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Chemical Structure| 16427-44-4 Chemical Structure| 16427-44-4

Structure of 16427-44-4

Chemical Structure| 16427-44-4

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Product Details of [ 16427-44-4 ]

CAS No. :16427-44-4
Formula : C4H10O4S
M.W : 154.19
SMILES Code : COCCOS(C)(=O)=O
MDL No. :MFCD02656401
InChI Key :BCKAHDGFNHDQST-UHFFFAOYSA-N
Pubchem ID :146293

Safety of [ 16427-44-4 ]

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

Computational Chemistry of [ 16427-44-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 32.48
TPSA ?

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

60.98 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.6
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

-0.5
Log Po/w (WLOGP)?

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

0.69
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.

-0.54
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

-0.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.16

Water Solubility

Log S (ESOL):?

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

-0.22
Solubility 93.6 mg/ml ; 0.607 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.

-0.31
Solubility 75.0 mg/ml ; 0.486 mol/l
Class?

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

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.85
Solubility 21.5 mg/ml ; 0.14 mol/l
Class?

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

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

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

No
Log Kp (skin permeation)?

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

-7.6 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

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

0.55

Medicinal Chemistry

PAINS?

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

0.0 alert
Brenk?

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

1.0 alert: heavy_metal
Leadlikeness?

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

No; 1 violation:MW<1.0
Synthetic accessibility?

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

2.9

Application In Synthesis of [ 16427-44-4 ]

* 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 [ 16427-44-4 ]

