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Chemical Structure| 868066-91-5 Chemical Structure| 868066-91-5

Structure of 868066-91-5

Chemical Structure| 868066-91-5

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Product Details of [ 868066-91-5 ]

CAS No. :868066-91-5
Formula : C9H8BrNO
M.W : 226.07
SMILES Code : O=C1N(C)CC2=C1C=CC(Br)=C2
MDL No. :MFCD12755780
InChI Key :WRFZBWHXIGUNLQ-UHFFFAOYSA-N
Pubchem ID :23158169

Safety of [ 868066-91-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 868066-91-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 54.0
TPSA ?

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

20.31 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.14
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

1.65
Log Po/w (WLOGP)?

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

1.5
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.

2.17
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

2.39
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.97

Water Solubility

Log S (ESOL):?

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

-2.65
Solubility 0.505 mg/ml ; 0.00223 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-1.69
Solubility 4.62 mg/ml ; 0.0204 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

-3.42
Solubility 0.0859 mg/ml ; 0.00038 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

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

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

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

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.

-6.51 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

0.0 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)

1.49

Application In Synthesis of [ 868066-91-5 ]

* 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 [ 868066-91-5 ]

[ 868066-91-5 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 888030-79-3 ]
  • (5-bromo-3<i>H</i>-isobenzofuran-1-ylidene)-methyl-amine [ No CAS ]
  • [ 868066-91-5 ]
  • 3
  • [ 888030-79-3 ]
  • [ 868066-91-5 ]
YieldReaction ConditionsOperation in experiment
57.3% A 150 mL sealed tube was charged with 4-bromo-2- (hydroxymethyl) -N-tnethylbenzamide (3.34 g, 13.7 mmol) and 1,3- dimethylimidazolidin-2-one (40.4 ml, 369 mmol). The solution was cooled to 00C and Isopropylmagnesium chloride (15.3 ml, 30.5 mmol) was added slowly. The tube was capped and the reaction mixture was stirred at room temperature for 30 minutes. This was recooled to 00C and N,N,N,N- tetramethylphosphorodiamidoyl chloride (2.64 ml, 17.8 mmol) was added in one portion; this mixture was stirred at room temperature for 4 hours. The tube was placed in a 150°C oil bath for 1 hour. The mixture was then diluted with EtOAc (100 mL) , then washed with IM aqueous HCl . The aqueous layer was extracted with ethyl acetate (3 x 100 mL) and then the combined organics were washed with water (100 mL) and brine (100 mL) , dried with MgSO4, filtered, then concentrated to give a yellow oil . This was purified by column chromatography, eluting with 1 - 4percent MeOH/DCM to give 5-bromo-2-methylisoindolin-l-one (1.774 g, 57.3percent yield) as a yellow solid.
  • 4
  • [ 868066-91-5 ]
  • [ 73183-34-3 ]
  • [ 1002309-19-4 ]
YieldReaction ConditionsOperation in experiment
89% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 85℃;Inert atmosphere; [00532] Intermediate Sic: 2-methyl-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yI)isoindolin-1-one[00533] A round bottomed flask containing bis(pinacolato)diboron (354mg, 1 .3gmmol) and KOAc (326mg, 3.32mmol) in 1 ,4-dioxane (6.5mL) was evacuated/backfilled with nitrogen. Pd(dppt)C12.CH2CI2 (54mg, 0.O7mmol) was added and the flask was evacuated/backfilled with nitrogen again. The reaction mixture was then stirred and heated at 85 C overnight. After this timethe mixture was cooled to room temperature, filtered through a plug of celite and the solid was washed with EtOAc. The filtrate was concentrated and the residue purified by column chromatography using an eluent of 0-100% EtOAc in heptane to give 2-methyl-5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (324mg,1.lgmmol, 89% yield) as a brown solid.1H NMR (CDCI3, 400MHz) O/ppm: 7.92 (1H, dd, J= 7.6Hz, 0.4Hz), 7.90-7.89 (1H, m), 7.85 (1H, dd, J 7.6Hz, 0.4Hz), 4.39 (2H, 5), 3.23 (3H, 5), 1.38 (12H, 5).MS Method 3: RT: 3.61 mi m/z 274.1 [M+H]
