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Chemical Structure| 6482-24-2 Chemical Structure| 6482-24-2

Structure of 6482-24-2

Chemical Structure| 6482-24-2

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Product Details of [ 6482-24-2 ]

CAS No. :6482-24-2
Formula : C3H7BrO
M.W : 138.99
SMILES Code : COCCBr
MDL No. :MFCD00000236
InChI Key :YZUPZGFPHUVJKC-UHFFFAOYSA-N
Pubchem ID :80972

Safety of [ 6482-24-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H226-H301-H315-H319-H335
Precautionary Statements:P210-P301+P310+P330-P302+P352-P305+P351+P338
Class:3(6.1)
UN#:1992
Packing Group:

Computational Chemistry of [ 6482-24-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 5
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 25.49
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.88
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

0.84
Log Po/w (WLOGP)?

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

1.03
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.96
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

0.93
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.13

Water Solubility

Log S (ESOL):?

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

-1.1
Solubility 11.1 mg/ml ; 0.0796 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.

-0.62
Solubility 33.6 mg/ml ; 0.242 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

-1.64
Solubility 3.18 mg/ml ; 0.0229 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.

-6.55 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

3.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.86

Application In Synthesis of [ 6482-24-2 ]

* 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 [ 6482-24-2 ]

[ 6482-24-2 ] Synthesis Path-Downstream   1~33

  • 1
  • [ 6086-21-1 ]
  • [ 6482-24-2 ]
  • N-methoxyethyl-N-methyltriazolium bromide [ No CAS ]
  • 2
  • [ 14173-30-9 ]
  • [ 6482-24-2 ]
  • [3-(2-methoxyethoxy)pyridin-2-yl]methanol [ No CAS ]
  • 3
  • [ 6482-24-2 ]
  • [ 189680-06-6 ]
  • 2-bromo-5-(2-methoxy-ethoxy)-benzonitrile [ No CAS ]
  • 4
  • [ 6482-24-2 ]
  • [ 170017-74-0 ]
  • [ 1189556-53-3 ]
YieldReaction ConditionsOperation in experiment
16% With tetra-(n-butyl)ammonium iodide; caesium carbonate; In N,N-dimethyl-formamide; at 65℃; EXAMPLE 6; COMPOUND EXAMPLE 60 Step 1: To the amine 61 (163 mg, 1 equiv.) dissolved in DMF (3 ml) added the cesium carbonate (3 equiv.) and the bromoethyl methyl ether (1.2 equiv.) and heated at 65 C. overnight. If starting material remained, additional bromide and tetra n-butyl ammonium iodide were added and the reaction mixture refluxed (2 days). The mixture was diluted with water, extracted with ethyl acetate, washed with brine (50 mL×3), dried over sodium sulfate, and concentrated in vacuo. The crude product was purified via flash column chromatography (Analogyx, 10-80% ethyl acetate-hexane) to afford the Boc-protected precursor of 62 as a pale yellow oil (30 mg, 16%) with 68% of starting material recovered.
  • 5
  • [ 45865-42-7 ]
  • [ 6482-24-2 ]
  • 5-tert-Butyl-3-(2-methoxyethyl)-4-methyl-1,3-thiazol-2(3H)-ylideneamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% at 85℃; for 24.0h; A mixture of <strong>[45865-42-7]5-tert-butyl-4-methylthiazole-2-ylamine</strong> (1.5 g, 8.8 mmol) and 2-bromoethyl methyl ether (0.91 mL, 9.7 mmol) was warmed to 85 0C and allowed to stir for 24 hours. The crude material was dissolved in ~5 mL of a 1 :1 mixture OfCH2Cl2 and CH3OH and a small amount of silica gel was added. This mixture was concentrated to dryness and the residue was purified via flash column chromatography (SiO2, 9:1 :0.1 CH2Cl2 :CH3OH:NH4OH) to afford the title compound (1.0 g, 4.4 mmol, 50% yield). 1H NMR (300 MHz, CD3OD) delta ppm 1.41 (s, 9 H) 2.38 (s, 3 H) 3.35 (s, 3 H) 3.66 (t, J=4.70 Hz, 2 H) 4.16 (t, J=4.70 Hz, 2 H); MS (DCI/NH3) m/z 229 (M+H)+
at 85℃; for 24.0h; 5-tert-butyl-3-f2-methoxyethvl)-4-methyiotalthiazol:2(3HVimine A mixture of 5-?e/ M}Utyl-4-methylthiazole-2-ylamine (Matrix, 1.5 g, 8.8 mmol) and 2-bromoethyl methyl ether (0.91 mL, 9.7 mmol) was warmed to 85 0C and allowed to stir for 24 hours The mixture was cooled to ambient temperature and material was purified via flash column chromatography (SiO2, 10% methanol in ethyl acetate then 9:1 :0,1 CH2Cl2 : methanol : NH4OH) to afford the title compound. MS (DCI/NH3) m/z 229 (M+H)+.
