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Structure of 4497-04-5

Chemical Structure| 4497-04-5

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Product Details of [ 4497-04-5 ]

CAS No. :4497-04-5
Formula : C7H13NO3
M.W : 159.18
SMILES Code : O=C(O)CCN1CCOCC1
MDL No. :MFCD02089311
InChI Key :YUYHRSGXZZVNMS-UHFFFAOYSA-N
Pubchem ID :410813

Safety of [ 4497-04-5 ]

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

Computational Chemistry of [ 4497-04-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 0.86
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 43.32
TPSA ?

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

49.77 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.58
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

-2.89
Log Po/w (WLOGP)?

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

-0.59
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.

-0.5
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

0.35
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.41

Water Solubility

Log S (ESOL):?

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

1.19
Solubility 2480.0 mg/ml ; 15.6 mol/l
Class?

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

Highly soluble
Log S (Ali)?

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

2.4
Solubility 40200.0 mg/ml ; 253.0 mol/l
Class?

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

Highly 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

-0.24
Solubility 92.2 mg/ml ; 0.579 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.

-9.32 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

0.0 alert: heavy_metal
Leadlikeness?

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

No; 1 violation:MW<1.0
Synthetic accessibility?

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

1.58

Application In Synthesis of [ 4497-04-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 4497-04-5 ]

