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Chemical Structure| 501945-71-7 Chemical Structure| 501945-71-7

Structure of 501945-71-7

Chemical Structure| 501945-71-7

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Product Details of [ 501945-71-7 ]

CAS No. :501945-71-7
Formula : C14H17BO2S
M.W : 260.16
SMILES Code : CC1(C)C(C)(C)OB(C2=CC=C3C(C=CS3)=C2)O1
MDL No. :MFCD05664405
InChI Key :YFTHTJAPODJVSL-UHFFFAOYSA-N
Pubchem ID :2795455

Safety of [ 501945-71-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 501945-71-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 9
Fraction Csp3 0.43
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 78.3
TPSA ?

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

46.7 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

3.93
Log Po/w (WLOGP)?

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

3.2
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.

2.37
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

3.54
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.61

Water Solubility

Log S (ESOL):?

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

-4.23
Solubility 0.0152 mg/ml ; 0.0000585 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.61
Solubility 0.00639 mg/ml ; 0.0000245 mol/l
Class?

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

Moderately 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

-4.94
Solubility 0.00296 mg/ml ; 0.0000114 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

Yes
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

Yes
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

Yes
Log Kp (skin permeation)?

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

-5.1 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<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)

3.0

Application In Synthesis of [ 501945-71-7 ]

* 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 [ 501945-71-7 ]

[ 501945-71-7 ] Synthesis Path-Downstream   1~34

YieldReaction ConditionsOperation in experiment
79% With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium acetate; In N,N-dimethyl-formamide; at 100℃; for 4h;Inert atmosphere; General procedure: A suspension of 6-bromo-benzothiazole (300 mg, 1.40 mmol), bis(pinacolato)diboron (427 mg, 1.68 mmol) and potassium acetate (KOAc)(412 mL, 4.20 mmol) in N,N-dimethylformamide (DMF, 6 mL) was added to PdCl2(dppf)2 (57 mg, 0.07 mmol), and the mixture was stirred at 100 C under N2 for 4 hours. After cooling to room temperature, the mixture was diluted with brine and EtOAc, and stirred for 5 minutes. After separating the organic layer, the aqueous layer was extracted three times with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and concentrated under a reduced pressure. The residue was purified by MPLC on silica gel eluting with EtOAC/hexane (1/20) to obtain the title compound (329 mg, 90%) as a white solid. 1H NMR (300 MHz, CDC13) delta 9.06 (s, 1H), 8.46 (s, lH), 8.13 (d, 1H), 7.94 (d, 1H), 1.38 (s, 12H).
<Step 1> Synthesis of 2-(benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 2-(benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane was obtained by performing the same procedure as in <Step 1> of Preparation Example 1, except that 5-bromobenzo[b]thiophene was used instead of 6-bromo-1H-indole. 1H-NMR: delta 1.24 (s, 12H), 7.65 (d, 1H), 7.85 (d, 1H), 7.98 (d, 1H), 8.07 (d, 1H), 8.12 (s, 1H)
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 100℃; for 15h;Inert atmosphere; General procedure: A mixture of 6-bromo-1 /-/-indazole (700 mg; 3.55 mmol), 4,4,4',4',5,5,5',5'-octamethyl- 2,2'-bi(1 ,3,2-dioxaborolane) (1 .50 g; 5.91 mmol), Pd(dppf)CI2- DCM (290 mg; 0.36 mmol) and KOAc (1 .04 g; 10.6 mmol) in DMF (20 mL) was stirred at 100C for 15 hours under nitrogen. The mixture was concentrated in vacuo, suspended in EtOAc (30 mL), filtered through Celite, and concentrated to afford 866 mg (100%) of the title compound as a brown semi-solid, which was used directly without further purification. LC-MS for Ci3H17BN2O2+H+ [M+H]+: calcd. 245.1 ; found: 245.0.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere; General procedure: Under a nitrogen stream, 5-bromo-1H-indole (25g, 0.128mol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-(1,3,2-dioxaborolane) (48.58g, 0.191mol), Pd(dppf)Cl2 (5.2g, 5mol), KOAc (37.55g, 0.383mol) and a mixture of DMF (500ml), 12 hours with stirring at 130 C. After completion of the reaction, and extracted with ethyl acetate, to remove water with MgSO4, is purified by Karamukuro Matogurafi (Hexane: EA = 10: 1 (v / v)) was obtained 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-1H-indole (12.43g, 40% yield).
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium acetate; In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere; General procedure: 5-bromo-1H-indole (25 g, 0.128 mol) was added under a nitrogen stream, 4,4,4 ', 4', 5,5,5 ', 5'-octamethyl-2,2'-bi (1,3,2-dioxaborolane)(48.58 g, 0.191 mol), Pd (dppf) Cl2 (5.2 g, 5 mol), KOAc (37.55 g, 0.383 mol) andWere mixed DMF (500 ml) And the mixture was stirred at 130 DEG C for 12 hours.After the reaction was completed, the reaction mixture was extracted with ethyl acetate, the water was removed with MgSO4,Purification by column chromatography (Hexane: EA = 10: 1 (v / v)) gave5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-indole(12.43 g, yield 40%).