  • 6
  • [ 6374-91-0 ]
  • [ 6482-24-2 ]
  • 5,7-dibromo-N-(2'-methoxyethyl)isatin [ No CAS ]
  • 7
  • [ 617-05-0 ]
  • [ 6482-24-2 ]
  • [ 196194-41-9 ]
YieldReaction ConditionsOperation in experiment
89% With potassium carbonate; In acetone; The starting material was prepared as follows: A mixture of <strong>[617-05-0]ethyl 4-hydroxy-3-methoxybenzoate</strong> (9.8 g, 50mmol), 2-bromoethyl methyl ether (8.46 ml, 90 mmol) and potassium carbonate (12.42 g, 90 mmol) in acetone (60 ml) was heated at reflux for 30 hours. The mixture was allowed to cool and the solids removed by filtration. The volatiles were removed from the filtrate by evaporation and the residue triturated with hexane to give ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate (11.3 g, 89%) as a white solid. m.p. 57-60 C. 1H NMR Spectrum: (DMSOd6) 1.31(t, 3H); 3.29(s, 3H); 3.32(s, 3H); 3.68(m, 2H); 4.16(m, 2H); 4.28(q, 2H); 7.06(d, 1H); 7.45(d, 1H); 7.56(dd, 1H) MS-FAB: 255 [MH]+
89% With potassium carbonate; In acetone; The starting material was prepared as follows: A mixture of <strong>[617-05-0]ethyl 4-hydroxy-3-methoxybenzoate</strong> (9.8 g, 50 mmol), 2-bromoethyl methyl ether (8.46 ml, 90 mmol) and potassium carbonate (12.42 g, 90 mmol) in acetone (60 ml) was heated at reflux for 30 hours. The mixture was allowed to cool and the solids removed by filtration. The volatiles were removed from the filtrate by evaporation and the residue triturated with hexane to give ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate (11.3 g, 89%) as a white solid. m.p. 57-60 C. 1H NMR Spectrum: (DMSOd6) 1.31(t, 3H); 3.29(s, 3H); 3.32(s, 3H); 3.68(m, 2H); 4.16(m, 2H); 4.28(q, 2H); 7.06(d, 1H); 7.45(d, 1H); 7.56(dd, 1H) MS-FAB: 255 [MH]+
89% With potassium carbonate; In acetone; The starting material was prepared as follows: A mixture of <strong>[617-05-0]ethyl 4-hydroxy-3-methoxybenzoate</strong> (9.8 g, 50 mmol), 2-bromoethyl methyl ether (8.46 ml, 90 mmol) and potassium carbonate (12.42 g, 90 mmol) in acetone (60 ml) was heated at reflux for 30 hours. The mixture was allowed to cool and the solids removed by filtration. The volatiles were removed from the filtrate by evaporation and the residue triturated with hexane to give ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate (1.3 g, 89%) as a white solid. m.p. 57-60 C. 1H NMR Spectrum: (DMSOd6) 1.31(t, 3H); 3.29(s, 3H); 3.32(s, 3H); 3.68(m, 2H); 4.16(m, 2H); 4.28(q, 2H); 7.06(d, 1H); 7.45(d, 1H); 7.56(dd, 1H). MS-FAB: 255 [MH]+
89% With potassium carbonate; In acetone; The starting material was prepared as follows: A mixture of <strong>[617-05-0]ethyl 4-hydroxy-3-methoxybenzoate</strong> (9.8 g, 50 mmol), 2-bromoethyl methyl ether (8.46 ml, 90 mmol) and potassium carbonate (12.42 g, 90 mmol) in acetone (60 ml) was heated at reflux for 30 hours. The mixture was allowed to cool and the solids removed by filtration. The volatiles were removed from the filtrate by evaporation and the residue triturated with hexane to give ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate (11.3 g, 89%) as a white solid. m.p. 57-60 C. 1H NMR Spectrum: (DMSOd6) 1.31(t, 3H); 3.29(s, 3H); 3.32(s, 3H); 3.68(m, 2H); 4.16(m, 2H); 4.28(q, 2H); 7.06(d, 1H); 7.45(d, IH); 7.56(dd, 1H) MS-FAB: 255 [MH]+
89% With potassium carbonate; In acetone; for 30h;Heating / reflux; A mixture of <strong>[617-05-0]ethyl 4-hydroxy-3-methoxybenzoate</strong> (9.8g, 50mmol), 2-bromoethyl methyl ether (8.46ml, 90mmol) and potassium carbonate (12.42g, 90mmol) in acetone (60ml) was heated at reflux for 30 hours. The mixture was allowed to cool and the solids removed by filtration. The volatiles were removed from the filtrate by evaporation and the residue triturated with hexane to give ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate (11.3g, 89%) as a white solid. m.p. 57-60C 1H NMR Spectrum: (DMSOd6) 1.31(t, 3H); 3.29(s, 3H); 3.32(s, 3H); 3.68(m, 2H); 4.16(m, 2H); 4.28(q, 2H); 7.06(d, 1H); 7.45(d, 1H); 7.56(dd, 1H) MS - FAB: 255 [MH]+