With potassium acetate; XPhos;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 85℃; for 22h; In a sealable tube was combined Pd2dba3 (0.0270 g, 0.0295 mmol), 2- (dicyclohexylphosphino) -2' , 4', 6'- tri-i-propyl-1, 1' -biphenyl (0.0563 g, 0.118 mmol) , 4 , 4, 5, 5- tetramethyl-2- (4,4, 5 , 5-tetramethyl-l, 3 , 2-dioxaborolan-2-yl) - 1, 3, 2-dioxaborolane (0.450 g, 1.77 mmol), 5-bromo-2- <n="113"/>methylisoindolin-1-one (see Tsuritani, T., et al Synlett 2006, 5 801-803} (0.267 g, 1.18 mmol) , potassium acetate (0.232 g, 2.36 mmol) and 2 mL dioxane . The mixture was blanketed with N2, sealed and heated at 80 C for 22 h. The mixture was allowed to cool to rt then diluted with EtOAc, and the organic layer washed with water, sat. NaHCO3, then dried over Na2SO4, filtered and evaporated. The residue was purified via flash chromatography using a EtOAc in CH2Cl2 gradient. The title compound was collected as a tan solid.
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 100℃; for 4h;Inert atmosphere of nitrogen; To a solution of 5-bromo-2-methylisoindolin-l-one (Example 31, step (i), 60.4 g) in dioxane (2 L) was added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2-dioxaborolane) (67.8 g), potassium acetate (65.4 g) and Pd(dppf)Cl2 (6 g) under an atmosphere of nitrogen. The mixture was heated to 1000C and stirred for 4 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated and the crude product was purified by chromatography on silica eluting with petroleum ether / ethyl acetate (6:1 to 2: 1) to afford the sub-titled compound (72 g).1H NMR (400 MHz, CDCl3): delta 7.89-7.88 (m, 2H), 7.83-7.81 (m, IH), 4.35 (s, 2H), 3.19 (s, 3H), 10.34 (s, 12H).
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl acetamide; at 100℃;Inert atmosphere; Step B: 2-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)isoindolin-l-one [0236] 5-Bromo-2-methylisoindolin-l-one (0.112 g, 0.495 mmol), bis(pinacolato)diboron (0.189 g, 0.743 mmol), potassium acetate (0.146 g, 1.486 mmol), and PdCl2(dppf)CH2Cl2 adduct (0.020 g, 0.025 mmol) were suspended in DMA (1.0 mL). The mixture was degassed with N2 and heated in a sand bath at 100C overnight. The reaction mixture was subsequently cooled, diluted with EtOAc (10 mL), and passed through a syringe filter. The filtrate was diluted with water (10 mL) and the layers were separated. The aqueous layer was washed with EtOAc (2 x 5 mL). The organic layers were combined and concentrated in vacuo to give the title compound as a brown residue, which was used without further purification.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90℃;Inert atmosphere; In a vial was combined <strong>[868066-91-5]5-bromo-2-methylisoindolin-1-one</strong> (226 mg, 1.00 mmol) [Ark Pharm cat AK-37748], 4,4,5,5,4?,4?,5?,5?-octamethyl-[2,2?]bi[[1,3,2]dioxaborolanyl] (0.533 g, 2.10 mmol), potassium acetate (294 mg, 3.00 mmol), 1,4-dioxane (5.0 mL), and [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (36.6 mg, 0.050 mmol). The vial was de-gassed by bubbling nitrogen through the solvent for 5 minutes then heated to 90 C. overnight. The mixture was allowed to cool to room temperature and was then filtered using a syringe filter. The filtrate was then concentrated under reduced pressure and used without further purification. LC-MS calculated for C15H21BNO3(M+H)+: m/z=274.2. found 274.1.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 100℃; for 5h; 5-Bromo-2-methylisoindolin-1-one synthesized in step 1 (Formula 5-2, 2.1 g, 9.20 mmol), potassium acetate (2.26 g, 23 mmol, 2.5 eq), Pd (dppf) Cl 2 -CH 2 Cl 2 (0.225 g, 0.28 mmol, 0.03 eq) and B 2 Pin 2 (2.34 g, 9.20 mmol, 1 eq) were dissolved in 1,4-dioxane (20 ml). The temperature was raised to 100 ° C and the reaction mixture was stirred for 5 hours.After completion of the reaction, the mixture was extracted with dichloromethane. The organic layer was washed sequentially with H 2 O and brine, then dried over anhydrous MgSO 4,The solvent was removed under reduced pressure.Thereafter, the reaction mixture was separated and purified by MPLC (hexane / ethyl acetate; 70:30) to obtain the target compound (Formula 5-3).