[ 16427-44-4 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 16427-44-4 ]
  • [ 10387-40-3 ]
  • [ 95966-75-9 ]
  • 2
  • [ 16427-44-4 ]
  • [ 627-43-0 ]
  • 3
  • [ 109-86-4 ]
  • [ 124-63-0 ]
  • [ 16427-44-4 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine; In dichloromethane; at 0 - 25℃; To a cooled solution (0 C.) of 2-methoxyethanol (0.8 mL) in CH2Cl2 (50 mL) and TEA (2 mL) is added dropwise methanesulfonyl chloride (1.3 mL). After 5 min, the bath is removed and the reaction mixture allowed to warm to RT and stir for 1 hour at which point it is washed with 1.0 N NaOH, brine, dried (MgSO4), and concentrated to give an oil. Yield quantitative. MS (ESI+) for C4H10O4S m/z 155.1 (M+H)+. To a solution of 2-methoxyethyl methanesulfonate (1.54 g) in 2-butanone (150 mL) is added cesium carbonate (6.50 g) and 3-fluoro-4-nitrophenol (1.52 g). The resulting mixture is refluxed for 19 hours, cooled, filtered, concentrated, and purified using silica gel chromatography (EtOAc/Heptanes). Yield 98%. 1H NMR (400 MHz, DMSO-d6) delta 7.95, 6.82, 6.67, 4.25, 3.92, 3.68, 3.33, 3.31. To a mixture of 2-methoxy-4-(2-methoxyethoxy)-1-nitrobenzene (2.0 g), 10% Pd/C (1.0 g) in MeOH (200 mL) is added conc. HCl (1.8 g). The resulting mixture is shaken at 40 psi H2 for 15 minutes. The mixture is filtered and crystallized from EtOH/Et2O to give 2-methoxy-4-(2-methoxyethoxy)aniline hydrochloride. Yield 76%. MS (ESI+) for C10H15NO3 m/z 198.1 (M+H)+. Example 156 (from 2-methoxy-4-(2-methoxyethoxy)aniline hydrochloride and 2-isocyanato-5-(trifluoromethyl)-1,3,4-thiadiazole) is prepared using Method B. Yield 50%. HRMS (ESI) calcd for C14H15N4O4SF3+H 393.0844, found 393.0838.
100% With triethylamine; In dichloromethane; at 0 - 25℃; To a cooled solution (0 C.) of 2-methoxyethanol (0.8 mL) in CH2Cl2 (50 mL) and TEA (2 mL) is added dropwise methanesulfonyl chloride (1.3 mL). After 5 minutes, the bath is removed and the reaction mixture allowed to warm to RT and stir for 1 hour, it is washed with 1.0 N NaOH, brine, dried (MgSO4), and concentrated to give an oil. Yield quantitative. MS (ESI+) for C4H10O4S m/z 155.1 (M+H)+. To a solution of 2-methoxyethyl methanesulfonate (1.54 g) in 2-butanone (150 mL) is added cesium carbonate (6.50 g) and 3-fluoro-4-nitrophenol (1.52 g). The resulting mixture is refluxed for 19 hours, cooled, filtered, concentrated, and purified using silica gel chromatography (EtOAc/Heptanes). Yield 98%. 1H NMR (400 MHz, DMSO-d6) delta 7.95, 6.82, 6.67, 4.25, 3.92, 3.68, 3.33, 3.31. To a mixture of 2-methoxy-4-(2-methoxyethoxy)-1-nitrobenzene (2.0 g), 10% Pd/C (1.0 g) in MeOH (200 mL) is added conc. HCl (1.8 g). The resulting mixture is shaken at 40 psi H2 for 15 minutes. The mixture is filtered and crystallized from EtOH/Et2O. Yield 76%. MS (ESI+) for C10H15NO3 m/z 198.1 (M+H)+. Example 313 (from from 2-methoxy-4-(2-methoxyethoxy)aniline hydrochloride and phenyl 5-methylisoxazol-3-ylcarbamate) is prepared using Method C, making non-critical changes. Yield 91%. HRMS (ESI) calcd for C15H19N3O5+H 322.1403, found 322.1394
Ca. 100% With triethylamine; In 1,2-dichloro-ethane; at 0 - 20℃; for 12h;Inert atmosphere; In a round-bottom flask containing a mixture of triethylamine (19.9 mL, 0.14 mol), 2-methoxyethanol (10.3 mL, 0.13 mol), and anhydrous dichloroethane (150 mL) at 0 C was added methanesulfonyl chloride (11.1 mL, 0.14 mol) over a period of 20 min. The mixture was warmed to ambient temperature under a nitrogen atmospheric pressure and stirred for 12 h. It was quenched by the addition of water and washed with water (2 × 150 mL), dilute hydrochloric acid (1 × 100 mL), and saturated sodium bicarbonate (1 × 100 mL) in sequence. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude brownish liquid was vacuum distilled at 120-130 C to afford 2-methoxyethylmethanesulfonate (17.9 g) in a nearly quantitative yield.