  • 8
  • [ 617-05-0 ]
  • [ 6482-24-2 ]
  • [ 196194-41-9 ]
  • [ 97966-31-9 ]
YieldReaction ConditionsOperation in experiment
PREPARATION 134(1) Ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate (5.69 g) was obtained as colorless powders from <strong>[617-05-0]ethyl 4-hydroxy-3-methoxybenzoate</strong> (5.00 g) and 2-methoxyethyl bromide (3.59 mL) in a manner similar to Preparation 131(2). NMR (CDCl3, delta): 1.39 (3H, t, J=7 Hz), 3.46 (3H, s), 3.81 (2H, t, J=4 Hz), 3.91 (3H, s), 4.23 (2H, t, J=4 Hz), 4.35 (2H, q, J=7 Hz), 6.91 (1H, d, J=8 Hz), 7.55 (1H, d, J=4 Hz), 7.65 (1H, dd, J=4, 8 Hz).
  • 9
  • [ 52427-05-1 ]
  • [ 6482-24-2 ]
  • [ 1041853-13-7 ]
YieldReaction ConditionsOperation in experiment
98% With caesium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 30℃; for 2h;Inert atmosphere; In a 25 m round-bottomed fiask, <strong>[52427-05-1]2-bromo-5-nitrophenol</strong> (600 mg, 2.75 mmol, Eq: 1.00), cesium carbonate (1.35 g, 4.13 mmol, Eq: 1.5) and potassium iodide (9 1.4 mg, 550 imol, Eq:0.2) were combined with dimethylformamide (10 ml) and under argon 1 -bromo-2- methoxyethane (574 mg, 388 jil, 4.13 mmol, Eq: 1.5) was added. The reaction mixture was stirred at 30 °C for 2 hours. The reaction mixture was concentrated in yacuo and water was added (40 ml). The reaction mixture was extracted with ethyl acetate (3 x 30 ml). The organie phase was dried oyer magnesium sulfate and concentrated in yacuo to yield 1-bromo-2-(2- methoxyethoxy)-4-nitrobenzene (?748 mg. 98percent) as a brown solid. 1H-NMR (ppm. 300 MHz. CDC13): 7.76-7.77 (m, 1H), 7.72-7.73 (m, 2 H), 4.29 (t, 2 H), 3.85 (t, 2 H), 3.49 (s, 3 H).
91% potassium iodide; In N,N-dimethyl-formamide; at 70℃; for 4h; Method 10 l-Bromo-2-(2-methoxyethoxy)-4-nitrobenzene. To a solution of <strong>[52427-05-1]2-bromo-5-nitrophenol</strong> (7.24 g, 33.2 mmol) (Method 9) in anhydrous DMF was added 2-methoxy-l-bromoethane (6.92 g, 49.8 mmol) and a catalytic amount of potassium iodide (~ 100 mg). The reaction was heated at 70 0C for 4 h before being allowed to cool to rt. The reaction was then poured into a separatory funnel and partitioned between EtOAc (~ 250 mL) and water (~ 250 mL). The organic phase was dried over Na2SO4 and cone in vacuo giving the crude title compound which was taken up in a minimum volume of warm EtOAc. The resulting solution was cooled in an ice bath and hexanes were slowly added to induce crystallization. The resulting precipitate was isolated via vacuum filtration through a fritted funnel and air dried to give pure title compound (8.3 g, 91percent). 1H NMR: (300 MHz) 7.87-7.92 (m, 2 H), 7.76 (dd, 1 H), 4.35 (t, 2 H), 3.73 (t, 2 H), 3.35 (s, 3 H).
91% potassium iodide; In N,N-dimethyl-formamide; at 70℃; for 4h; To a solution of <strong>[52427-05-1]2-bromo-5-nitrophenol</strong> (7.24 g, 33.2 mmol) (Method 9) in anhydrous DMF was added 2-methoxy-l-bromoethane (6.92 g, 49.8 mmol) and a catalytic amount of potassium iodide (~ 100 mg). The reaction was heated at 70 0C for 4 h before being allowed to cool to rt. The reaction was then poured into a separatory funnel and partitioned between EtOAc (~ 250 mL) and water (~ 250 mL). The organic phase was dried over Na2SO4 and cone in vacuo giving the crude title compound which was taken up in a minimum volume of warm EtOAc. The resulting solution was cooled in an ice bath and hexanes were slowly added to induce crystallization. The resulting precipitate was isolated via vacuum filtration through a fritted funnel and air dried to give pure title compound (8.3 g, 91percent). 1H NMR: (300 MHz) 7.87-7.92 (m, 2 H), 7.76 (dd, 1 H), 4.35 (t, 2 H), 3.73 (t, 2 H), 3.35 (s, 3 H)
  • 10
  • [ 5470-65-5 ]
  • [ 6482-24-2 ]
  • [ 1088145-50-9 ]
  • 11
  • [ 936247-35-7 ]
  • [ 6482-24-2 ]
  • [ 1144110-06-4 ]
YieldReaction ConditionsOperation in experiment
60% 5-Chloro-2-nitro-pyridine-3-ol (1.15 mmol) is dissolved in DMF (2 ml) and NaH (1.4 eq., 60% suspension in liquid paraffin) is added and the suspension is stirred 45 min at room temperature. 1-Bromo-2-methoxy- ethane (1 eq.) is added and the reaction suspension is heated to 100 0C for 24 hours. The reaction solution is pored into water and extracted with dichloromethane. The combined organic layers are washed with brine, <n="62"/>dried over MgSO4 and the solvent is removed in vacuo. 5-Chloro-3-(2- methoxy-ethoxy)-2-nitro-pyridine is obtained after column chromatography as beige solid in a yield of 60 %; mp. 71.5-72.5; HPLC (method C): 1.63 min; LC-MS (method A): 1.36 min, 232.95 (M+H+).
  • 12
  • [ 6482-24-2 ]
  • [ 52867-42-2 ]
  • [ 1005788-32-8 ]
YieldReaction ConditionsOperation in experiment
94% With potassium carbonate; In N,N-dimethyl-formamide; Reference Example 61 Production of methyl 3-(2-methoxyethoxy)-1-methyl-1H-pyrazole-5-carboxylate Using <strong>[52867-42-2]methyl 3-hydroxy-1-methyl-1H-pyrazole-5-carboxylate</strong> (2.34 g, 15.0 mmol), 1-bromo-2-methoxyethane (3.13 g, 22.5 mmol), potassium carbonate (4.15 g, 30.0 mmol) and N,N-dimethylformamide (15 mL), and in the same manner as in Reference Example 57, the title compound (3.03 g, yield 94%) was obtained. 1H-NMR (DMSO-d6, 300 MHz) delta 3.28 (3H, s), 3.57-3.64 (2H, m), 3.81 (3H, s), 3.93 (3H, s), 4.14-4.20 (2H, m), 6.28 (1H, s).
  • 13
  • [ 52351-75-4 ]
  • [ 6482-24-2 ]
  • [ 1103774-16-8 ]
  • 14
  • [ 269410-08-4 ]
  • [ 6482-24-2 ]
  • [ 847818-71-7 ]
YieldReaction ConditionsOperation in experiment
