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Chemical Structure| 2181-42-2 Chemical Structure| 2181-42-2

Structure of 2181-42-2

Chemical Structure| 2181-42-2

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Product Details of [ 2181-42-2 ]

CAS No. :2181-42-2
Formula : C3H9IS
M.W : 204.07
SMILES Code : C[S+](C)C.[I-]
MDL No. :MFCD00011632
InChI Key :VFJYIHQDILEQNR-UHFFFAOYSA-M
Pubchem ID :75127

Safety of [ 2181-42-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Computational Chemistry of [ 2181-42-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 5
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 38.98
TPSA ?

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

25.3 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

1.75
Log Po/w (WLOGP)?

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

-2.5
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.

2.23
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

-0.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.15

Water Solubility

Log S (ESOL):?

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

-2.21
Solubility 1.26 mg/ml ; 0.0062 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.

-1.9
Solubility 2.58 mg/ml ; 0.0126 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

-1.03
Solubility 19.1 mg/ml ; 0.0935 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

Low
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.

-6.3 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

2.0 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)

2.46

Application In Synthesis of [ 2181-42-2 ]

* 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 [ 2181-42-2 ]

[ 2181-42-2 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 4903-09-7 ]
  • [ 2181-42-2 ]
  • 2-(3-chloro-4-methoxyphenyl)oxirane [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With potassium hydroxide; In dimethyl sulfoxide; at 40℃; for 7h;Inert atmosphere; To a mixture of <strong>[4903-09-7]3-chloro-4-methoxybenzaldehyde</strong> (2.00 g,11.7 mmol) and trimethylsulfonium iodide (3.35 g, 16.4 mmol) inDMSO (12 mL) was added potassium hydroxide (0.920 g,16.4 mmol). After stirring at 40 C for 7 h, the reaction mixturewas diluted with EtOAc (50 mL) and washed with H2O (100 mL).The aqueous layer was extracted with EtOAc (50 mL). To the combinedorganic layer was added toluene (100 mL), and the wholewas washed with H2O (100 mL), dried over Na2SO4, filtered andconcentrated in vacuo to give 2.25 g (quant.) of the title compoundas a pale yellow oil. The obtained compound 12a was used in thenext reaction without further purification. 1H NMR (300 MHz,CDCl3) d: 2.77 (1H, dd, J = 5.3, 2.6 Hz), 3.13 (1H, dd, J = 5.3,4.0 Hz), 3.80 (1H, dd, J = 4.0, 2.6 Hz), 3.90 (3H, s), 6.90 (1H, d,J = 8.4 Hz), 7.16 (1H, dd, J = 8.5, 2.1 Hz), 7.28 (1H, d, J = 2.2 Hz).
  • 2
  • [ 13726-16-4 ]
  • [ 2181-42-2 ]
  • 2-(4-Chloro-3-methoxy-phenyl)-oxirane [ No CAS ]
  • 4
  • [ 32024-15-0 ]
  • [ 2181-42-2 ]
  • 2-(3-Iodo-4,5-dimethoxy-phenyl)-oxirane [ No CAS ]
  • 5
  • [ 14615-72-6 ]
  • [ 2181-42-2 ]
  • [ 50841-47-9 ]
  • 6
  • [ 51179-18-1 ]
  • [ 2181-42-2 ]
  • [ 484-29-7 ]
  • [ 827303-64-0 ]
  • 7
  • [ 31739-56-7 ]
  • [ 2181-42-2 ]
  • [ 1001053-74-2 ]
  • 8
  • [ 17159-79-4 ]
  • [ 2181-42-2 ]
  • [ 171361-65-2 ]
YieldReaction ConditionsOperation in experiment
