144.8 (CH), 138.4 (C), 131.9 (CH), 115.4 (CH), 113.1 (CH), 112.2 (CH), 111.8 (C), 109.4 (CH). HRMS (TOF, ES-): Calculated for C11H7O4 (M-H)-: m/z 203.0344. 203.0350 found (deviation 3.0 ppm). m.p. (C) > 220.
  • 15
  • [ 13331-23-2 ]
  • [ 33332-28-4 ]
  • [ 925677-91-4 ]
YieldReaction ConditionsOperation in experiment
80% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 100℃; for 18h;Inert atmosphere; To a solution of 6-chloropyrazin-2-amine (1.00 g, 7.75 mmol, 1 eq.) in a solution of toluene and ethanol (20 mL, 1:1) was added furan-2-ylboronic acid (0.955 g, 8.52 mmol, 1.1 eq.), Na2CO3 (1.479 g, 13.95 mmol, 1.8 eq.) in H2O (10 mL), Pd(PPh3)4 (0.223 g, 0.193 mmol, 0.025 eq.). The reaction mixture was deoxygenated using N2 atmosphere and the reaction mixture was heated at 100° C. for 18 h. The reaction was monitored by NMR. The reaction mixture was filtered through Celite with wash of ethyl acetate (2*20 mL). The reaction mixture was diluted with water (50 mL) and extracted using ethyl acetate (2*50 mL). The separated organic layer was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by CombiFlash on silica gel to afford 1.00 g (80percent) of 6-(furan-2-yl)pyrazin-2-amine.
  • 17
  • [ 13331-23-2 ]
  • [ 1458-01-1 ]
  • methyl 3,5-diamino-6-(furan-2-yl)pyrazine-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; toluene;Inert atmosphere; Reflux; General procedure: <strong>[1458-01-1]Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate</strong> 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.
  • 18
  • [ 13331-23-2 ]
  • [ 25015-63-8 ]
  • [ 374790-93-9 ]
  • 19
  • [ 13534-90-2 ]
  • [ 13331-23-2 ]
  • 3-bromo-4-(furan-2-yl)pyridine [ No CAS ]
 

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Technical Information

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[ 13331-23-2 ]

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