90% With potassium carbonate; In N,N-dimethyl-formamide; at 160℃; for 2h;Microwave irradiation; A mixture of 4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1H-pyrazole (1.94 g, 10 mmol), 2-bromoethyl methyl ether (1.68 g, 12 mmol) and K2C03 (2.76 g, 20 mmol) in DMF (16 mL) was stirred at 160 °C for 2 h in the microwave. The reaction mixture was concentrated and purified by silica gel chromatography (30percent EA:PE) to give 2.2 g (90percent) of the title compound as yellow oil. ?H NMR (400 MHz, CDC13): oe 1.32 (12H, s), 3.32 (3H, s), 3.75 (2H, t, J= 5.2 Hz), 4.30 (2H, t, J= 5.2 Hz), 7.77 (1H, s), 7.79 (1H, s). [M+H] Calc?d for C,2H2,BN203, 253; Found, 253.
68% With caesium carbonate; In N,N-dimethyl-formamide; at 150℃; for 0.5h;Microwave irradiation; Example A68Preparation of intermediate 68: l-(2-Methoxy-ethyl)-4-(4,4,5,5-tetramethyl- [l,3,21dioxaborolan-2-yl)-7H-pyrazoleA mixture of 4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-7H-pyrazole (1 g, 5.15 mmol), 2-bromoethyl methyl ether (0.63 ml, 6.7 mmol) and cesium carbonate (2.52 g, 7.73 mmol) in N,N-dimethylformamide (7 ml) was stirred at 150 °C for 30 min. under microwave irradiation. The mixture was partitioned between water and diethyl ether. The organic layer was separated, dried (Na2S04), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; ethyl acetate in heptane 30/70). The desired fractions were collected and concentrated in vacuo to yield intermediate 68 (0.88 g, 68percent) as a pale yellow oil.
68% With caesium carbonate; In N,N-dimethyl-formamide; at 150℃; for 0.5h;microwave irradiation; Example A68Preparation of intermediate 68: 1-(2-Methoxy-ethyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazoleA mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (1 g, 5.15 mmol), 2-bromoethyl methyl ether (0.63 ml, 6.7 mmol) and cesium carbonate (2.52 g, 7.73 mmol) in N,N-dimethylformamide (7 ml) was stirred at 150° C. for 30 min. under microwave irradiation.The mixture was partitioned between water and diethyl ether.The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo.The crude product was purified by flash column chromatography (silica; ethyl acetate in heptane 30/70).The desired fractions were collected and concentrated in vacuo to yield intermediate 68 (0.88 g, 68percent) as a pale yellow oil.
57% With caesium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; 2-Bromoethyl methyl ether (0.93 g, 6.70 mmol, 0.64 mL) was added to a mixture of 4-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (1 .00 g, 5.15 mmol) and caesium carbonate (3.49 mg, 10.72 mmol) in dry N,N-dimethylformamide (20 mL) at 0°O. After stirring for 30 mm the ice-water bath was removed. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (150 mL) and washed with brine(3x100 mL). The organic layer was dried with sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (Method L7; 12 g; heptane, 10percent-30percent ethyl acetate) afforded 0.74 g (2.92 mmol; 57percent of theory) of the title compound.GO-MS (Method L9): R1 = 4.21 mm; m/z = 251 MH NMR (300 MHz, Ohloroform-d, Method M2) 6 7.79 (s, 1 H), 7.76 (s, 1 H), 4.29 (t, J = 5.3 Hz,2H), 3.75 (t, J = 5.3 Hz, 2H), 3.32 (s, 3H), 1.31 (s, 12H).
56% General procedure: Preparation 122: 1 -(2-Methoxyethyl)-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H- Method H NaH (60percent, 83 mg) was added to a solution of 4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-1 - -pyrazole (204 mg, 1 .05 mmol) in DMF (4 mL). After stirring for 15 minutes, 1 -bromo-2-methoxyethane (175 mg, 1 .26 mmol) in DMF (1 mL) was added. The resulting solution was stirred at 80°C under microwave irradiation for 60 minutes. The reaction mixture was diluted with brine and extracted with EtOAc. The combined organic layers were washed with water, dried with Na2S04j and concentrated in vacuo to afford the title compound as a yellow oil that was used directly in the next step (148 mg, 56percent). 1 H NMR (500 MHz, CDCI3): delta 7.80 (d, J = 0.7 Hz, 1 H), 7.77 (d, J = 0.7 Hz, 1 H), 4.31 (t, = 5.3 Hz, 2H), 3.76 (t, J = 5.3 Hz, 2H), 3.33 (s, 3H), 1.32 (s, 12H). LCMS (ESI) Rt = 2.17 minutes MS m/z 253 [M+H]+
26% To a solution of 4-(tetramethyl-1 ,3, 2-dioxaborolan-2-yl)-1H-pyrazole (1 .00 g, 5.1 mmol) in DMF (5 mL) was added sodium hydride (245 mg of a 60percent dispersion in mineral oil, 6.1 mmol) at room temperature. The mixture was then stirred at room temperature for 60 minutes. The mixture was cooled to 0 ° C and 2-bromoethyl methyl ether (0.72 mL, 7.7 mmol) was added drop wise via syringe. After complete addition, the mixture was allowed to warm to room temperature and stirred for an hour prior to addition of ethyl acetate (70 mL) and water (30 mL). The organic layer was separated, washed with water (2 x 30 mL) and brine (30 mL), dried (Na2S04), filtered and concentrated at reduced pressure. The residue was purified by Biotage Isolera? chromatography [Biotage SNAP Cartridge KP-Sil 50 g; using a gradient of eluents, 0-50percent EtOAc in heptane] to give the title compound (333 mg, 26percent yield) as a colourless oil. 1H NMR (250 MHz, DMSO-d6) delta [ppm] 7.88 (s, 1 H), 7.57 (s, 1 H), 4.32 - 4.20 (m, 2H), 3.73 - 3.60 (m, 2H), 3.21 (s, 3H), 1 .25 (s, 12H). LCMS (Analytical Method A): Rt = 1 .01 mins, MS (ESIPos): m/z = 253 (M+H)\