With 2,8,9-tris(2-methylpropyl)-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane; In acetonitrile; at 0 - 20℃; for 1.5h;Product distribution / selectivity; Procedure 9b; A mixture of 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (1.14 ml, 3.94 mmol) and acetonitrile (15 ml) was added to a stirred suspension of trimethylsulphonium iodide (0.81 g, 3.97 mmol) and ethyl 4-oxocyclohexanecarboxylate (0.563 g, 3.31 mmol) at 0 0C. The mixture was stirred at 0 0C for 30 minutes then allowed to warm to room temperature and stirred for a further 1 hour. The reaction mixture was concentrated under reduced pressure then diluted with diethyl ether. The resulting suspension was stirred for 30 minutes then filtered and the filter cake was washed with more diethyl ether. The combined ethereal phases were concentrated under reduced pressure and the residue was chromatographed on SiO2 (Biotage 25M column) eluting with a gradient of 5%-15% EtOAc/cyclohexane to give a -60:40, trans:cis mixture of the title compound as a colourless oil (250 mg); <n="30"/>1 H NMR (400 MHz, CDCI3): delta 4.16 (2H both isomers, q), 2.65 (2H trans isomer, s), 2.62 (2H cis isomer, s), 2.35-2.48 (1 H both isomers, m), 1.68-2.14 (6H both isomers, m), 1.37- 1.52 (2H both isomers, m), 1.27 (3H both isomers, t).
  • 9
  • [ 2923-66-2 ]
  • [ 2181-42-2 ]
  • [ 1147939-72-7 ]
YieldReaction ConditionsOperation in experiment
Example 24 Preparation of 2-(3-chloro-4-fluorophenyl)-2-methyloxirane[0389] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of l-(3-chloro-4-fluorophenyl)ethanone (1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to obtain the product
Example 28A [0445] DMSO was added to NaH (1 equiv) and heated to 65 0C for 1 h. THF was added at same temperature and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1 equiv) was added and stirred for 10 min after which the solution of l-(3-chloro-4-fluorophenyl)ethanone (1 equiv) in THF was added dropwise. After complete addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted with diethyl ether (4x50 mL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get the product.
  • 10
  • [ 885167-81-7 ]
  • [ 2181-42-2 ]
  • [ 1400997-49-0 ]
YieldReaction ConditionsOperation in experiment
26% EXAMPLE 120(RS)-N-(5-Bromopyridin-2-yl)-3-methyl-5-(morpholin-2-yl)pyridin-2-aminea) (RS)-2-Bromo-3-methyl-5-(oxiran-2-yl)pyridineTo a stirred suspension of sodium hydride (1.01 g) in THF (20 ml) was added dropwise over 5 min a solution of trimethylsulfonium iodide (4.69 g) in DMSO (20 ml). The reaction mixture was stirred for 5 min and then cooled to 0 C. A solution of <strong>[885167-81-7]6-bromo-5-methylnicotinaldehyde</strong> (4.6 g, CAS 885167-81-7) in THF (15 ml) was added dropwise. The reaction mixture was stirred at 0 C. for 30 min and then at room temperature overnight. The mixture was then poured into EtOAc/Et2O (1:1) and washed with saturated brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes) to afford (RS)-2-bromo-3-methyl-5-(oxiran-2-yl)pyridine (1.26 g, 26%) as a colourless oil. MS (ISP): 216.1 ([{81 Br}M+H]+), 214.1 ([{79Br}M+H]+).
26% To a stirred suspension of sodium hydride (1.01 g) in THF (20 ml) was added dropwise over 5 min a solution of trimethylsulfonium iodide (4.69 g) in DMSO (20 ml). The reaction mixture was stirred for 5 minand then cooled to 0 C. A solution of <strong>[885167-81-7]6-bromo-5-methylnicotinaldehyde</strong> (4.6 g, CAS 885167-81-7) in THF (15 ml) was added dropwise. The reaction mixture was stirred at 0 C for 30 min and then at room temperature overnight. The mixture was then poured into EtOAc/Et20 (1: 1) and washed with saturated brine. The organic layer was dried over Na2S04 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes) to afford (RS)-2-bromo-3-methyl-5-(oxiran-2- yl)pyridine (1.26 g, 26%) as a colourless oil. MS (ISP): 216.1 ([{ 81Br}M+H]+), 214.1([{79Br}M+H]+).
  • 11
  • [ 21962-49-2 ]
  • [ 2181-42-2 ]
  • [ 1255207-21-6 ]
YieldReaction ConditionsOperation in experiment