97% With triethylamine; In dichloromethane; at 0 - 20℃; 7.6 g (0.1 mol) of ethylene glycol monomethyl ether 24-1 was dissolved in 150 mL of anhydrous dichloromethane, 20 g of triethylamine was added, 0.1 M of a solution of methanesulfonyl chloride (0.11 mol) in dichloromethane was added dropwise at 0 C. After the addition was complete, the mixture was reacted at room temperature overnight, washed with water, dried and concentrated to obtain 14.9 g of ethylene glycol monomethyl ether protected with Ms 24-2, yield 97%.
96% With triethylamine; In dichloromethane; for 1h;Cooling with ice; An ice-cold solution of compound 79 (5 g, 65.7 mmol) and triethylamine (11 ml, 79 mmol) in DCM (150 mL) was treated with methanesulfonyl chloride (5.59 ml, 72.3 mmol) over 2 min. After 1 h the reaction was judged to be complete by TLC. Water was added and the organic extracts were washed sequentially with dilute HC1, saturated sodium bicarbonate, brine, then dried (MgS04), filtered and reduced. The product mesylate (9.4 g, 61 mmol, 96%>) was taken up in acetone (200 ml), then the potassium salt of toluene thiosulfmic acid (61 mmol) was added and the solution was stirred at 50C over 18 h. A thick white precipitate was observed to form. The mixture was filtered, reduced to an oil then extracted into DCM/water. The organicextracts were dried (MgS04), filtered and reduced. Column chromatography gave pure compound 80 as a colorless oil which crystallized on standing Rf = 0.3 (20% EA/hexane)
92% In dichloromethane; at 20℃; for 2h; 2-methoxyethanol (1, 6 ml, 0.075 mol) was dissolved in CH2Cl2 (102 ml). The solution was cooled on an ice bath (5 min) and then trimethylamine (20.7 ml, 0.15 mol) was added. Afterward, a solution of mesyl chloride (9.3 ml, 0.075 mol) in CH2Cl2 (18 ml) was added dropwise. The solution was kept at room temperature for 2 h. After this, the crude was poured onto a mixture of water/ice which contains HCl (20 ml). Then, the organic phase was decanted and the aqueous suspension extracted with CH2Cl2 (3 x 30 mL). Finally, the combined organic phases were washed with water (3 x 30 mL), dried with anhydrous MgSO4 and the solvent evaporated in a rotary evaporator. Product 2 was obtained as a yellow oil (92%, 0.069 mmol).
91% With triethylamine; In dichloromethane; for 2.5h; 2-Methoxyethanol (1a, 16 mL, 0.2 mol) was dissolved in dichloromethane (270 mL) in a 2 Lround-bottomed flask. The solution was kept in an ice bath for 15 min, and then triethylamine(55.2 mL, 0.4 mol) was added to the solution. Afterwards, a solution of methanesulfonyl chloride indichloromethane (0.32 mol in 48 mL) was added dropwise for 60 min to the initial reaction crude.After this addition, reaction was stirred at room temperature for another 90 min period. Then, thecrude was poured onto a water/ice mixture containing concentrated hydrochloric acid (50 mL), andthe organic layer was separated, washed three times with brine and dried with anhydrous MgSO4.Dichloromethane was eliminated in a rotary evaporator to give 1b as yellow oil (25.16 g, 0.18 mol, 91%yield). Spectroscopic data were coincident with those reported in the literature.
65% With trifluoroacetic acid; In dichloromethane; at 20℃; Methanesulfonyl chloride (15 g, 0.13 mol) was added to a mixture of 2-methoxy ethanol (10 g, 0.13 mol), triethylamine (26.5 g, 0.26 mol) and dichloromethane (150 g) at 0 C. After being stirred at room temperature overnight, water (100 g) was added to the reaction mixture. The layers were separated and the organic layer was concentrated in vacuo at room temperature. This gave 13.1 g (65%) of the title mesylate as an oil. 1H NMR analysis supports the stated structure. *Previously reported in Tetrahedron 1995,51, 4867-4890.
In dichloromethane; at 25℃; for 3h; Methanesulfonyl chloride (250 g), ethylene glycol monomethyl ether (97.8 g) and methylene chloride (587 mL) were added and the temperature was reduced to 0-5 C.(144 g) was slowly added and the reaction was allowed to proceed at 25 C for 3 hours. TLC indicated that the reaction was completed and 1360 g of ice water was added,And the layers were separated. The aqueous layer was extracted with dichloromethane (645 mL X2), the methylene chloride layers were combined, washed with 635 g of water,20.5 glmol / L hydrochloric acid (pH