  • 5
  • [ 888030-82-8 ]
  • [ 868066-91-5 ]
  • 6
  • [ 64169-34-2 ]
  • [ 868066-91-5 ]
  • 7
  • [ 124-40-3 ]
  • [ 78471-43-9 ]
  • [ 868066-91-5 ]
YieldReaction ConditionsOperation in experiment
In methanol; for 18h;Heating; Reflux; A solution of methyl 4-bromo-2-(bromomethyl)benzoate (410 mmol) in MeNH2ZMeOH (1500 niL) was heated to reflux and stirred for 18 h. The reaction mixture was concentrated and the residue was purified by chromatography on silica eluting with petroleum ether / ethyl acetate (6:1 to 3:1) to afford the sub-titled compound (48.5 g).1H NMR (400 MHz, CDCl3): delta 7.63-7.61 (m, IH), 7.53-7.54 (m, 2H), 4.29 (s, 2H), 3.12 (s, 3H).
  • 8
  • [ 74-89-5 ]
  • [ 78471-43-9 ]
  • [ 868066-91-5 ]
YieldReaction ConditionsOperation in experiment
71% In tetrahydrofuran; at 50℃;Sealed tube; [00530] Intermediate 51 b: 5-bromo-2-methyl-isoindolin-1 -one[00531] To a reaction tube containing methyl 4-bromo-2-(bromomethyl)benzoate (1 .2g, 3.gmmol) was added methylamine (2.OM in THF, lOmL, 2Ommol). The tube was sealed and the mixture was stirred and heated at 50 C overnight. The mixture was then cooled to room temperature, filtered and the precipitate washed with THF. The filtrate was concentrated in vacuo and the residue waspurified by column chromatography using an eluent of 0-100% EtOAc in heptane to give 5-bromo-2- methyl-isoindolin-1-one (623mg, 2.7Smmol, 71% yield) as a white solid.1H NMR (CDCI3, 400MHz) O/ppm: 7.73-7.68 (1H, m), 7.64-7.56 (2H, m), 4.36 (2H, 5), 3.19 (3H, 5). MS Method 3: RT: 3.18 mi m/z226.0/228.0 [M+H]
68% With triethylamine; In tetrahydrofuran; at 100℃; for 12h;Sealed tube; Synthesis of 5-bromo-2-methylisoindolin-1-one (2) A mixture of methyl 4-bromo-2-(bromomethyl)benzoate (1, 1 g, 3.26 mmol), 2 M methylamine in tetrahydrofuran (1.95 mL, 3.9 mmol) and triethylamine (0.9 mL, 6.52 mmol) was heated at 100 C. for 12 h in a sealed tube. After completion of the reaction, the mixture was concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate and washed with water. The organic was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was triturated with hexane to afford 5-bromo-2-methylisoindolin-1-one (2). Yield: 0.5 g, 68%; MS (ESI) m/z 226, 228 [M+1]+.
0.112 g In methanol; at 90℃; for 24h; Step A: 5-bromo-2-methylisoindolin-l-one [0234] Methyl 4-bromo-2-(bromomethyl)benzoate (0.153 g, 0.497 mmol) was suspended in methanamine (2M solution in MeOH, 2.484 mL, 4.97 mmol) and the mixture was heated to reflux (90C) for 24 hours. The reaction mixture was cooled, concentrated in vacuo, and dried under high vacuum to give the title compound (0.112 g). lU NMR (500 MHz, CDC13) delta ppm 3.19 (s, 3 H), 4.36 (s, 2 H), 7.57 - 7.62 (m, 2 H), 7.70 (d, J=8.30 Hz, 1 H); ESI-MS m/z [M+H]+ 226.3.
In methanol; ethanol;Reflux; To a solution of compound 1a (15 g, 50 mmol) in methanol (150 ml) was added methylamine (25 ml, 33% inethanol), and the reaction was refluxed overnight. After the organic solvent was drained off, the mixture was separatedby silica gel column chromatography (PE/EA= 3:1) to provide a yellow oily compound 1b.HNMR(CDCl3),7.5-7.7(m,3H),4.3(s,2H),3.1(s,3H).MS(ESI)m/z:225.9(M+H)+.
for 18h;Reflux; Methyl 4-bromo-2- (bromomethyl) benzoate (Formula 5-1, 2.5 g, 8.12 mmol) was dissolved in 2M methanamine (122 ml, 244 mmol, 30 eq) and then stirred at reflux for 18 hours. After completion of the reaction, Extracted with dichloromethane. The organic layer was washed with H 2 O, dried over anhydrous MgSO 4, and the solvent was removed under reduced pressure.Thereafter, the reaction mixture was separated and purified by MPLC (hexane / ethyl acetate; 70:30) to obtain a target compound (Formula 5-2).