To a cool solution of NaH (0.16 g, 3.9 mmol) inTHF (40 ml) was added dropwise a solution of trimethylsulfonium iodide (0.9 1 g, 4.5 mmol) inDMSO (20 ml). The resulting mixture was stirred at 0 under N2 for 20 min. The solution of <strong>[21962-49-2]4-formyl-2-methoxybenzonitrile</strong> (0.60 g, 3.7 mmol) in THF (20 ml) was added. The resultingreaction mixture was stirred at O c under N2 for 1 hr, and then it was warmed gradually to room temperature and stirred at that temperature for 12 hr. The starting material was consumed as indicated by TLC (25% ethyl acetatelhexanes). The reaction mixture was cooled to O c and quenched by drop-wise addition of water. The mixture was extracted with ethyl acetate (2 x 70 mL). The combined organie layers were washed with water, brine, then dried (Mg504) andfiltered. The filtrate was concentrated in yacuo. The residue was purified via column chromatography (silica gel, 10-30% EtOAc-hexanes) to afford 2-methoxy-4-(oxiran-2- yl)benzonitrile. lH NMR (CDC13, 500 MHz) 7.57 (d, J= 8Hz, 1H), 6.99 (dd, J= 1.1 Hz, J=1.2 Hz, 1H), 6.89 (s, 1H), 3.97 (s, 3H), 3.94-3.92 (m, 1H), 3.22 (dd, J= 5.2, Hz, J= 4.1 Hz, 1H),2.77 (J = 2.5 Hz, 1H); LC/MS (IE, miz) 176.33 [M + 11+
General procedure: To a cool solution of NaH (0.16 g, 3.9 mmol) in THF (40 mL) wasadded dropwise a solution of trimethylsulfonium iodide (0.91 g, 4.5 mmol) in DMSO (20 mL). The resulting mixturewas stirred at 0C under N2 for 20 min. A solution of <strong>[21962-49-2]4-formyl-2-methoxybenzonitrile</strong> (0.60 g, 3.72 mmol) in THF(20 mL) was added. The resulting reaction mixture was stirred at 0C under N2 for 1 hr, and then it was warmedgradually to room temperature and stirred at that temperature for 12 hr. The starting material was consumed asindicated by TLC (25%ethyl acetate/hexanes). The reaction mixture was cooled to 0C and quenched with dropwiseaddition of water. The mixture was extracted with ethyl acetate (2 x 70 mL). The combined organic layers werewashed with water, brine, then dried (MgSO4) and filtered. The filtrate was concentrated in vacuo. The residue was purified via column chromatography (silica gel, 10-30% EtOAc-hexanes) to afford 2-methoxy-4-(oxiran-2-yl)benzonitrile:1H NMR (CDCl3, 500 MHz) δ 7.57 (d, J = 8 Hz, 1H), 6.99 (dd, J = 1.1 Hz, J = 1.2 Hz, 1H), 6.89 (s, 1H),3.97 (s, 3H), 3.94-3.92 (m, 1H), 3.22 (dd, J = 5.2, Hz, J = 4.1 Hz, 1H), 2.77 (d, J = 2.5 Hz, 1H); LC/MS: (IE, m/z) [M+ 1]+ = 176.33.
  • 12
  • [ 22929-52-8 ]
  • [ 2181-42-2 ]
  • [ 185-61-5 ]
YieldReaction ConditionsOperation in experiment
1% Step 1. Synthesis of Intermediate 5-2. To a mixture of trimethylsulfoxonium iodide (28.3 g, 139 mmol) in DMSO (60 mL) was added NaH (5.55 g, 60percent in mineral oil, 139 mmol) in portions at 5 °C under N2 and the mixture was stirred at 5 °C for 30 mins. Dihydrofuran-3(2H)- one (10 g, 116 mmol) in DMSO (40 mL) was added dropwise while maintaining the temperature below 15 °C and the resulting mixture was stirred at 15 °C for 20 hrs. The reaction was quenched at 10 °C with water (200 mL) and extracted with MTBE (2 x 200 mL). The combined organic phases were washed with brine (200 mL), dried over Na2SO4, filtered and concentrated and the residue was purified by silica gel chromatography (0percent~40percent EtOAc in PE) to afford Intermediate 5-2 (100 mg, 1percent) as a colorless oil. (0326) 1H NMR (400 MHz, CDCl3) delta 4.12-3.93 (m, 3H), 3.68 (d, J = 10.4Hz, 1H), 3.05 (d, J = 4.4Hz, 1H), 2.96 (d, J = 4.4Hz, 1H), 2.37-2.25 (m, 1H), 2.02-1.92 (m, 1H).
  • 13
  • [ 359-41-1 ]
  • [ 67442-07-3 ]
  • [ 2181-42-2 ]
  • [ 1388149-59-4 ]
YieldReaction ConditionsOperation in experiment
49% To a solution of trimethylsulfonium iodide (41.51 g, 203.9 mmol) in THF (335.3 mL)at -30 °C was added lithium bis(trimethylsilyl)amide (1M in heptane, 203.9 mL, 203.9mmol) portionwise over 45 mills. After stirring for 30 mins, 3,3,3-trifluoro-1,2- epoxypropane (14 g, 124.9 mmol) was added at -20 °C over 15 mill, and the mixture was allowed to warm to RT and stirred for 3 h and 10 mm. The slurry was then added portionwise to an ice-cold solution of <strong>[67442-07-3]2-chloro-N-methoxy-N-methylacetamide</strong> (28.05g, 203.9 mmol) in NMP (75.7 mL). The resulting mixture was allowed to warm to RT and stirred for 1 day before dilution with EtOAc. The organic layer was washed with NaHCO3 (sat. aq. sol.) and the washings extracted with EtOAc. The organic layers were combined, dried (MgSO4) and evaporated. The residue was purified by column chromatography (silica gel; n-heptane/EtOAc 100/0 to 70/30) to yield 1-1 (13.8 g,49percent).