With triethylamine; In dichloromethane; at 10℃; for 1.5h;Cooling with ice; B1,190 mL of solvent dichloromethane,40 mL of ethylene glycol methyl ether and 210 mL of triethylamine (TEA) were added to a 1000 mL four-necked flask in that order.39 mL of methanesulfonyl chloride and 40 mL of methylene chloride (dilution) were added to a 250 mL constant pressure dropping funnel;The four-necked flask was placed in an ice-water bath,The dropping reaction was started,Adjust the drip rate of 1.5ml / min,The reaction temperature was controlled to 10 C or lower,After completion of the dropwise addition,Stirring 1.5h stop,Drop process system appears white mist,Four-mouth flask with yellow-white solid attached;B2, comprising the steps of:evaporation:The reactants obtained in step b1 were subjected to rotary evaporation under reduced pressure using a reaction apparatus consisting of a circulating vacuum pump and a rotary evaporator,The temperature of the rotary evaporator was set at 50 C,Solvent dichloromethane and acid-binding agent triethylamine gradually steamed out,To be no dripping,Continue to rotate evaporation 20min washing:The evaporated material was dissolved in about 100 ml of dichloromethane,Followed by suction filtration,The filtrate contains the reaction product,The filtrate was collected,Discard the cake triethylamine salt;The filtrate was pickled 5 times,Using a mixed solution of hydrochloric acid and water in a volume ratio of 1: (3 to 5)The remaining triethylamine in the filtrate was removed,The upper layer of the separatory funnel was a hydrochloric acid solution in which triethylamine salt was dissolved,Abandoned,The lower layer is a methylene chloride solution in which the reaction product is dissolved,collect;The methylene chloride solution was washed with water 5 times,The residual hydrochloric acid was removed,Until the water layer close to neutral,The upper layer of the separatory funnel was an aqueous layer containing hydrochloric acid,Abandoned,The lower layer is a methylene chloride solution which dissolves the reaction product,collect;dry:To the dichloromethane solution was added anhydrous MgSO4 overnight,The MgSO4 was filtered off,Then subjected to rotary evaporation,Methylene chloride was distilled off;Vacuum distillation:The material left by the rotary evaporation was distilled under reduced pressure,The distillate was collected at 98 & lt; 0 &That is, ethylene glycol methyl ether methyl sulfonate,Its structure is as follows:Sealed into the dryer to save reserve;
With triethylamine; In toluene; at 20℃; for 0.5h;Cooling with ice; Dissolve 5g of 2-methoxyethanol in 10ml of toluene.Add 5.6 ml of triethylamine,5.6 ml of methanesulfonyl chloride was added slowly under ice bath.A large amount of white solid precipitated during the addition.After the addition, the ice bath was removed.Stir at room temperature for 30 min.TLC showed that the reaction of raw materials was completed.After the reaction solution is evaporated,Add 30ml of ethyl acetate and 30ml of water,Divide the water layer,After the organic layer is dry,concentrate,The crude 2-methoxy ethoxy carboxylic acid ester was obtained.Take 200mg crude product dissolved in 10ml DMF,230 mg of 4-chloro-7-hydroxyquinoline was added in succession.358mg cesium carbonate,After putting it in a 50C oil bath for 3 hours,TLC showed that the reaction of the raw materials was completed.After stopping the reaction,After the reaction liquid cools,The DMF is distilled off under reduced pressure.To the residue was added 30 ml of ethyl acetate and 30 ml of water.Extraction and separation of water layer,The organic layer is washed 3 times.30ml each time.After the organic layer is dry,concentrate,The crude 4-chloro-7-methoxyethoxyquinoline (off-white solid, quantitative yield) was obtained.