  • 12
  • [ 868066-91-5 ]
  • [ 1567837-79-9 ]
  • 13
  • [ 868066-91-5 ]
  • 2,4-difluoro-N-(5-(5-(2-methyl-1-oxoisoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)benzenesulfonamide, sodium salt [ No CAS ]
  • 14
  • [ 868066-91-5 ]
  • [ 1567836-81-0 ]
  • 15
  • [ 868066-91-5 ]
  • [ 1567836-94-5 ]
  • 16
  • [ 868066-91-5 ]
  • [ 1567837-01-7 ]
  • 17
  • [ 868066-91-5 ]
  • [ 6165-68-0 ]
  • [ 1567836-35-4 ]
YieldReaction ConditionsOperation in experiment
97% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; General procedure: 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 solution of 2 M Na2CO3 (3 mL) and Pd(dppf)C12 (94 mg, 0.12 mmol) were added and the entire mixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30 mmol) was added and reflux continued under N2 overnight. Upon cooling, themixture was diluted with water (100 mL) and extracted with CH2C12 (6x50 mL). The combined organic fractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure to give a crude solid which was purified by flash column chromatography on silica gel (EtOAc as eluant). The title compound was isolated as a light-brown solid (510 mg, 97percent). ?H NMR [400 MHz, (CD3)2S0] 8 7.87 (s, 1 H), 7.77 (dd, J? 7.9, 1.6 Hz,1 H), 7.67 (dd, J 7.9, 0.3 Hz, 1 H), 7.61-7.66 (m, 2 H), 7.18 (dd, J 5.0, 1.4 Hz, 1 H),4.49 (s, 2 H), 3.08 (s, 3 H). LRMS (APCI) calcd for C13H,2NOS 230 (MH), found 230.
97% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; 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). 1H NMR[400 MHz, (CD3)2SO] delta 7.87 (s, 1 H), 7.77 (dd, J = 7.9, 1.6 Hz, 1 H), 7.67 (dd, J = 7.9, 0.3Hz, 1 H), 7.61-7.66 (m, 2 H), 7.18 (dd, J = 5.0, 1.4 Hz, 1 H), 4.49 (s, 2 H), 3.08 (s, 3 H).LRMS (APCI+) calcd for C13H12NOS 230 (MH+), found 230.
  • 18
  • [ 552330-86-6 ]
  • [ 74-88-4 ]
  • [ 868066-91-5 ]
YieldReaction ConditionsOperation in experiment
80% General procedure: Bromoisoindolin-1-one (2.0 g, 9.43 mmol) was dissolved with warming in DMF (150 mL),then cooled to 0°C. NaH (415 mg, 10.4 mmol) was added and the mixture stirred under N2 at 0°C for 0.5 h. Methyl iodide (0.65 mL, 10.4 mmol) was added dropwise and the reaction allowed to warm to room temperature and stir for another I h. A small quantity of water was added to quench the reaction then the DMF removed under reduced pressure to give an oily yellow residue which was dissolved in EtOAc (150 mL). This solution waswashed with water (3x100 mL), brine (100 mL) and dried (Na2SO4)., Removal of the solvent under reduced pressure gave a solid which was purified by filtration through a plug of silica gel (10percent acetone/CH2C12 as eluant). The title compound was isolated as a very pale yellow crystalline solid (1.64 g, 80percent). ? H NMR [400 MHz, (CD3)2S0] oe 7.85 (dd, J= 1.5, 0.6 Hz, 1 H), 7.66 (dd, J= 8.0, 1.7 Hz, 1 H), 7.59 (d, J? 8.0 Hz, I H), 4.46 (s,2 H), 3.05 (s, 3 H). LRMS (APCI) calcd for C9H8BrNO 226, 228 (MH), found 226, 228.
