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Chemical Structure| 3647-69-6 Chemical Structure| 3647-69-6

Structure of 3647-69-6

Chemical Structure| 3647-69-6

4-(2-Chloroethyl)morpholine HCl

CAS No.: 3647-69-6

4.5 *For Research Use Only !

Cat. No.: A443032 Purity: 95%

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Product Details of [ 3647-69-6 ]

CAS No. :3647-69-6
Formula : C6H13Cl2NO
M.W : 186.08
SMILES Code : ClCCN1CCOCC1.[H]Cl
MDL No. :MFCD00012797
InChI Key :NBJHDLKSWUDGJG-UHFFFAOYSA-N
Pubchem ID :77210

Safety of [ 3647-69-6 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H312-H314-H317-H412
Precautionary Statements:P260-P264-P270-P272-P273-P280-P301+P310+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P333+P313-P362+P364-P405-P501
Class:8(6.1)
UN#:2923
Packing Group:

Computational Chemistry of [ 3647-69-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 48.5
TPSA ?

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

12.47 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

1.28
Log Po/w (WLOGP)?

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

0.98
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.

0.9
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

1.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.96

Water Solubility

Log S (ESOL):?

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

-1.67
Solubility 4.0 mg/ml ; 0.0215 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.

-1.14
Solubility 13.4 mg/ml ; 0.0722 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

-1.47
Solubility 6.28 mg/ml ; 0.0337 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.

-6.53 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

1.0
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)

1.94

Application In Synthesis of [ 3647-69-6 ]

* 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 [ 3647-69-6 ]

[ 3647-69-6 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 5791-00-4 ]
  • [ 3647-69-6 ]
  • 6-chloro-2-methyl-4-(2-morpholin-4-yl-ethyl)-4<i>H</i>-benzo[1,4]oxazin-3-one [ No CAS ]
  • 2
  • [ 3647-69-6 ]
  • sodium-<4-nitro-phenolate [ No CAS ]
  • [ 65300-53-0 ]
  • 3
  • [ 42017-89-0 ]
  • [ 3647-69-6 ]
  • 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropionic acid 2-(morpholin-4-yl)ethyl ester [ No CAS ]
  • 4
  • [ 1075-35-0 ]
  • [ 3647-69-6 ]
  • [ 1360566-43-3 ]
YieldReaction ConditionsOperation in experiment
Example 4Synthesis of CBX0024-(2-(5-chloro-2-methyl-lH-indol-l-yl)ethyl)morpholine[0157] To a solution of 2-chloroethylmorpholine HC1 (100 mg, 0.60 mmol) in 0.3 mL DMSO was added pulverized KOH (102 mg, 1.81 mmol), then after 10 min, a solution of 5- chloro-2-methylindole (134 mg, 0.72 mmol) in 0.2 mL DMSO was added and the reaction stirred at room temperature overnight. Additional 2-chloroethylmorpholine (22 mg, 0.12 mmol) and KOH (17 mg, 0.3 mmol) added and stirred overnight. The reaction mixture was partitioned between ¾0 and toluene, and the organic extract washed two times with ¾0, dried over MgS04, filtered, and concentrated in vacuo. The crude product was purified via silica gel chromatography using a gradient from 0 to 5% MeOH in (¾(¾ to give a final yield of 154 mg (0.55 mmol). XH NMR (500 MHz, CDC13, δ): 2.47 (s, 3H), 2.48-2.57 (m, 4H), 2.63 (t, J = 7.2 Hz, 2H), 3.73 (t, J = 4.4 Hz, 4H), 4.16 (t, J = 7.2 Hz, 2H), 6.20 (s, 1H), 7.1 1 (dd, J = 8.6 Hz, 1.7 Hz, 1H), 7.19 (d, J = 8.6 Hz, 1H), 7.50 (d, J = 1.5 Hz, 1H). 13C NMR (500 MHz, CDC13, δ): 12.88, 41.23, 54.13, 57.86, 66.95, 99.88, 109.78, 1 19.15, 120.64, 124.97, 129.18, 134.99, 138.03. MS m/z 279.3 [M + H]+.
  • 5
  • [ 100-02-7 ]
  • [ 3647-69-6 ]
  • [ 65300-53-0 ]
YieldReaction ConditionsOperation in experiment
91.1% With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2.5h; A mixture of 4-nitrophenol (11.13 g, 80 mmol), 4-(2-chloroethy)morpholine hydrochloride (15.64 g, 84 mmol) and Cs2CO3 (33.90 g, 104 mmol) were added in DMF (80 mL). The whole solution was stirred at 100 C for 2.5 h. The reaction mixture was allowed to cool at r.t and water (400 mL) was added. The mixture was stirred at 0 C for 30 minutes, filtered, dried to obtain compound 10. White solid. Yield: 91.1%; 1H NMR (400 MHz, CDCl3-d) δ: 8.19, (d, J =9.2 Hz, 2H), 6.96, (d, J =9.2 Hz, 2H), 4.20, (t, J =5.6 Hz, 2H), 3.74, (t, J =4.8 Hz, 4H), 2.84, (t, J =5.6 Hz, 2H), 2.59, (t, J =4.8 Hz, 4H). MS [ESI]: m/z, 253.2 [M+H]+.
90% With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 90℃; for 18h;Inert atmosphere; To a stirred mixture of 4-nitrophenol (21) (42 g, 0.30 mol) and 4-(2-chloroethyl)morpholine hydrochloride (56 g, 0.30 mol) in anhydrous DMF (400 mL) was added dry K2CO3 (104 g, 0.75 mol). The mixture was stirred under nitrogen at 80-90 C (bath temperature) for 3 h, then at 20 C overnight (15 h). The mixture was poured into ice-water (1.5 L) and stirred at 0 C for 1 h. The precipitated solid was filtered off, washed with water (6 * 100 mL) until the washes were colourless, then dried to give 22 as a pale yellow solid (68.4 g, 90%); mp 79-81 C [lit. mp 82-83 C (EtOAc/hexane) [21]]; δH (CDCl3) 8.23-8.17 (m, 2H), 6.99-6.94 (m, 2H), 4.20 (t, J = 5.7 Hz, 2H), 3.76-3.71 (m, 4H), 2.84 (t, J = 5.7 Hz, 2H), 2.62-2.55 (m, 4H); consistent with that reported [11]. [Found: C, 57.36; H, 6.44; N, 11.25.C12H16N2O4 requires C, 57.13; H, 6.39; N, 11.10].
82% With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 4h;Inert atmosphere; p-nitrophenol (4) 1.39g (10mmol) dissolved in anhydrous DMF, and then added the 5.29g (15mmol) of Cs2O3, 2-chloroethyl morpholine hydrochloride (10mmol), allow to warm at 100 C for 4 hours under the Nitrogen protection, and TLC monitors the reaction process. After completion of the reaction, the reaction solution was added to 100 mL of ice water and extracted three times with ethyl acetate. The organic phases were combined and washed successively with saturated sodium carbonate solution, water and saturated sodium chloride solution, and the final organic phase was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure then obtained compound 4-[2-(4-Nitrophenoxy) ethyl] morpholine (5) 1.84g, yield 82%.
With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2.5h;Inert atmosphere; General procedure: In 100 mL flask, 4-nitrophenol (1.39 g, 10 mmol) was dissolved in 20 mL anhydro-DMF. Then 3-chloro-N,N-dimethylpropan-1-amine hydrochloride (1.57 g, 10 mmol) and Cs2CO3 (5.29 g, 15 mmol) were added to the solution. Under N2, the mixture was heated to 100 C, and was reacted for 2.5 h. The mixture was filtered, and the filtrate was poured to ice water (200 mL). The aqueous phase was extracted by EtOAc (30 mL × 3). The combined organic phase was washed by Na2CO3 (10 mL × 4), water (10 mL × 2), saturated sodium chloride (15 mL). The organic layer was dried over Na2SO4, filtered, and distilled under vacuum to give the crude product.