20% With potassium hydroxide; In ethanol; at 50℃; for 76h; Intermediate 1171 -[2-(Methyloxy)ethyl]-4-(4,4,5,5-tetrameth l-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazolA solution of 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (10 g, 51 .5 mmol) in ethanol (50 mL) was treated with KOH (3.47 g, 61 .8 mmol) and 1 -bromo-2- (methyloxy)ethane (5.81 mL, 61.8 mmol) at room temperature and the resulting mixture was stirred at 50°C under nitrogen for 16 h then cooled to room temeprature. 1 -Bromo-2- (methyloxy)ethane (2 ml_, 21 .3 mmol) was added and the resulting mixture was stirred at 50°C for 60 h then cooled to room temperature. The mixture was filtered through celite and the insoluble were washed with ethanol. The combined filtrate and washings were concentrated in vacuo. Purification of the residue on SP4 using a 100 G silica cartridge (gradient: 0 to 100percent AcOEt in Hexanes) gave 1 -[2-(methyloxy)ethyl]-4-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 /-/-pyrazole (2.72 g, 10.25 mmol, 20percent) as a yellow oil. LCMS (method G): Retention time 0.87 min, [M+H]+ = 252.9
20% With potassium hydroxide; In ethanol; at 50℃; for 66h;Inert atmosphere; A solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (10 g, 51.5 mmol) in ethanol (50 mL) was treated with KOH (3.47 g, 61.8 mmol) and 1-bromo-2-(methyloxy)ethane (5.81 mL, 61.8 mmol) at room temperature and the resulting mixture was stirred at 50° C. under nitrogen for 16 h then cooled to room temperature. 1-Bromo-2-(methyloxy)ethane (2 mL, 21.3 mmol) was added and the resulting mixture was stirred at 50° C. for 60 h then cooled to room temperature. The mixture was filtered through celite and the insoluble were washed with ethanol. The combined filtrate and washings were concentrated in vacuo. Purification of the residue on SP4 using a 100 G silica cartridge (gradient: 0 to 100percent AcOEt in Hexanes) gave 1-[2-(methyloxy)ethyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.72 g, 10.25 mmol, 20percent) as a yellow oil. LCMS (method G): Retention time 0.87 min, [M+H]+=252.9
With caesium carbonate; In N,N-dimethyl-formamide; at 90℃; for 2h;microwave irradiation; A solution of 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.8 g, 4.1 mmol), cesium carbonate (2.0 g, 6.2 mmol), and l-bromo-2-methoxyethane (0.41 rnL, 4.3 mmol) in DMF (14 rnL) was heated in a microwave at 900C for 1 hr. After the initial heating, additional l-bromo-2-methoxyethane (0.41 rnL) was added to the reaction. Heating was repeated for an additional 1 hr. The crude reaction mixtures were then diluted with water (250 mL) and extracted with ethyl acetate (3 x 50 mL). Product was purified by silica gel column using DCM/EtOAc/MeOH (8/1.5/0.5) as eluent to give l-(2-methoxyethyl)-4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (1.2 g) as a light yellow oil. ESI- MS :m/z 253.2 (M+H)+.
With caesium carbonate; In acetonitrile; at 90℃; Step I : l-(2-methoxyethyl)-4-(4, 4, 5, 5-tetramethyl-L 3, 2-dioxaborolan-2-yl)-W-pyrazoIe; A mixture of [A] 4-(4,4,5s5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l H-pyrazole ( 100 mg, 0.5 mmol), 2-bromoethyl methyl ether (58 uL, 0.62 mmol, Aldrich, Cat. No. 238155), and cesium carbonate (500.0 mg, 1.5 mmol) in acetonitrile (1 mL) was stirred at 90 0C overnight. After cooling it was quenched with water, extracted with ethyl acetate. The extract was washed with water twice, brine once; dried over Na2SO4. After filtration the filtrate was concentrated to yield 90 mg of the product. LCMS (M+H)+: m/z = 253.1
With sodium hydride; In tetrahydrofuran; mineral oil; for 24h;Reflux; ntermediate 1 1 1 -(2-methoxyethyl)-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole[094] A mixture of 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (200 mg, 1 .03 mmol),1 -bromo-2-methoxyethane (280 mg, 2.01 mmol), and NaH (200 mg, 4 mmol) in THF (15 mL) was stirred at reflux for 24 hours, cooled to the ambient temperature, and concentrated in vacuo. The residue was treated with HCI(aq) and extracted with EtOAc. The insoluble solid was removed by filtration, and the organic solution was concentrated to give the title compound. MS (m/z): 253 (M.bul.H)+.
25.4 g With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; 4-(4,4,5,5-Tetramethyl-[1 ,3,2]clioxaborolan-2-yl)-1 H-pyrazole (19.4 g, 0.10 mol), 1- bromo-2-methoxy-ethane (14.18 ml, 0.15 mol), and caesium carbonate (32.58 g, 0.1 mol) are dissolved in DMF (200 ml). The suspension is stirred for 16 h at 80°C, filtered and the solvent is removed in vacuum. The residue is treated with tert-butyl methyl ether (200 ml), filtered over Celite and then the solvent is removed in vacuum; yield: 25.4 g 1-(2-methoxy-ethyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxa- borolan-2-yl)-1H-pyrazole; HPLC/MS: 1.82 min, [M+H] = 253.
With sodium hydride; In tetrahydrofuran; for 24h;Reflux; A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (200 mg, 1.03 mmol), 1-bromo-2-methoxyethane (280 mg, 2.01 mmol), and NaH (200 mg, 4 mmol) in THF (15 mL) was stirred at reflux for 24 hours, cooled to the ambient temperature, and concentrated in vacuo. The residue was treated with HCl(aq) and extracted with EtOAc. The insoluble solid was removed by filtration, and the organic solution was concentrated to give the title compound. MS (m/z): 253 (M+H)+.
1.31 g With caesium carbonate; In acetonitrile; at 50℃;Inert atmosphere; 1H-pyrazole-4-boronic acid pinacol ester (1.0 g, 5.155 mmol),2-Bromoethyl methyl ether (0.788 g, 5.669 mmol)And cesium carbonate (5.04 g, 15.469 mmol) were dissolved in acetonitrile (20 mL),The mixture was stirred under nitrogen at 50 ° C overnight,filter,Concentrate to dryness to give 1- (2-methoxyethyl) -1H-pyrazole-4-boronic acid pinacol ester (1.310 g).