[ 4497-04-5 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 110-91-8 ]
  • [ 57-57-8 ]
  • [ 4497-04-5 ]
  • 2
  • [ 33611-43-7 ]
  • [ 4497-04-5 ]
YieldReaction ConditionsOperation in experiment
89% With potassium hydroxide; In ethanol; The starting material was prepared as follows: Potassium hydroxide (485 mg, 8.6mmol) was added to a solution of methyl 3-morpholinopropionate (1 g, 5.7 mmol) in ethanol (20 ml) and the mixture stirred for 2 hours at 80° C. The solution was allowed to cool and adjusted to pH1 with 6M hydrochloric acid. Insoluble material was removed by filtration and the volatiles removed from the filtrate by evaporation. The resulting oil was triturated with ether, the solid product collected by filtration, washed with methylene chloride and dried under vacuum to give 3-morpholinopropionic acid (993 mg, 89percent) as a white solid. 1H NMR Spectrum: (DMSOd6; CF3COOD) 2.83(t, 2H); 3.13(t, 2H); 3.36(t, 2H); 3.46(d, 2H); 3.73(t, 2H); 3.97(d, 2H) MS-ESI: 159 [MH]+
Example 17 Preparation of [3-(2-morpholin-4-yl-ethyl)-imidazo[1,5-a]pyridin-1-yl]-naphthalen-1-yl-methanone To a solution of methyl 4-morpholinepropionate (5.0 g, 28.9 mmol) in MeOH (25 mL) was added 2N NaOH (17.3 mL, 34.6 mmol). The mixture was stirred for 1 h then concentrated in vacuo. The residue was suspended in dichloromethane (125 mL) and DMF (30 muL) was added followed by oxalylchloride (10 mL, 115.6 mmol). The mixture was allowed to stir for 2 h. then concentrated in vacuo. The resulting solid was added portion-wise to a solution of 2-(aminomethyl)pyridine (2.88 mL, 28.2 mmol) and triethylamine (9.0 mL, 64.86 mmol) in dichloromethane (200 mL). The mixture was stirred at ambient temperature for 1 h. then washed with water (300 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to yield 3-morpholin-4-yl-N-pyridin-2-ylmethyl-propionamide (5.56 g, 77percent).
  • 4
  • [ 4497-04-5 ]
  • [ 134805-50-8 ]
  • (2S,3R,4R,5S)-2,5-bis<N-<N-<3-(4-morpholinyl)propanoyl>valinyl>amino>-3,4-dihydroxy-1,6-diphenylhexane [ No CAS ]
  • 5
  • [ 110-91-8 ]
  • [ 292638-85-8 ]
  • [ 4497-04-5 ]
  • 6
  • [ 4497-04-5 ]
  • 3-morpholino-1-hydroxypropylidenebisphosphonic acid [ No CAS ]
  • 7
  • tert-butyl 3-morpholinopropanoate [ No CAS ]
  • [ 4497-04-5 ]
YieldReaction ConditionsOperation in experiment
B. 3-(4-Morpholinyl)propanoic Acid A solution of the resultant compound of Example 202A (8.35 g, 48.3 mmol) in 60 ml of dioxane was treated with 40 ml of water and 19.3 ml (58 mmol) of 3N aqueous NaOH. After being stirred for 4 h, the solution was treated with 58 ml (58 mmol) of 1N aqueous HCl and concentrated in vacuo to provide the crude desired compound.
beta-Morpholino-propionic acid (used for preparing compound No. 32) NMR (60 MHz, delta values in CD3 OD): 2.45 (2H, t, J=6 Hz, --COCH2 --) STR31 3.83 (4H, m, --CH2 OCH2 --)
  • 9
  • [ 4497-04-5 ]
  • [ 3282-30-2 ]
  • C12H21NO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% Example 7; 4-[5-amino- l-(2,6-difluoro-benzoyl)- lH-[ 1 ,2,4]triazol-3- ylamino]-N-(3-morpholin-4-yl-propionyl)-benzenesulfonamide(Cpd 7); 7a; Using the mixed anhydride formation procedure, 1.9 g (100 percent) of Compound7a was generated from morpholinylpropionic acid (1.25 g) and pivaloyl chloride (1.05 g). 1H NMR (300 MHz, CDCl3) delta 3.68 (m, 4 H), 2.75 (t, 2 H), 2.65 (t, 2 H), 2.45 (m, 4 H), 1.21 (s, 9 H).
  • 10
  • [ 4497-04-5 ]
  • [ 444904-20-5 ]
  • N-[(1R,4S,5S,7R)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]non-7-yl]-3-(morpholin-4-yl)propionamide [ No CAS ]
  • 11
  • [ 931112-72-0 ]
  • [ 4497-04-5 ]
  • N-(5-chloro-3-(4-(2-chloro-5-(trifluoromethyl)phenyl)-5-cyano-6-oxo-1,6-dihydropyridin-2-yl)-2-hydroxybenzyl)-N-methyl-3-(4-morpholinyl)propanamide [ No CAS ]
  • 12
  • [ 952658-86-5 ]
  • [ 4497-04-5 ]
  • [ 557-21-1 ]
  • C23H22N6O2 [ No CAS ]
  • 13
  • [ 4497-04-5 ]
  • 4-[5-amino-1-(2,6-difluoro-benzoyl)-1H-[1,2,4]triazol-3-ylamino]-N-(3-morpholin-4-ylpropionyl)benzenesulfonamide [ No CAS ]
  • 18
  • [ 4497-04-5 ]
  • [ 186668-40-6 ]
  • homo-camptothecin-20-O ester of N-morpholine propionic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; at 20℃; for 20.16h; [[0158]] B. Homocamptothecin-20-O ester of N-morpholine propionic acid The target molecule is synthesized using the above procedure for this example. The flask is charged with homocamptothecin [(HCPT)] (20 mg,. 05 mmol) and then 7 mL of dry chloroform. The solution is allowed to stir for 10 minutes at ambient temperature. [1- (3-] [DIMETHYLAMINO-PROPYL)-3-ETHYL-CARBODIIMIDE] hydrochloride (EDCI) (61 mg, 0.31 mmol), 4- (dimethylamino) pyridine (DMAP) (12 mg, . 12 mmol) and N-morpholine propionic acid (23 mg, . 15 mmol) is added. The reaction is allowed to stir for 20 hours at ambient temperature and worked up according to the procedure.
 

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