  • 6
  • [ 5470-65-5 ]
  • [ 3647-69-6 ]
  • 4-(2-(3-bromo-4-nitrophenoxy)ethyl)morpholine [ No CAS ]
  • 7
  • [ 117011-70-8 ]
  • [ 3647-69-6 ]
  • C16H24N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;Reflux; <strong>[117011-70-8]4-aminophenoxyisobutyric acid</strong> (1.95 gm) (0.01 mol) was added to 2-chloroethylmorpholine hydrochloride (1.9 gm) (0.01 mol), and K2CO3 (2.376 gm) (0.02 mol) which was stirred and refluxed overnight. An insoluble portion remained in the mixture and 30 ml water was added and heating and stirring was continued for another 24 hrs. At this time, 1 gm dithionite was added and the solution was acidified with acetic acid. A light color solid was obtained. MW 307 C16H23N2O4
  • 8
  • [ 116632-23-6 ]
  • [ 3647-69-6 ]
  • 4-(2-(3-bromo-5-nitrophenoxy)ethyl)morpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
790 mg With potassium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 80℃; for 2h; 4-(2-Chloroethyl)morpholine, HCl (357 mg, 1.917 mmol) was added to a stirred suspension of <strong>[116632-23-6]3-bromo-5-nitrophenol</strong> (380 mg, 1.743 mmol), K2CO3 (964 mg, 6.97 mmol) and NaI (26.1 mg, 0.174 mmol) in N,N-dimethylformamide. Stirred at 80° C. for 2 h then the mixture was diluted with 20percent sodium chloride solution (50 mL) and extracted with ethyl acetate (3*50 mL). The combined organic phases were washed with saturated brine (50 mL), dried (MgSO4) and concentrated to yield the sub-title compound (790 mg) as a brown oil which was used in the next stage without further purification. LCMS m/z 331, 333 (M+H)+(ES+)
  • 9
  • [ 1198-14-7 ]
  • [ 3647-69-6 ]
  • 5-bromo-8-morpholinoethoxyquinoline [ No CAS ]
 

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Technical Information

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