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Structure of 783350-37-8

Chemical Structure| 783350-37-8

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Product Details of [ 783350-37-8 ]

CAS No. :783350-37-8
Formula : C10H17NO5
M.W : 231.25
SMILES Code : O=C([C@H]1N(C(OC(C)(C)C)=O)CCOC1)O
MDL No. :MFCD04114904
InChI Key :KVXXEKIGMOEPSA-ZETCQYMHSA-N
Pubchem ID :1512537

Safety of [ 783350-37-8 ]

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

Computational Chemistry of [ 783350-37-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 4
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 59.45
TPSA ?

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

76.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.96
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

0.37
Log Po/w (WLOGP)?

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

0.33
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.

-0.07
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

-0.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.5

Water Solubility

Log S (ESOL):?

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

-1.24
Solubility 13.2 mg/ml ; 0.0572 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.

-1.53
Solubility 6.78 mg/ml ; 0.0293 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

-0.12
Solubility 177.0 mg/ml ; 0.764 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.

-7.45 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

0.0
Bioavailability Score?

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

0.56

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)

3.13

Application In Synthesis of [ 783350-37-8 ]

* 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 [ 783350-37-8 ]

[ 783350-37-8 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 24424-99-5 ]
  • [ 106825-79-0 ]
  • [ 783350-37-8 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 1h; INTERMEDIATE 33: MORPHOLINE-3 (S), 4-DICARBOXYLIC ACID 4- tert-butyl ester [00157] A suspension of morpholine-3 (S)-CARBOXYLIC acid (2.00 g, 15.3 mmol) in DMF (75 ml) was stirred at RT. Triethylamine (7.47 ml, 53.6 mmol) and di-tert-butyl dicarbonate (BOC20, 4.02 g, 18.4 mmol) were added. The suspension was stirred at RT for one hour, during which time the reaction formed a clear yellow solution. The solution was concentrated to a reduced volume (-25 ml) and diluted with water (15 ml) and IN HC1 (15 ml). The mixture was poured into a separatory funnel, diluted further with water (100 ml) and brine (100 ml), and extracted with ET20 (3 x 100 ml). The organic layer was washed with brine, dried, filtered and concentrated to yield a white solid. The solid, which contained excess BOC20, was dissolved in ET20 (500 ml) and extracted with IN NaOH (3 x 100 ml). The aqueous layer was acidified with 6N HC1 to approximately a pH of 2, then extracted quickly with ET20 (3 x 100 ml). The ET20 layer was dried, filtered and concentrated to yield white solid (3.07 g). H-NMR (300 MHz, DMSO-d6): 5 12.95 (br s, 1); 4.34-4. 30 (m, 1); 4.18-4. 10 (m, 1); 3.83-3. 74 (m, 1); 3.59-3. 51 (m, 2); 3.39-3. 32 (m, 1); 3.21-2. 95 (m, 1); 1.41-1. 36 (m, 9). NH40Ac standard conditions. ELSD Rf = 1.08 min. M-H = 230.
With triethylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 1h; Intermediate 33: morpholine-3(S), 4-dicarboxylic acid 4-tert-butyl ester A suspension of <strong>[106825-79-0]morpholine-3(S)-carboxylic acid</strong> (2.00 g, 15.3 mmol) in DMF (75 ml) was stirred at RT. Triethylamine (7.47 ml, 53.6 mmol) and di-tert-butyl dicarbonate (BOC2O, 4.02 g, 18.4 mmol) were added. The suspension was stirred at RT for one hour, during which time the reaction formed a clear yellow solution. The solution was concentrated to a reduced volume (25 ml) and diluted with water (15 ml) and 1N HCl (15 ml). The mixture was poured into a separatory funnel, diluted further with water (100 ml) and brine (100 ml), and extracted with Et2O (3*100 ml). The organic layer was washed with brine, dried, filtered and concentrated to yield a white solid. The solid, which contained excess BOC2O, was dissolved in Et2O (500 ml) and extracted with 1N NaOH (3*100 ml). The aqueous layer was acidified with 6N HCl to approximately a pH of 2, then extracted quickly with Et2O (3*100 ml). The Et2O layer was dried, filtered and concentrated to yield white solid (3.07 g). 1H-NMR (300 MHz, DMSO-d6): delta 12.95 (br s, 1); 4.34-4.30 (m, 1); 4.18-4.10 (m, 1); 3.83-3.74 (m, 1); 3.59-3.51 (m, 2); 3.39-3.32 (m, 1); 3.21-2.95 (m, 1); 1.41-1.36 (m, 9). NH4OAc standard conditions. ELSD Rf=1.08 min. M-H=230.
With sodium hydrogencarbonate; In 1,4-dioxane; water; at 20℃; for 16h; A mixture of (S)morphoine-3-carboxyic acid (1.0 g, 7.63 mmo) and Boc2O (1.77 m, 763 mmoD in 10% NaHCO3 so?ution in water (10 m, 7.63 mmofl and 1,4dioxane (10 m) was stirred at RT for 16h. Water and AcOEt were added to mixture and phases were separated. The aqueous ayer was acidified to pH 34 with IM aqueous citric acid (12 m) and extracted 3 times with AcOEt. The organic ayer was washed with brine, dried over a phase separator cartridge (ST), the sovent was evaporated and the residue dried under vacuum to afford (S)-4(tert-butoxycarbony)morphoHne-3-carboxyHc acid Mz = 232 [M+Hj+, Rt = 070 mm (UPLC Method B2), 1H NMR (400 MHz. DMSO-d5) 6ppm: 12.94 (bs, IH), 4.32 (dd, IH), 4.15 (dd, IH), 3.79 (ddd, IH), 3.58-3.51 (m, 2H), 3.39-2.97 (m, 2H), 1.38 (d, 9H).
  • 2
  • [ 783350-37-8 ]
  • [ 106825-79-0 ]
YieldReaction ConditionsOperation in experiment
With trifluoroacetic acid; In dichloromethane; at 20℃; for 0.5h; (S)-4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acid (4.60 g, 20.0 mmol)Add to dichloromethane (20 mL),Add trifluoroacetic acid (20 mL) and stir at room temperature.After 30 minutes, the reaction is completed.The reaction mixture was dried to give the title compound.
 

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