61.9% 5-Bromo-2-methylisoindolin-1-oneTo a solution of 5-bromoisoindolin-1-one (2500 mg, 11.79 mmol) in DMF (20 mL) under nitrogen, at 0 °C, was added NaH (566 mg, 14.15 mmol) and the mixture was stirred for 30 min. After which, Mel (0.885 mL, 14.15 mmol) was added dropwise and the mixture was stirred at 0 °C for 2 h. The reaction was quenched with sat. aqueous NH4CI, and extracted with EtOAc (3 x 30 mL). The organic layer was washed with brine, dried and concentrated to afford 5-bromo-2-methylisoindolin-1-one (2500 mg, 7.30 mmol, 61.9 percent yield). LC-MS: m/z 226 (M+H)+1.02 min (ret. time).
  • 19
  • [ 78471-43-9 ]
  • [ 868066-91-5 ]
  • 20
  • [ 68837-59-2 ]
  • [ 868066-91-5 ]
  • 22
  • [ 868066-91-5 ]
  • [ 1161499-39-3 ]
  • [ 1579996-77-2 ]
  • 23
  • [ 868066-91-5 ]
  • [ 1579996-83-0 ]
  • C23H27N3O4 [ No CAS ]
  • 24
  • [ 868066-91-5 ]
  • [ 1254319-24-8 ]
  • [ 1254319-52-2 ]
  • 25
  • [ 868066-91-5 ]
  • tert-butyl (2S)-2-[[4-[(3-cyano-1H-indol-5-yl)oxy]phenyl]carbamoyl]pyrrolidine-1-carboxylate [ No CAS ]
  • C34H33N5O5 [ No CAS ]
  • 26
  • [ 868066-91-5 ]
  • tert-butyl (2S)-2-[[4-[(3-cyano-1H-indol-5-yl)oxy]phenyl]carbamoyl]pyrrolidine-1-carboxylate [ No CAS ]
  • (2S)-N-[4-[3-cyano-1-(2-methyl-1-oxoisoindolin-5-yl)indol-5-yl]oxyphenyl]pyrrolidine-2-carboxamide [ No CAS ]
  • 27
  • [ 868066-91-5 ]
  • C31H34N2O6S [ No CAS ]
  • 28
  • [ 868066-91-5 ]
  • 3-(2-methyl-1-oxoisoindolin-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid [ No CAS ]
  • 29
  • [ 868066-91-5 ]
  • [ 140-88-5 ]
  • (E)-ethyl 3-(2-methyl-1-oxoisoindolin-5-yl)acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
49.6% With palladium diacetate; triethylamine; tris-(o-tolyl)phosphine; In acetonitrile; at 80℃; for 3h; (E)-Ethyl 3-(2-methyl-1-oxoisoindolin-5-yl)acrylateA mixture of tri-o-tolylphosphine (0.242 g, 0.796 mmol), ethyl acrylate (1.594 g, 15.92 mmol), <strong>[868066-91-5]5-bromo-2-methylisoindolin-1-one</strong> (1.8 g, 7.96 mmol), Pd(OAc)2(0.089 g, 0.398 mmol), and TEA (2.220 mL, 15.92 mmol) in CH3CN (25.0 mL) was stirred at 80 °C for 3 h. The reaction was filtered and concentrated and the residue was purified by flash column chromatography eluting with petroleum ether/EtOAc (1/5), to afford (E)-ethyl 3-(2- methyl-1-oxoisoindolin-5-yl)acrylate (1.02 g, 3.95 mmol, 49.6 percent yield). LC-MS: m/z 247 (M+H)+1.50 min (ret. time).
  • 30
  • [ 868066-91-5 ]
  • 2-(2-methyl-1-oxo-isoindolin-5-yl)acetic acid [ No CAS ]
  • 31
  • [ 868066-91-5 ]
  • [ 100939-90-0 ]
  • 5-(4-(3-chlorobenzoyl)piperazin-1-yl)-2-methylisoindolin-1-one [ No CAS ]
  • 32
  • [ 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).
  • 33
  • [ 827614-64-2 ]
  • [ 868066-91-5 ]
  • [ 1567838-03-2 ]
YieldReaction ConditionsOperation in experiment
68% 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).
  • 34
  • [ 868066-91-5 ]
  • 5-(5-iodofuran-2-yl)-2-methylisoindolin-1-one [ No CAS ]
  • 35
  • [ 868066-91-5 ]
  • 5-(5-(5-aminopyridin-3-yl)furan-2-yl)-2-methylisoindolin-1-one [ No CAS ]
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Categories