  • 2
  • [ 4923-87-9 ]
  • [ 73183-34-3 ]
  • [ 501945-71-7 ]
YieldReaction ConditionsOperation in experiment
86% With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dimethyl sulfoxide; at 20 - 80℃; for 3h; Dissolve 5-bromo-benzo [b] thiophene (J. Mater. Chem., 10: 2069-2081,2000 ; 49 g, 7.0 mmol) in DMSO (40 mL). Add bis (pinacolato) diboron (7 mmol), PdCl2 (dppf)-CH2Cl2 (0.33 mmol), and KOAc (20 mmol). Flush the flask with N2, and then heat the reaction mixture to 80C with stirring. Continue to heat the reaction mixture for 3 hours, and then cool to room temperature. Add water (66 mL) and extract the aqueous layer with EtOAc (3 x 66 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 0-5% Et20/pentane) to give 1.56 g of the title compound (86%).
64% With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dimethyl sulfoxide; at 85℃; for 1.5h; Step E: Bis(pinacolato)diboron (1.3 g, 5.12 mmol), dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane (0.1 g, 0.14 mmol) and potassium acetate (1.4 g, 14.26 mmol) were charged in a 100 ml 3 neck round-bottomed flask which had been dried with a heat gun under vacuum and cooled under nitrogen prior to use. The mixture was degassed with nitrogen three times. A solution of 5-bromothiophene (1.0 g, 4.69 mmol) in dimethyl sulfoxide (20 ml) was added, the mixture was degassed again three times and was stirred at 85 C. for 1.5 hours. After cooling to room temperature, the mixture was filtered through diatomaceous earth and rinsed with water and ethyl acetate. Additional water was added to the filtrate which was extracted with ethyl acetate three times. The combined organic extracts were washed with brine once and dried over sodium sulfate to give the desired material (0.8 g, 64%, 100% AUC GC) after chromatography (9:1 to 5:1 heptane/ethyl acetate): 1H NMR (300 MHz, CDCl3) delta 8.24 (s, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.68 (dd, J=8.1, 0.6 Hz, 1H), 7.34 (d, J=5.4 Hz, 1H), 7.28 (dd, J=5.4, 0.6 Hz, 1H), 1.30 (s, 12H).
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dioxane 1-4; at 100℃; for 20h; EXAMPLE 10A 2-Benzo[b]thiophen-5-yl-4,4,5,5-tetramethyl-[3.2.1]dioxaborolane A mixture of 5-bromo-benzo[b]thiophene (Maybridge, 4.26 g, 0.0200 mol), bis(pinacolato)diboron (Aldrich, 6.09 g, 0.0240 mol) and potassium acetate (Aldrich, 2.94 g, 0.0300 mol) in 1,4-dioxane (Aldrich, 50 mL) was degassed and purged with N2 three times. [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) PdCl2(dppf).CH2Cl2 (300 mg, 0.4 mmol, Aldrich) was and the solution was heated to 100 C. for 20 hours. The mixture was then cooled to room temperature, diluted with 300 mL of EtOAc and washed with brine (2*20 mL). The organic solution was concentrated under reduced pressure and the residue was chromatographed to provide the title product. 1H NMR (300 MHz, CDCl3) delta 1.36-1.41 (S, 12H), 7.35 (d, J=5.50 Hz, 1H), 7.42 (d, J=5.70 Hz, 1H), 7.75 (d, J=8.14 Hz, 1H), 7.89 (d, J=8.14 Hz, 1H), 8.31 (s, 1H) ppm. MS (DCI/NH3) m/z 278 (M+H)+.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere; Instead of 6-bromo -1H- indole, 5-bromobenzo [b] but using thiophene, as in Preparation Example 1 above 2- (benzo [b] thiophen-5-yl ) 4,4,5,5 to obtain a tetra-methyl-1,3,2-dioxaborolane.