  • 4
  • [ 16427-44-4 ]
  • [ 1666-13-3 ]
  • [ 65275-38-9 ]
  • 5
  • [ 86-73-7 ]
  • [ 16427-44-4 ]
  • [ 57722-05-1 ]
  • 6
  • [ 16427-44-4 ]
  • [ 109-86-4 ]
  • 7
  • [ 16427-44-4 ]
  • [ 120-80-9 ]
  • [ 33332-53-5 ]
  • 8
  • [ 16427-44-4 ]
  • [ 160978-44-9 ]
  • meso-20,21-bis(2-methoxyethoxy)-1,4,7,10,13-pentaoxa<13.2>(1,2)benzenophane [ No CAS ]
  • 9
  • [ 16427-44-4 ]
  • rac-20,21-dihydroxy-1,4,7,10,13-pentaoxa<13.2>(1,2)benzophane [ No CAS ]
  • rac-20,21-bis(2-methoxyethoxy)-1,4,7,10,13-pentaoxa<13.2>(1,2)benzenophane [ No CAS ]
  • 10
  • [ 16427-44-4 ]
  • [ 160978-45-0 ]
  • meso-23,24-bis(2-methoxyethoxy)-1,4,7,10,13,16-hexaoxa<16.2>(1,2)benzenophane [ No CAS ]
  • 11
  • [ 20462-00-4 ]
  • [ 16427-44-4 ]
  • 2-(2-Methoxy-ethyl)-[1,3]dithiane-2-carboxylic acid ethyl ester [ No CAS ]
  • 12
  • [ 16427-44-4 ]
  • [ 148528-45-4 ]
  • [ 169616-09-5 ]
  • 13
  • [ 16427-44-4 ]
  • [ 95-13-6 ]
  • C9H7-3-CH2CH2OMe [ No CAS ]
  • 15
  • [ 16427-44-4 ]
  • [ 120-07-0 ]
  • [ 484679-02-9 ]
YieldReaction ConditionsOperation in experiment
42% With sodium hydride; In acetonitrile; for 34h;Inert atmosphere; Reflux; N,N-phenyldiethanolamine (3, 3.6 g, 0.02 mol) was dissolved in dry acetonitrile (120 ml) in a two neck round-bottomed flask that was purged with argon. Then, sodium hydride (1.44 g, 0.06 mol) was slowly added to the solution in order to deprotonate compound 3. Afterward, a solution of 2 (7.7 g, 0.05 mol) in acetonitrile (20 ml) was added dropwise under argon and the crude was stirred at reflux for 34 h. Then, the crude was filtered off and acetonitrile was evaporated. The crude was purified by column chromatography using aluminum oxide as stationary phase and hexane-ethyl acetate 7:3 v/v as eluent. Product 4 was isolated as yellow oil (42%, 0.0084 mol).
  • 16
  • [ 16427-44-4 ]
  • (+)-trans-2-<2-(2-methoxyethoxy)ethoxy>cyclohexan-1-ol [ No CAS ]
  • trans-2-[[2-(methoxy)ethoxy]ethoxy]-1-[(2-methoxy)ethoxy]cyclohexane [ No CAS ]
  • 17
  • [ 16427-44-4 ]
  • trans-2-(9-methoxy-1,4,7-trioxanonyl)cyclohexanol [ No CAS ]
  • (1R,2R)-1-(2-Methoxy-ethoxy)-2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-cyclohexane [ No CAS ]
  • 18
  • [ 16427-44-4 ]
  • N-(2-phenylethyl)-4,13-diaza-18-crown-6 [ No CAS ]
  • 7-(2-methoxy-ethyl)-16-phenethyl-1,4,10,13-tetraoxa-7,16-diaza-cyclooctadecane [ No CAS ]
  • 19
  • [ 16427-44-4 ]
  • [ 394-41-2 ]
  • [ 625119-89-3 ]
YieldReaction ConditionsOperation in experiment
98% With caesium carbonate; In butanone; for 19h;Heating / reflux; To a cooled solution (0 C.) of 2-methoxyethanol (0.8 mL) in CH2Cl2 (50 mL) and TEA (2 mL) is added dropwise methanesulfonyl chloride (1.3 mL). After 5 min, the bath is removed and the reaction mixture allowed to warm to RT and stir for 1 hour at which point it is washed with 1.0 N NaOH, brine, dried (MgSO4), and concentrated to give an oil. Yield quantitative. MS (ESI+) for C4H10O4S m/z 155.1 (M+H)+. To a solution of <strong>[16427-44-4]2-methoxyethyl methanesulfonate</strong> (1.54 g) in 2-butanone (150 mL) is added cesium carbonate (6.50 g) and 3-fluoro-4-nitrophenol (1.52 g). The resulting mixture is refluxed for 19 hours, cooled, filtered, concentrated, and purified using silica gel chromatography (EtOAc/Heptanes). Yield 98%. 1H NMR (400 MHz, DMSO-d6) delta 7.95, 6.82, 6.67, 4.25, 3.92, 3.68, 3.33, 3.31. To a mixture of 2-methoxy-4-(2-methoxyethoxy)-1-nitrobenzene (2.0 g), 10% Pd/C (1.0 g) in MeOH (200 mL) is added conc. HCl (1.8 g). The resulting mixture is shaken at 40 psi H2 for 15 minutes. The mixture is filtered and crystallized from EtOH/Et2O to give 2-methoxy-4-(2-methoxyethoxy)aniline hydrochloride. Yield 76%. MS (ESI+) for C10H15NO3 m/z 198.1 (M+H)+. Example 156 (from 2-methoxy-4-(2-methoxyethoxy)aniline hydrochloride and 2-isocyanato-5-(trifluoromethyl)-1,3,4-thiadiazole) is prepared using Method B. Yield 50%. HRMS (ESI) calcd for C14H15N4O4SF3+H 393.0844, found 393.0838.