  • 15
  • [ 145576-28-9 ]
  • [ 6482-24-2 ]
  • [ 1292279-24-3 ]
YieldReaction ConditionsOperation in experiment
74% Example 223(5a,8a)-2-(4-Cyclopropyl-phenyl)-8-hydroxy-8-methoxymethyl-2-aza-spiro[4.5]decan-l- oneStep 1: l-(2-Methoxy-ethyl)-4-methylene-cyclohexanecarboxylic acid ethyl ester A solution of 5 g (30 mmol) 4-methylene-cyclohexanecarboxylic acid ethyl ester (commercially available) in 19 mL THF was added to 59 mmol LDA in 75 mL THF at - 5 C and stirred for 3 h. 8.2 g (59 mmol) 2-bromoethyl methyl ether in 10 mL THF was added and the mixture was allowed to stir to room temperature and stirred additionally over night. Water and 2M Na2C03 aq. was added and the mixture was evaporated to dryness. The residue was taken up in ethyl acetate washed with water and brine, dried with MgS04, filtered and evaporated. The residue was purified by flash columnchromatography over silica eluting with a gradient formed from hexane and ethyl acetate to yield after evaporation of the product containing fractions 4.98 g (74 %) of the title compound as yellow liquid.
74% Step 1: 1-(2-Methoxy-ethyl)-4-methylene-cyclohexanecarboxylic acid ethyl ester A solution of 5 g (30 mmol) 4-methylene-cyclohexanecarboxylic acid ethyl ester (commercially available) in 19 mL THF was added to 59 mmol LDA in 75 mL THF at -5 C. and stirred for 3 h. 8.2 g (59 mmol) 2-bromoethyl methyl ether in 10 mL THF was added and the mixture was allowed to stir to room temperature and stirred additionally over night. Water and 2M Na2CO3 aq. was added and the mixture was evaporated to dryness. The residue was taken up in ethyl acetate washed with water and brine, dried with MgSO4, filtered and evaporated. The residue was purified by flash column chromatography over silica eluting with a gradient formed from hexane and ethyl acetate to yield after evaporation of the product containing fractions 4.98 g (74%) of the title compound as yellow liquid.
  • 16
  • [ 1196473-37-6 ]
  • [ 6482-24-2 ]
  • [ 1268390-33-5 ]
  • 17
  • [ 128562-95-8 ]
  • [ 6482-24-2 ]
  • [ 1313043-30-9 ]
YieldReaction ConditionsOperation in experiment
72% A. 1 -(2-Methoxy-ethyl)-4-trifluoromethyl-1 H-indole A mixture of 4-trifluoromethyl-1 H-indole (105 mg, 0.57 mmol), powder KOH (159 mg, 2.83 mmol) in DMSO (6 mL) is stirred at r.t. for 5 min. 2-Methoxyethyl bromide (80 muIota_, 0.85 mmol) is added. After the reaction mixture is stirred at r.t. overnight, it is partitioned between H2O and Et2O. The two layers are separated, and the aqueous layer is extracted with Et2O (3x). The combined organic extracts are washed with H2O and brine, dried over MgSO , filtered, and concentrated in vacuo. The crude material is purified on silica gel with heptane/EtOAc (100/0 to 70/30) as eluent to yield the product (100 mg, 72%) as a clear colorless liquid.1 H NMR (300 MHz, CDCI3) delta 7.53 (d, J = 8.2 Hz, 1 H), 7.40 (d, J = 7.3 Hz, 1 H), 7.35- 7.20 (m, 2H), 6.69 (s, 1 H), 4.32 (t, J = 5.4 Hz, 2H), 3.71 (t, J = 5.4 Hz, 2H), 3.31 (s, 3H);19F NMR (300 MHz, CDCI3) delta -60.99 (s, 3F);LC Rt: 3.21 min; MS 244 (M+H, 100%).
  • 18
  • [ 6482-24-2 ]
  • [ 17288-32-3 ]
  • [ 1313266-73-7 ]
YieldReaction ConditionsOperation in experiment
71% To a solution of lH-pyrrolo[3,2-b]pyridine-2-carboxylic acid ethyl ester (1.34 g, 7.04 mmol) [prepared according to the procedure by Lachance, N. et al. Synthesis 2005, 15, 2571 -2577] in N,N- dimethylacetamide at rt is added sodium hydride (210 mg, 8.31 mmol). The resulting mixture is stirred for 30 minutes at rt. 2-Bromoethylmethyl ether (1.4 mL, 14.15 mmol) is added and the resulting mixture is stirred at rt overnight. The mixture is diluted with water and EtOAc. The organic is separated and the aqueous phase is extracted with EtOAc. The organic phase is washed with brine then separated and dried (MgSO/t). The organic phase is concentrated in vacuo and the crude residue is flash chromatographed over Si02 (eluted with heptane:EtOAc = 85: 15) to afford 1.24 g (71percent) of the title compound as a yellow oil. lH NMR (CDC13, 300 MHz) delta 8.56 (m, 1H), 7.82 (d, 1H), 7.46 (s, 1H), 7.24-7.20 (m, 1H), 4.73 (m, 2H), 4.40 (m, 2H), 3.73 (m, 2H), 3.24 (m, 3H), 1.43 (m, 3H). LCMS m/z 249 (M+H).
  • 19
  • [ 7768-28-7 ]
  • [ 6482-24-2 ]
  • [ 1380495-39-5 ]
  • 20
  • [ 109431-87-0 ]
  • [ 6482-24-2 ]
  • [ 1212413-55-2 ]
YieldReaction ConditionsOperation in experiment
51% To a stirred solution of NaH (3.8 g, 95 mmol, 60% in mineral oil w/w) in THF (20 ml) under N2atmosphere at 0 C, was added tert-butyl (R)-3-hydroxypyrrolidine-l- carboxylate (step 1, 4.5 g, 24 mmol) in THF (40 ml). After 30 minutes l-bromo-2- methoxyethane (3.4 ml, 36 mmol) was added, the reaction mixture was slowly allowed to attain to room temperature and stirred for overnight. After completion of the reaction (monitored by TLC), the reaction mixture was quenched by addition of saturated NH4C1 solution at 0 C. The solution was extracted with EtOAc (2x100 mL), the combined organic phases were washed with brine, dried over Na2S04and concentrated under reduced pressure to give the crude product. Purification by flash chromatography with EtOAc-hexane (2: 8) as an eluent to afford the desired product (3.0 g, yield: 51%) as an oil. 1H MR (300 MHz, CDC13): δ 4.10-4.05 (m, 1H), 3.60-3.52 (m, 4H), 3.45-3.36 (m, 4H), 3.38 (s, 3H), 2.02-1.93 (m, 2H), 1.45 (s, 9H).
  • 21
  • [ 6482-24-2 ]
  • [ 4983-28-2 ]
  • [ 61533-68-4 ]
YieldReaction ConditionsOperation in experiment