  • 3
  • [ 648904-46-5 ]
  • [ 501945-71-7 ]
  • [ 648905-40-2 ]
YieldReaction ConditionsOperation in experiment
93% Dissolve 2-benzo [b] thiophen-5-yl-4,4, 5, 5-tetramethyl- [1, 3, 2] dioxaborolane (400 mg, 1.54 mmol) and the compound of Preparation 1 (270 g, 0. 51 mmol) in CH3CN (24 mL). Add Pd (OAc) 2 (0.05 mmol), tricyclohexylphosphine (0.075 mmol), and CsF (4.5 mmol). Flush the flask with N2, then heat the reaction mixture to 90C with stirring. Continue to heat the reaction mixture for 6 hours, and then cool to room temperature. Add water (50 mL), and extract the aqueous layer with CH2CI2 (3 x 25 mL). Combine the organic layers and dry with Na2S04, filter, concentrate and purify by flash column chromatography (silica gel, 0-4% MeOH-NH40H (10/1, v/v) in CH2CI2) to give 240 mg of the title compound (93%) : 1H NMR (CDC13) 8 7.99 (d, J = 1. 2 Hz, 1H), 7. 88 (d, J = 9.2 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7. 58 (dd, J = 8.4, 1. 2 Hz, 1H), 7.41 (d, J = 5.6 Hz, 1H), 7.31 (d, J = 5. 6 Hz, 1H), 7.21 (d, J = 2.8 Hz, 1H), 7. 11. (dd, J = 9.2, 2. 8 Hz, 1H), 6.73 (d, J = 5.6 Hz, 1H), 6.60-6. 63 (m, 4H), 4. 04 (t, J= 5. 0 Hz, 2H), 3.94 (s, 3H), 2.93 (t, J =5. 0 Hz, 2H), 2.67-2. 79 (m, 4H), 1. 66-1.75 (m, 4H), 1. 44-1. 55 (m, 2H).
  • 4
  • [ 501945-71-7 ]
  • [ 877263-71-3 ]
  • [ 877263-72-4 ]
YieldReaction ConditionsOperation in experiment
88% With sodium carbonate;palladium diacetate; triphenylphosphine; In 1,2-dimethoxyethane; water; at 80℃; for 15h; Step F: An aqueous solution of sodium bicarbonate (4.30 ml, 2 M) was added to a solution of the bromoisoquinoline from Step D (0.64 g, 2.9 mmol), the product from Step E (0.75 g, 2.9 mmol) and triphenylphosphine (0.30 g, 1.2 mmol) in DMF (20 ml) at room temperature. The resulting mixture was degassed with nitrogen three times. Palladium(II) acetate (0.07 g, 0.3 mmol) was added, the mixture was degassed with nitrogen three times and stirred at 80 C. for 15 hours. After cooling to room temperature, the mixture was filtered through diatomaceous earth and rinsed with water and ethyl acetate. The filtrate was washed with water twice and brine, and dried over magnesium sulfate to give the desired coupled isoquinoline (0.70 g, 88%) after chromatography (5:1 to 3:1 heptane/ethyl acetate): 1H NMR (300 MHz, CDCl3) delta 7.94 (d, J=8.4 Hz, 1H), 7.88 (d, J=1.2 Hz, 1H), 7.75-7.78 (m, 2H), 7.47 (d, J=5.4 Hz, 1H), 7.40-7.44 (m, 2H), 7.34 (d, J=5.4 Hz, 1H), 2.50 (s, 3H).
  • 5
  • [ 501945-71-7 ]
  • [ 845872-49-3 ]
YieldReaction ConditionsOperation in experiment
With boron trichloride; In dichloromethane; at -78℃; for 0.25h; A solution of 0.6 g of <strong>[501945-71-7]2-(1-benzothiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> in 2.5 ml of dichloromethane is added dropwise to a solution of boron trichloride in dichloromethane (1 M, 14.3 ml) at -78C. After 15 minutes, the reaction mixture is warmed to room temperature, and 8 ml of methanol are added dropwise. It is then evaporated to dryness and dried under high vacuum overnight. 0.350 g of the title compound is obtained as a grey powder. Rt = 3.33.