Related Functional Groups of
[ 868066-91-5 ]

Bromides

Chemical Structure| 1254319-51-1

A153276 [1254319-51-1]

6-Bromo-2-methylisoindolin-1-one

Similarity: 1.00

Chemical Structure| 153171-22-3

A916326 [153171-22-3]

2-(4-Bromobenzyl)isoindoline-1,3-dione

Similarity: 0.98

Chemical Structure| 6941-75-9

A292220 [6941-75-9]

5-Bromoisoindoline-1,3-dione

Similarity: 0.95

Chemical Structure| 675109-26-9

A345051 [675109-26-9]

6-Bromoisoindolin-1-one

Similarity: 0.95

Chemical Structure| 435273-55-5

A342403 [435273-55-5]

4-Bromo-2-methylisoindolin-1-one

Similarity: 0.93

Amides

Chemical Structure| 1254319-51-1

A153276 [1254319-51-1]

6-Bromo-2-methylisoindolin-1-one

Similarity: 1.00

Chemical Structure| 153171-22-3

A916326 [153171-22-3]

2-(4-Bromobenzyl)isoindoline-1,3-dione

Similarity: 0.98

Chemical Structure| 6941-75-9

A292220 [6941-75-9]

5-Bromoisoindoline-1,3-dione

Similarity: 0.95

Chemical Structure| 675109-26-9

A345051 [675109-26-9]

6-Bromoisoindolin-1-one

Similarity: 0.95

Chemical Structure| 435273-55-5

A342403 [435273-55-5]

4-Bromo-2-methylisoindolin-1-one

Similarity: 0.93

Related Parent Nucleus of
[ 868066-91-5 ]

Indolines

Chemical Structure| 1254319-51-1

A153276 [1254319-51-1]

6-Bromo-2-methylisoindolin-1-one

Similarity: 1.00

Chemical Structure| 153171-22-3

A916326 [153171-22-3]

2-(4-Bromobenzyl)isoindoline-1,3-dione

Similarity: 0.98

Chemical Structure| 6941-75-9

A292220 [6941-75-9]

5-Bromoisoindoline-1,3-dione

Similarity: 0.95

Chemical Structure| 675109-26-9

A345051 [675109-26-9]

6-Bromoisoindolin-1-one

Similarity: 0.95

Chemical Structure| 435273-55-5

A342403 [435273-55-5]

4-Bromo-2-methylisoindolin-1-one

Similarity: 0.93