  • 14
  • [ 635712-99-1 ]
  • [ 2181-42-2 ]
  • 2-(benzyloxy)-5-(oxiran-2-yl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
A solution trimethylsulfonium iodide (495 mg, 2.43 mg) in DMSO (7.5 mL) was added dropwise to a suspension of NaH (prepared from NaH, 101 mg, 2.53 mmol, 60 % in mineral oil by washing with Et20) in THF (7.5 mL) at 0 C. The mixture was stirred at 0 C for 30 min and a solution of <strong>[635712-99-1]6-benzyloxynicotinaldehyde</strong> (450 mg, 2.11 mmol) in THF (3 mL) was added dropwise. The cooling bath was removed and the mixture was stirred at rt for 1 h and poured onto ice. The mixture was extracted with EtOAc and the combined extracts washed with H2O, brine, dried over MgSCU and concentrated to give a quantitative yield of the sub-title compound that was used in the next step without further purification.
  • 15
  • [ 6563-13-9 ]
  • [ 2181-42-2 ]
  • [ 14300-14-2 ]
YieldReaction ConditionsOperation in experiment
92%Chromat. With pyrrolidine; potassium-t-butoxide; In tetrahydrofuran; at 40℃; under 760.051 Torr; for 16h; General procedure: A coupling reaction between <strong>[6563-13-9]6-methoxyquinoline N-oxide</strong> (1a) and trimethylsulfonium iodide (2a) was performed. The results are shown in Table 1.As a result of screening various bases and solvents, the use of KOtBu base in THF promotes the coupling of 1a and 2a to be redox-neutral ( redox-neutral) and the reductive C2-methylated products 3a and 3aa were found to give in good yields (71%).After further optimization, it was found that the use of pyrrolidine as an additional base promotes a high level of yield (91%) and selectivity (15:1 ratio) for the production of 3a (entry 6).From the control entry 9, it was confirmed that the combination of KOtBu and pyrrolidine was essential for the binding of 1a and 2a.In addition, as shown in entry 10, 3a was formed in 95% yield within 3 hours with high chemical selectivity (18: 1).Satisfyingly, this transformation proceeded under mild reaction conditions (40 C.) to afford 3a with a selectivity of 20:1 ratio in 92% yield (entry 11).In addition, as a result of carrying out this reaction on a scale of 1 g, 3a was obtained in 84% yield with almost the same chemical selectivity of 20:1 (entry 12).
  • 16
  • [ 6563-13-9 ]
  • [ 2181-42-2 ]
  • [ 14300-14-2 ]
  • [ 1078-28-0 ]
YieldReaction ConditionsOperation in experiment
With pyrrolidine; potassium-t-butoxide; In tetrahydrofuran; at 80℃; under 760.051 Torr; for 16h; General procedure: A coupling reaction between <strong>[6563-13-9]6-methoxyquinoline N-oxide</strong> (1a) and trimethylsulfonium iodide (2a) was performed. The results are shown in Table 1.As a result of screening various bases and solvents, the use of KOtBu base in THF promotes the coupling of 1a and 2a to be redox-neutral ( redox-neutral) and the reductive C2-methylated products 3a and 3aa were found to give in good yields (71%).After further optimization, it was found that the use of pyrrolidine as an additional base promotes a high level of yield (91%) and selectivity (15:1 ratio) for the production of 3a (entry 6).From the control entry 9, it was confirmed that the combination of KOtBu and pyrrolidine was essential for the binding of 1a and 2a.In addition, as shown in entry 10, 3a was formed in 95% yield within 3 hours with high chemical selectivity (18: 1).Satisfyingly, this transformation proceeded under mild reaction conditions (40 C.) to afford 3a with a selectivity of 20:1 ratio in 92% yield (entry 11).In addition, as a result of carrying out this reaction on a scale of 1 g, 3a was obtained in 84% yield with almost the same chemical selectivity of 20:1 (entry 12).
 

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