98% With caesium carbonate; In butanone; for 19h;Heating / reflux; To a cooled solution (0 C.) of 2-methoxyethanol (0.8 mL) in CH2Cl2 (50 mL) and TEA (2 mL) is added dropwise methanesulfonyl chloride (1.3 mL). After 5 minutes, the bath is removed and the reaction mixture allowed to warm to RT and stir for 1 hour, it is washed with 1.0 N NaOH, brine, dried (MgSO4), and concentrated to give an oil. Yield quantitative. MS (ESI+) for C4H10O4S m/z 155.1 (M+H)+. To a solution of <strong>[16427-44-4]2-methoxyethyl methanesulfonate</strong> (1.54 g) in 2-butanone (150 mL) is added cesium carbonate (6.50 g) and 3-fluoro-4-nitrophenol (1.52 g). The resulting mixture is refluxed for 19 hours, cooled, filtered, concentrated, and purified using silica gel chromatography (EtOAc/Heptanes). Yield 98%. 1H NMR (400 MHz, DMSO-d6) delta 7.95, 6.82, 6.67, 4.25, 3.92, 3.68, 3.33, 3.31. To a mixture of 2-methoxy-4-(2-methoxyethoxy)-1-nitrobenzene (2.0 g), 10% Pd/C (1.0 g) in MeOH (200 mL) is added conc. HCl (1.8 g). The resulting mixture is shaken at 40 psi H2 for 15 minutes. The mixture is filtered and crystallized from EtOH/Et2O. Yield 76%. MS (ESI+) for C10H15NO3 m/z 198.1 (M+H)+. Example 313 (from from 2-methoxy-4-(2-methoxyethoxy)aniline hydrochloride and phenyl 5-methylisoxazol-3-ylcarbamate) is prepared using Method C, making non-critical changes. Yield 91%. HRMS (ESI) calcd for C15H19N3O5+H 322.1403, found 322.1394
YieldReaction ConditionsOperation in experiment
The following specific compounds of the formula (XVII) may be mentioned: 2-Methoxyethyl methanesulphonate 2-Ethoxyethyl methanesulphonate 2-Ethoxyethyl p-toluenesulphonate
  • 21
  • [ 16427-44-4 ]
  • [ 584-08-7 ]
  • [ 81801-12-9 ]
  • N-(2-((2-hydroxy-3-(4-(2-methoxyethoxy)-phenoxy)propyl)amino)ethyl)-4-morpholinecarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In dichloromethane; acetonitrile; EXAMPLE 9 (Method e) 17 g of N-(2-((2-hydroxy-3-(4-hydroxyphenoxy)propyl)amino)ethyl)-4-morpholinecarboxamide and 6 g of 2-methoxyethyl mesylate and 6.9 g of K2 CO3 was refluxed in acetonitril for 20 h. The resulting mixture was filtered and evaporated. The residue was dissolved in methylene chloride and extracted with water containing 1 g of NaOH, then with water and then dried over Na2 SO4, filtered and evaporated. The residue was crystallized from ethyl acetate yielding N-(2-((2-hydroxy-3-(4-(2-methoxyethoxy)phenoxy)propyl)amino)ethyl)-4-morpholinecarboxamide. Melting point 69 C. (base).
  • 22
  • [ 16427-44-4 ]
  • [ 141699-55-0 ]