A solution of 0.6 g of 2-(l-benzothiophen-5-yl) 4,4,5,5-tetramethyl-1,3,2-dioxaborolane in 2.5 m of dichloromethane is added dropwise to a solution of boron trichloride in dichloromethane (1M, 14.3 ml) at -78 C. After 15 minutes, the reaction mixture is warmed to room temperature, and 8 ml of methanol are added dropwise. It is then evaporated to dryness and dried under high vacuum overnight. 0.350 g of the title compound is obtained as a grey powder Rt=3.33.
A solution of 0.6 g of 2-(1-benzothiophen-5-yl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane in 2.5 ml of dichloromethane is added dropwise to a solution of boron trichloride in dichloromethane (1M, 14.3 ml) at -78C. After 15 minutes, the reaction mixture is warmed to room temperature, and 8 ml of methanol are added dropwise. It is then evaporated to dryness and dried under high vacuum overnight. 0.350 g of the title compound is obtained as a grey powder. Rt = 3.33.
  • 6
  • [ 109-01-3 ]
  • [ 501945-71-7 ]
  • [ 298-12-4 ]
  • [ 1092477-35-4 ]
YieldReaction ConditionsOperation in experiment
13% Intermediate 7: (+/-)-1-benzothien-5-yl(4-methyl-1-piperazinyl)acetic acid hydrochloride; <n="52"/>To a solution of 390 mg of 2-(1-benzothien-5-yl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (1.5 mmole, Maybridge) in 5.0 ml. of dry MeCN, at RT, were added 138 mg of glyoxylic acid hydrate (1.5 mmole, Aldrich) and 166 mul_ of 1-methylpiperazine (1.5 mmole, Aldrich). The mixture was subjected to microwave irradiation (12O0C, 20 minutes) and was cooled down to RT. The solvent was evaporated and the residue dissolved in 1 ml. of HCI aq. 1 N and purified on HLB-LP extraction cartridges (from water to water/MeOH 7:3 as an eluent). The eluent was evaporated under reduced pressure to give the title compound as a yellow foam (55 mg, 13%); 1H-NMR (400MHz, DMSOd6): delta 2.35 (3H, s), 2.81 (4H, s), 3.33 (4H, s), 4.16 (1 H, s), 7.42 (1 H, d), 7.49 (1 H, d), 7.80 (1 H, d), 7.91 (1 H, s), 8.00 (1 H, d); m/z (ES): 291.1 [M+H]+.
  • 7
  • [ 501945-71-7 ]
  • [ 1631-26-1 ]
  • [ 1082525-31-2 ]
  • 8
  • [ 501945-71-7 ]
  • [ 1258933-18-4 ]
  • [ 1258933-17-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; CyJohnPhos; In 1,4-dioxane; ethanol; water; at 20 - 150℃; for 0.25h;microwave irradiation; Example 8B 4-[6-(1-benzothien-5-yl)pyridazin-3-yl]-1,4-diazatricyclo[4.3.1.13,8]undecane A microwave-safe vial was charged with the product from Example 8A (0.060 g, 0.23 mmol), <strong>[501945-71-7]2-(benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (0.0825 g, 0.32 mmol; Maybridge), dichlorobis(triphenylphosphine)palladium (0.016 g, 0.023 mmol; Aldrich), (2-biphenyl)dicyclohexylphosphine (0.0024 g, 0.0068 mmol; Aldrich), and 3 mL 1:1:1 ethanol-dioxane-1 M sodium carbonate solution. The mixture was stirred for 5 minutes at room temperature, then heated in a microwave reactor at 150 C. (300 W) for 10 minutes. The reaction was filtered, concentrated, and purified by flash chromatography on silica gel, eluding with 5-10% methanol (containing 1% ammonium hydroxide)-chloroform to afford the title compound: MS (DCI/NH3) m/z 363 (M+H)+.
  • 9
  • [ 501945-71-7 ]
  • [ 1418306-01-0 ]
  • [ 1418306-15-6 ]
YieldReaction ConditionsOperation in experiment
19% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 100℃; for 16h;Inert atmosphere; Pd(PPh3)4 (15 mg, 0.013 mmol) was added to a suspension of <strong>[501945-71-7]2-benzo[b]thiophen-5-yl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane</strong> (Intermediate 3, 80.2 mg, 0.31 mmol), 1-[5-bromo-6-(6-methyl-pyridin-2-yl)-2,3-dihydro-imidazo[1,2-a]imidazol-1-yl]-ethanone (Intermediate 12, 83 mg, 0.26 mmol), 2CO3 (72 mg, 0.52 mmol) in toluene (4.5 mL) and EtOH (0.2 mL), and the mixture was stirred at 100 C under N2 for 16 hours. After cooling to room temperature, the mixture was filtered through celite, washed with CH2Cl2, and concentrated under a reduced pressure. The residue was purified by MPLC on NH silica gel eluting with CH2Cl2/hexane/EtOAc (3/l/0.5? 2/1/1) and recrysallization from CH2Cl2/hexane to obtain the coupled compound (18.2 mg, 19%) as a white solid.
  • 10
  • [ 501945-71-7 ]
  • [ 1624848-91-4 ]
  • [ 1624848-29-8 ]
  • 11
  • [ 3034-53-5 ]
  • [ 501945-71-7 ]
  • [ 1624849-00-8 ]
  • 12
  • [ 501945-71-7 ]
  • [ 1620098-61-4 ]
  • C30H29F6N5O5S2 [ No CAS ]
  • 13
  • [ 501945-71-7 ]
  • [ 14143-55-6 ]
  • methyl 4-amino-6-(benzo[b]thiophenyl-5-yl)-3,5-dichloropicolinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With bis-triphenylphosphine-palladium(II) chloride; cesium fluoride; In 1,4-dioxane; water; at 120℃; for 1h;Sealed tube; Inert atmosphere; Microwave irradiation; Example 4 Methyl 4-amino-6-(benzo[b]thiophenyl-5-yl)-3,5-dichloropicolinate (Compound No. 3.1) To a 5 mL microwave vial was added methyl 4-amino-3,5,6-trichloropicolinate (0.232 g, 0.909 mmol), <strong>[501945-71-7]2-(benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (0.260 g, 0.999 mmol), cesium fluoride (0.276 g, 1.817 mmol) and (PPh3)2PdCl2 (0.064 g, 0.091 mmol). The reaction vial was then sealed and placed under inert atmosphere. Subsequently, Dioxane (4.0 mL) and H2O (1.0 mL) were added and the reaction mixture was heated in a Biotage microwave at 120 C. for 60 min, with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (5 mL) and poured into brine solution. The layers were separated and the aqueous phase was extracted with ethyl acetate (3*10 mL). The organic extracts were combined, dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified using a Teledyne ISCO purification system with a gradient eluent system of ethyl acetate and hexanes. Further purification was performed, as needed, using a Teledyne ISCO reverse phase system with a gradient eluent system of acetonitrile and H2O to yield the title compound as a white solid.
  • 14
  • [ 501945-71-7 ]
  • [ 14143-55-6 ]
  • 4-amino-6-(benzo[b]thiophen-5-yl)-3,5-dichloropicolinic acid [ No CAS ]
  • 15
  • [ 76-09-5 ]
  • C10H11BO2S [ No CAS ]
  • [ 501945-71-7 ]
  • 16
  • [ 4923-87-9 ]
  • [ 501945-71-7 ]
  • 17
  • C14H20BNS [ No CAS ]
  • [ 501945-71-7 ]
  • 18
  • [ 4923-87-9 ]
  • [ 185990-03-8 ]
  • [ 501945-71-7 ]
  • 19
  • [ 501945-71-7 ]
  • 2-(benzo[b]thiophen-5-yl)-3-nitropyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
<Step 2> Synthesis of 2-(benzo[b]thiophen-5-yl)-3-nitropyridine 2-(benzo[b]thiophen-5-yl)-3-nitropyridine was obtained by performing the same procedure as in <Step 2> of Preparation Example 1, except that the <strong>[501945-71-7]2-(benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> obtained in <Step 1> was used instead of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole. 1H-NMR: delta 7.66 (d, 1H), 7.89 (d, 1H), 7.97 (d, 1H), 8.01 (d, 1H), 8.09 (m, 2H), 8.14 (s, 1H), 8.42 (d, 1H)