85% With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 16h;Inert atmosphere; j0399j 2-Chloropyrimidin-5-ol (200 mg, 1.53 mmol), 1-bromo-2-methoxyethane (0.158 mL, 1.69 mmol) and potassium carbonate (423.5 mg 3.06 mmol) were suspended in anhydrous NN-dimethylformamicle (5 mL) and heated 10 50 °C in a nitrogen almosphere for 16 hours. The solvents were removed in vacuo and the residue was partitioned between ethyl acetate (50 mL) and water (30 mL), the aqueous was extracted with ethyl acetate (2 x 30 niL) and the conbilled organics washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give the title compound 244 mg (yield 85percent) as off-white translucent crystals. &i NMR (500 MHz, DMSO) 8.55 (s, 2F1), 4.37 ?4.21 (m, 2H), 3.78 ? 3.59 (m, 2H), 3.30 (s, 3H). Tr(METCRI278) = 1.36 mill, (Est) (M+Na)t 189.
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 26h; To a stirred solution of 2-chloropyrimidm-5-ol (Intermediate No.86 Step 2, 17.5 g, 134 mmol) in DMF (90 mL was added 2-bromoethyl methyl ether (17.6 mL, 1-87 mmol) followed by K2C03 (24.0 g, 174 mmol). The. resulting suspension was heated at 60 °C for 18 hr. In order to drive the reaction to completion, additional 2-bromoethyl methyl ether (16.0 mL, 170 mmol) and K2C03 (18.5 g, 134 mmol) were added, and- the heating was continued for approximately 8 hr. The reaction mixture was cooled and partitioned between 10percent aqueous sodium chloride (250 mL) and EtOAc (500 mL). The layers were separated and the organic layer was washed with 10percent aqueous sodium chloride (250 mL). The first aqueous layer was extracted with EtOAc (250 mL). The second aqueous layer was salted with solid NaCl, and extracted with EtOAc (250-mL). The combined organic layers were driecLover Na2S04, filtered, andconcentrated to a crude oil that was taken up into a minimal amount of DCM and purified by silica gel chromatography to afford 2-chIoro-5-(2-methoxyethoxy)pyrimidine as a white solid. LRMS (ESI) calc'd for C7H10C1N2O2 [M+Hf: 189. ; found 189.
  • 22
  • [ 17288-53-8 ]
  • [ 6482-24-2 ]
  • [ 1443411-49-1 ]
  • 23
  • [ 26215-14-5 ]
  • [ 6482-24-2 ]
  • 7-amino-4-(2-methoxyethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% With potassium carbonate; In N,N-dimethyl-formamide; for 24h; 2-Bromoethyl methyl ether (1.20 mmol, 0.11 mL) was added to a suspension of 7-amino-2H-benzo [b] [l,4]oxazin- 3(4H)-one (1.00 mmol, 0.16 g) and potassium carbonate (2.00 mmol, 0.28 g) in DMF (5 mL) and the mixture was stirred for 24 hours. Water was added and the mixture was extracted with ethyl acetate. The combined organic extracts were dried (MgS04) and concentrated under reduced pressure. The residue was purified by column (0703) chromatography (silica gel, gradient of 0-5% methanol in dichloromethane) to give the title compound as a yellow solid (0.05 g, 22%) .
  • 24
  • [ 6482-24-2 ]
  • [ 131818-17-2 ]
  • tert-butyl (4-bromophenyl)(2-methoxyethyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
96.1% A mixture of sodium hydride (60, 160 mg, 4.00 mmol) and tert-butyl (4-bromophenyl) carbamate (598 mg, 2.20 mmol) in DMF (20 mL) was stirred at 0 under N2for 0.5 h. To the mixture was added 1-bromo-2-methoxyethane (400 mg, 2.88 mmol) . The resulting mixture was warmed to 80 and stirred for 3 h. The reaction mixture was cooled to rt and quenched with saturated aqueous NaCl (50 mL) . The resulting mixture was extracted with EtOAc (50 mL × 3) . The combined organic layers were concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE/EtOAc (v/v) 15/1 to give a light yellow solid product (696 mg, 96.1) .[0938]MS (ESI, pos. ion) m/z: 230.2 [M-99]+
  • 25
  • [ 610-37-7 ]
  • [ 6482-24-2 ]
  • 2-methoxyethyl 5-(2-methoxyethoxy)-2-nitrobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; To a solution of <strong>[610-37-7]5-hydroxy-2-nitrobenzoic acid</strong> (915 mg, 5.00 mmol) in DMF (5.6 mL) was added K2C03 (1.38 g, 10.00 mmol), and 2-bromomethyl methyl ether (2.08 g, 15 mmol, 1.41 mL). The reaction mixture was heated at 80 C overnight. Tic showed all of the starting benzoic acid was consumed and one new spot formed. No ion for the product was seen in the MS but there was one peak in the LC. The mixture was cooled to rt and poured into water. The aqueous mixture was extracted with EtOAc twice and the combined organic layers were washed with saturated NaCl, decanted from the drying agent, and concentrated in vacuo to give 1.45 g, 97%, of a yellow oil. The material is used as is in the next step.
34.3% With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; A mixture of <strong>[610-37-7]5-hydroxy-2-nitrobenzoic acid</strong> (500 mg, 2.73 mmol), potassium carbonate (1.51 g, 11 mmol), and 2-methoxyethyl bromide (1.5 mL, 15.96 mmol) in DMF (20 mL) was stirred at 100 C overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with water and brine. After dried by sodium sulfate and concentration, the residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate=1:1) to giveIas a yellow oil (280mg, 34.3%).1H NMR (300 MHz, CDCl3)delta8.04 (d,J= 8.9 Hz, 1H), 7.14-7.01 (m, 2H), 4.57-4.36 (m, 2H), 4.25-4.04 (m, 2H), 3.84-3.73 (m, 2H), 3.73-3.62 (m, 2H), 3.44 (s, 3H), 3.39 (s, 3H).
  • 26
  • [ 78430-91-8 ]
  • [ 6482-24-2 ]
  • 1-(4-ethenylbenzyl)-3-(2-methoxyethyl)-1H-imidazol-3-ium bromide [ No CAS ]
  • 27
  • [ 93247-78-0 ]
  • [ 6482-24-2 ]
  • methyl 1-(2-methoxyethyl)-1H-indole-7-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