  • N-tert-Butoxycarbonyl-3-(2-methoxyethoxy)azetidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; Reference example 4 N-tert-Butoxycarbonyl-3-(2-methoxyethoxy)azetidine To a suspension of 0.25 g of 60% sodium hydride in 5 ml of dried N,N-dimethylformamide, a solution of 1.00 g of N-tert-butoxycarbonyl-3-azetidinol in 3 ml of dried N,N-dimethylformamide was added under stirring at room temperature. The mixture was stirred at room temperature for 30 minutes, then added dropwise with a solution of 0.98 g of <strong>[16427-44-4]2-methoxyethyl methanesulfonate</strong> in 2 ml of dried N,N-dimethylformamide, and stirred at the same temperature for 4 hours. The reaction solution was poured into ice water, and extracted with ethyl acetate. The extract was washed successively with water and saturated brine, and dried over sodium sulfate, and then the solvent was evaporated under reduced pressure. Theresidue was purified by column chromatography (silica gel, ethyl acetate: n-heptane = 1: 3) to obtain 0.67 g of a colorless liquid. NMR spectrum (DMSO-d6) delta ppm: 1.37(9H,s),3.25(3H,s),3.41-3.45(2H,m),3.46-3.49(2H,m),3.64(2H,dd,J=9,4Hz),3.98(2H,d d,J=9,6.5Hz),4.21-4.26(1H,m) IR spectrum nu (liq.) cm-1: 1706
  • 23
  • [ 16427-44-4 ]
  • [ 58-61-7 ]
  • [ 303197-30-0 ]
  • [ 1062491-29-5 ]
  • [ 1062491-27-3 ]
  • [ 168427-74-5 ]
  • 24
  • [ 16427-44-4 ]
  • [ 58-61-7 ]
  • [ 303197-30-0 ]
  • [ 1062491-29-5 ]
  • [ 168427-74-5 ]
  • 25
  • [ 16427-44-4 ]
  • [ 2096-10-8 ]
  • [ 256224-02-9 ]
  • [ 847647-19-2 ]
  • [ 256224-13-2 ]
  • 26
  • [ 948592-54-9 ]
  • [ 16427-44-4 ]
  • [ 1079402-29-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl acetamide; at 100℃; for 10h; Methanesulfonic acid 2-methoxyethyl ester (70.5 mg, 0.50 mmol) and 2-[2-chloro-5- hydroxyphenyl]-4,4,5,5-tetramethyl-[1 ,3,2]-dioxaborolane (Preparation 66, 100 mg, 0.42 mmol) were stirred together in N,N-dimethylacetamide (4 ml). Potassium carbonate (58 mg, 0.42 mmol) was added and the resultant solution was heated to 1000C for 10 hours. The reaction mixture was cooled then quenched with water (10 ml) and extracted with ethylacetate (10 ml).The organic layer was dried over anhydrous MgSO4 (s), filtered and evaporated in vacuo Xo give crude title compound. Material taken on without further purification.
  • 27
  • [ 16427-44-4 ]
  • [ 1133-80-8 ]
  • [ 649724-44-7 ]
YieldReaction ConditionsOperation in experiment
To a solution of 2-bromofluorene (2.45 g, 10 mmol) in tetrahydrofuran (dry, 75 ml) was added potassium t-butoxid (3.36 g, 30 mmol), giving a deep orange solution. The mixture was stirred at ambient temperature for 10 min and added 2-methoxyethyl mesylate in tetrahydrofuran dropwise. Exothermic reaction was observed. Stirring was continued at ambient temperature for overnight to give an orange solution. At the end of the reaction, it was diluted with water (150 ml). The products extracted with ethylacetate (30 ml) and washed with water. Organic layer was dried over magnesium sulfate and concentrated in vacuuo to afford the crude product. It was purified by preparative thin layer chromatography (silica gel, [RF =] 0.3 using hexane-EtOAc/3: 2 as eluent) to give 2-bromo-9, 9-dimethoxyethylfluorene (3.3 g).
  • 28
  • [ 16427-44-4 ]
  • [ 4733-50-0 ]
  • [ 75942-40-4 ]
  • 29
  • [ 895152-66-6 ]
  • [ 16427-44-4 ]
  • (1-(2-methoxyethyl)-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone [ No CAS ]
  • 30
  • [ 1002352-24-0 ]
  • [ 16427-44-4 ]
  • [ 1251581-98-2 ]
YieldReaction ConditionsOperation in experiment
65% To a solution of the carbamate 22b (3.8 g, 1 eq) in NMP (20 mL) at RT under N2 is added NaH (660 mg, 1.2 eq). The mixture is stirred at RT for 15 min and a solution of 2-methoxyethyl mesylate/NMP (2.5 g, 1.2 eq/5 mL) is added. The mixture is stirred at RT for 10 min then heated at 90 C. for 1.5 h. The mixture is poured into water then extracted with EtOAc (2×). The organic extract is washed with brine, dried over MgSO4, filtered and concentrated. The residue is purified by flash chromatography on silica gel (10-30% EtOAc/Hex) to give compound 22c (3.0 g, 65%).