  • 20
  • [ 501945-71-7 ]
  • [ 1257307-01-9 ]
  • 3-(benzo[b]thiophen-5-yl)-6-fluoro-1-(phenylsulfonyl)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
500 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 90℃; for 1.5h;Inert atmosphere; Microwave irradiation; The mixture of 6-fluoro-3-iodo-1 -(phenylsulfonyl)-1 /-/-indole (Intermediate 1 , 401 mg, 1 .0 mmol) , 2-benzo[b]thiophen-5-yl-4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolane (423 mg, 1 .30 mmol, crude), and K3PO4 (636 mg, 3.0 mmol) in dioxane (12 mL) and water (3 mL) was bubbled with nitrogen for 5 mins. Pd(dppf)CI2 (73 mg, 0.1 mmol) was added and the mixture was bubbled with nitrogen for another 5 mins. The mixture was placed into microwave reactor and stirred at 90 C under nitrogen for 1 .5 h. The solvent was removed. The residue was dissolved in PE/EA (100 mL, PE/EA=3/1 ) and filtered through a short plug of silica. The solvent was removed to get 500 mg of the title compound as a yellow oil.
  • 21
  • [ 501945-71-7 ]
  • [ 696-62-8 ]
  • 2-(3-(4-methoxyphenyl)benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]
  • 22
  • [ 501945-71-7 ]
  • [ 696-62-8 ]
  • [ 1228187-45-8 ]
  • 23
  • [ 501945-71-7 ]
  • N-(3-amino-3-oxopropyl)-1-benzyl-5-iodo-N-(4-isopropoxybenzyl)-1H-pyrazole-4-carboxamide [ No CAS ]
  • N-(3-amino-3-oxopropyl)-5-(benzo[b]thiophen-5-yl)-1-benzyl-N-(4-isopropoxybenzyl)-1H-pyrazole-4-carboxamide [ No CAS ]
  • 24
  • [ 501945-71-7 ]
  • 5-[18F]fluorobenzo[b]thiophene [ No CAS ]
  • 25
  • [ 501945-71-7 ]
  • [ 37801-98-2 ]
  • 26
  • [ 501945-71-7 ]
  • C16H10N2S2 [ No CAS ]
  • 27
  • [ 501945-71-7 ]
  • 1-[1-(4,5-dibromothien-2-yl)cyclohexyl]pyrrolidine [ No CAS ]
  • 1-{1-[5-(benzo[b]thien-5-yl)-4-bromothien-2-yl]cyclohexyl}pyrrolidine [ No CAS ]
  • 28
  • [ 501945-71-7 ]
  • 1-[1-(4,5-dibromothien-2-yl)cyclohexyl]pyrrolidine [ No CAS ]
  • 5-{2-(benzo[b]thien-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thien-3-yl}-1H-indole [ No CAS ]
  • 29
  • [ 501945-71-7 ]
  • 1-[1-(4,5-dibromothien-2-yl)cyclohexyl]pyrrolidine [ No CAS ]
  • 1-{1-[4,5-bis(benzo[b]thien-5-yl)thien-2-yl]cyclohexyl}pyrrolidine [ No CAS ]
  • 30
  • [ 501945-71-7 ]
  • 5-{3-bromo-5-[1-(pyrrolidin-1-yl)cyclohexyl]thien-2-yl}-1H-indole [ No CAS ]
  • 5-{3-(benzo[b]thien-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thien-2-yl}-1H-indole [ No CAS ]
  • 31
  • [ 501945-71-7 ]
  • [ 1663-39-4 ]
  • [ 2969-81-5 ]
  • diethyl 4,4'-(5-(3-(tert-butoxy)-3-oxoprop-1-en-1-yl)benzo[b]thiophene-4,6-diyl)(E)-dibutyrate [ No CAS ]
  • 33
  • [ 501945-71-7 ]
  • 4-(4-bromo-2-(2-methyl-4-(methylsulfonyl)phenyl)-1H-imidazol-5-yl)pyridine [ No CAS ]
  • 4-(4-(benzo[b]thiophen-5-yl)-2-(2-methyl-4-(methylsulfonyl)-phenyl)-1H-imidazol-5-yl)pyridine [ No CAS ]
  • 34
  • [ 501945-71-7 ]
  • [ 90-14-2 ]
  • [ 80-48-8 ]
  • 5-(2-methylnaphthalen-1-yl)benzo[b]thiophene [ No CAS ]
 

Historical Records

Categories

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[ 501945-71-7 ]

Organoborons

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