A solution of <strong>[93247-78-0]methyl 1H-indole-7-carboxylate</strong> (1 g, 5.71 mmol) in DMF (30 mL) was added NaH (274 mg, 6.86 mmol) at 0C. After stirring for 45 minutes, 1-bromo-2-methoxyethane (946 mg, 6.86 mmol) was added and stirred for 16 hours at a it was quenched with water, extracted with EA (x3), washed with brine (x2). The organic layer was dried, and concentrated to give the cmde methyl 1-(2-methoxyethyl)-1H-indole-7-carboxylate as a yellow oil (680 mg, 5 1%). ESI MS m/z = 233.9 [M+Hf
A solution of <strong>[93247-78-0]methyl 1H-indole-7-carboxylate</strong> (1 g, 5.71 mmol) in DMF (30 mL) was added NaH (274 mg, 6.86 mmol) at 0°C. After stirring for 45 minutes, 1-bromo-2-methoxyethane (946 mg, 6.86 mmol) was added and stirred for 16 hours at rt. It was quenched with water, extracted with EA (x3), washed with brine (x2). The organic layer was dried, and concentrated to give the crude methyl 1-(2-methoxyethyl)-1H-indole-7-carboxylate as a yellow oil (680 mg, 51percent). ESI MS m/z = 233.9 [M+H]+.
  • 28
  • [ 6482-24-2 ]
  • [ 31785-05-4 ]
  • ethyl 5-((2-methoxyethyl)amino)-2-methylthiazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; for 7h; A solution of <strong>[31785-05-4]ethyl 5-amino-2-methylthiazole-4-carboxylate</strong> (1.7 g, 9.0 mmol), 1-bromo-2- methoxyethane (1.2 g, 9.0 mmol) and C52CO3 (4.4 g, 13.5 mmol) in DMF (10 mL) was heatedto 50 C for 7 hours and then cooled to r.t. The crude product was purified by reverse phaseC18 column chromatography (MeCN/H20) to give ethyl 5-((2-methoxyethyl)amino)-2-methylthiazole-4-carboxylate as an orange oil (850 mg, 3.48 mmol, 39%). ESI-MS m/z: 245.2[M+Hj .
39% With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; for 7h; A solution of <strong>[31785-05-4]ethyl 5-amino-2-methylthiazole-4-carboxylate</strong> (1.7 g, 9.0 mmol), 1-bromo-2- methoxyethane (1.2 g, 9.0 mmol) and Cs2CO3 (4.4 g, 13.5 mmol) in DMF (10 mL) was heated to 50C for 7 hours and then cooled to r.t. The crude product was purified by reverse phase C18 column chromatography (MeCN/H2O) to give ethyl 5-((2-methoxyethyl)amino)-2- methylthiazole-4-carboxylate as an orange oil (850 mg, 3.48 mmol, 39%). ESI-MS m/z: 245.2 [M+H]+.
  • 29
  • [ 34334-96-8 ]
  • [ 6482-24-2 ]
  • 1-(2-methoxyethyl)-5-methyl-3-nitro-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With potassium carbonate; In acetonitrile; at 75℃; for 3h; Add acetonitrile (35 mE) to a mixture of 5-methyi-3-nitro-1H-pyrazoie (095 g,7.1 minol), potassium carbonate (2.0 g, 2.0 eq), and I-brorno-2-methoxyethane (2.0 rnL,3.0 eq). Stir at 75 C for three hours. Cool to rt. Add diethyl ether (-35 mL) and filter. Rinse the solids with EtOAc (2 x 25 rnL). Concentrate the filtrate in vacuo to provide aresidue. Subject the residue to normal phase chromatography, eluting with a 0-100%EtOAc in hexanes gradient, to give the title compound as a yellow oil (1.1 g, 64%). MS(ES) m/z = 186 (M-i-H).
  • 30
  • [ 35344-95-7 ]
  • [ 6482-24-2 ]
  • [ 304693-70-7 ]
YieldReaction ConditionsOperation in experiment
65% With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; To a solution of lH-pyrazole-4-carbaldehyde (500 mg, 5.20 mmol) in DMF (20 mL) was added l-bromo-2-methoxyethane (713 mg, 5.2 mmol) and CS2CO3 (3.40 g, 10.4 mmol). After stirring at 60 °C overnight, water (20 mL) was added to the mixture and the mixture was extracted with EtOAc (50 ml x 3). The organic phase was washed with brine, dried over Na2S04 and concentrated to yield intermediate 50 (520 mg, 65percent> yield).
55% With caesium carbonate; In acetonitrile; for 2h;Reflux; 1H-pyrazole-4-carbaldehyde (0.5 g; 5.2 mmol) and cesium carbonate (3.39 g; 10.4mmol) were diluted in ACN (10 mL). Then, 2-bromoethyl methyl ether (0.636 mL; 6.77 mmol) was added and the reaction mixture was refluxed for 2 hours. The reaction mixture was partitionned between a saturated solution of NaHCO3 and EtOAc. The organic layer was separated, dried over MgSO4, filtered and concentrated.The residue was purified by silica gel chromatography (irregular Si02, 120 g, DCM/MeOH: 100/0 to 95/5). The fractions containing the product were mixed andconcentrated to afford 439 mg (55percent) of intermediate 35.
  • 31
  • [ 61367-62-2 ]
  • [ 6482-24-2 ]
  • 2-bromo-1,3-dimethoxy-5-((2-methoxyethoxy)methyl)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% To a round bottom flask was added <strong>[61367-62-2](4-bromo-3,5-dimethoxyphenyl)methanol</strong> (0436) (compound 10, 1.95 g, 7.89 mmol) and NN-dimethylformamide (20 mL). The solution was cooled to 0 °C and sodium hydride (0.393 g of 60percent (w/w) in mineral oil, 10.3 mmol) was added and the reaction was stirred for 1 hour at room temperature. l-Bromo-2- methoxy ethane (0.89 mL, 9.47 mmol) was added and the reaction was stirred overnight at room temperature. The reaction was quenched with methanol and concentrated in vacuo. The residue was taken up in ethyl acetate and washed using water, then brine. The organic layer was dried using sodium sulfate, filtered and concentrated in vacuo. The resulting oil was purified on silica gel using ethyl acetate and hexanes as eluent. Product 2-Bromo-l,3- dimethoxy-5-((2-methoxyethoxy)methy)benzene (15, 2.22 g, 92percent yield) was isolated as a pale yellow oil. LC-MS: tR=2.11 min; m/z+ 23=327.0, 329.0. NM1HR (400 MHz, DMSO- d6) delta ppm 6.70 (s, 2 H) 4.48 (s, 2 H) 3.82 (s, 6 H) 3.53 - 3.62 (m, 2 H) 3.45 - 3.52 (m, 2 H) 3.26 (s, 3 H).
  • 32
  • [ 163622-50-2 ]
  • [ 6482-24-2 ]
  • 5-iodo-7-(2-methoxyethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine [ No CAS ]
  • 33
  • [ 7126-57-0 ]
  • [ 6482-24-2 ]
  • ethyl 4-formyl-1-(2-methoxyethyl)-1H-pyrrole-2-carboxylate [ No CAS ]
 

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