  • 31
  • [ 905306-05-0 ]
  • [ 16427-44-4 ]
  • [ 1259519-61-3 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; for 12h; A solution of 4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-ol (2.9 g, O.Olmol), 2-methoxyethyl methane sulfonate (4.6 g, 0.03 mol, 3 equiv),and cesium carbonate (9.9 g, 0.03 mol, 3 equiv) in DMF(IOO ml) was heated to 60 0C for 12 hours. The reaction mixture was cooled to room temperature and poured into cold water, the solid was filtrated and dried to give 1.5g product. MS (ESI) m/z: 350 (M+l).
  • 32
  • [ 616-47-7 ]
  • [ 16427-44-4 ]
  • [ 637739-85-6 ]
YieldReaction ConditionsOperation in experiment
96% In benzene; at 80℃; for 12h; Example 1-(2); Synthesis of 1-ethylene Glycol Monomethyl Ether 3-methylimidazolium Methanesulfonate; 1-Methylimidazole (40 g) and ethylene glycol monomethyl ether methanesulfonate (90 g) were stirred at 80 C. for 12 hours in benzene in a 500 mL two-bulb flask equipped with a reflux condenser. After the reaction was completed, the product was washed several times with ethyl acetate or diethyl ether to remove unreacted 1-methylimidazole and ethylene glycol monomethyl ether methanesulfonate. The remaining ionic liquid was dried at 60 C. in vacuum (yield: 96%).
  • 33
  • [ 616-47-7 ]
  • [ 109-86-4 ]
  • [ 124-63-0 ]
  • [ 16427-44-4 ]
  • [ 35487-17-3 ]
YieldReaction ConditionsOperation in experiment
98% In dichloromethane; at 10 - 20℃; for 4h; Example 1-(1); Synthesis of Ethylene Glycol Monomethyl Ether Methanesulfonate; 1-Methylimidazole (50 g) and methanesulfonyl chloride (66 g) were mixed in dichloromethane in a 500 mL two-bulb flask. After adding ethylene glycol monomethyl ether (42 g) dropwise at 10 C., the mixture was stirred at room temperature for 4 hours. After the reaction was completed, water was added. After stirring for 10 minutes, the solvent layer in which the product was dissolved was separated from the aqueous layer in which the byproduct was dissolved. The product was yielded by removing the solvent at room temperature using an evaporator (yield: 98%), and the byproduct 1-methylimidazolium chloride was recovered as 1-methylimidazole using 40 wt % NaOH aqueous solution and used again (yield: 95%).
  • 34
  • [ 16427-44-4 ]
  • [ 1249712-42-2 ]
  • [ 135530-70-0 ]
  • 35
  • [ 16427-44-4 ]
  • 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate [ No CAS ]
  • [ 1415991-70-6 ]
YieldReaction ConditionsOperation in experiment
Example 415-[2-fluoro-4-(lH-tetrazol-l-yl)phenyl]-2-[l-(2-methoxyethyl)piperidin-4- yl]benzo [rf]oxazole : [285] 5-[2-fluoro-4-(lH-tetrazol-l-yl)phenyl]-2-(piperidin-4-yl)benzo[ ]oxazole 2,2,2- trifluoroacetate (30 mg, 0.06 mmol) was dissolved in DMF (2 ml) and added K2CO3 (40 mg, 0.29 mmol) and stirred the mixture at rt for 15 mins. To this mixture added <strong>[16427-44-4]2-methoxyethyl methanesulfonate</strong> (45 mg, 0.29 mmol) and stirred at rt for 17 h. Work up (EtOAc/H20) followed by purification by column chromatography on 60-120 mesh silicagel using a gradient mixture of DCM and MeOH (98:2) as eluent afforded the titled compound (90 mg) as a brown solid (15 mg). M.P.: 148-152 C. MS (m/z): 423.3 [M+H]+.
 

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