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Chemical Structure| 121103-15-9

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Product Details of [ 121103-15-9 ]

CAS No. :121103-15-9
Formula : C8H18N2O2
M.W : 174.24
SMILES Code : O=C(OC(C)(C)C)NC[C@@H](N)C
MDL No. :MFCD11112235
InChI Key :UYNSYFDLTSSUNI-LURJTMIESA-N
Pubchem ID :45072492

Safety of [ 121103-15-9 ]

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

Computational Chemistry of [ 121103-15-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 0
Fraction Csp3 0.88
Num. rotatable bonds 5
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 47.79
TPSA ?

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

64.35 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.19
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

0.42
Log Po/w (WLOGP)?

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

0.86
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.

0.63
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

-0.03
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.81

Water Solubility

Log S (ESOL):?

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

-0.85
Solubility 24.3 mg/ml ; 0.14 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.

-1.34
Solubility 7.99 mg/ml ; 0.0459 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

-1.31
Solubility 8.55 mg/ml ; 0.0491 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.

-7.06 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

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)

2.54

Application In Synthesis of [ 121103-15-9 ]

* 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.

  • Upstream synthesis route of [ 121103-15-9 ]

[ 121103-15-9 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 24424-99-5 ]
  • [ 19777-66-3 ]
  • [ 121103-15-9 ]
YieldReaction ConditionsOperation in experiment
42% With sodium hydroxide In methanol; water at 20℃; for 20 h; Inert atmosphere; Cooling with ice To a solution of (S)-1,2-diaminopropane dihydrochloride (16 g, 109 mmol) in MeOH (64 mL) and water (16 mL) was added di-tert-butyl dicarbonate (28.5 g, 131 mmol) in MeOH (16 mL).
The resulting solution was cooled in an ice bath, and 4N NaOH (35 mL, 140 mL) was added dropwise over 2 h.
The mixture was allowed to warm to rt and stirred for a total of 20 h.
The reaction was filtered, and the filtrate concentrated to remove MeOH. 200 mL EtOAc, 200 mL water, and 16 mL 1M HCl were added sequentially.
The layers were separated and the aqueous layer washed with EtOAc (200 mL).
The combined organic extracts were washed with 0.04M HCl (208 mL).
The organic phase was separated and discarded.
The aqueous phases were combined, adjusted to pH=14 with 10N NaOH (20 mL), and extracted with DCM (400 mL*2).
The combined organic extracts were dried (Na2SO4), filtered, and concentrated to afford the desired product as a clear oil (8.0 g, 42percent). MS (ESI): mass calcd. for C8H18N2O2, 174.1; m/z found, 175.2 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 5.01 (br s, 1H), 3.24-3.09 (m, 1H), 3.09-2.95 (m, 1H), 2.92-2.84 (m, 1H), 1.45 (s, 9H), 1.35-1.19 (m, 2H), 1.07 (d, J=6.4 Hz, 3H).
References: [1] Patent: US2014/275096, 2014, A1, . Location in patent: Paragraph 0126; 0147.
[2] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 2, p. 257 - 261.
[3] European Journal of Pharmacology, 2015, vol. 765, p. 551 - 559.
  • 2
  • [ 15967-72-3 ]
  • [ 121103-15-9 ]
  • [ 146552-71-8 ]
YieldReaction ConditionsOperation in experiment
36%
Stage #1: With triethylamine In ethanolHeating / reflux
Stage #2: With hydrogenchloride In water
Stage #3: With sodium hydroxide In water
A) (S)-2-Amino-propyl)-carbamic acid tert-butyl ester: To a solution of trietylamine (0.95 mL, 6.8 mmol) in 15 mL ethanol was added (s)-(-)- diaminopropane (252 mg, 74.1 mmol). The reaction mixture was stirred under reflux over night. Solvent was evaporated. Water was added and the pH was adjusted to pH 3 by addition of 2 M hydrochloric acid followed by extraction with dichloromethane. The aqueous phase was made alkaline by addition of 2 M sodium hydroxide and extracted with Q dichloromethane. The organic phase was dried over magnesium sulfate and dried in vacuo over night to give the sub-title compound (211 mg, 36 percent yield) and the by-product ((S)-2- amino-l-methyl-ethyl)-carbamic acid tert-butyl ester in a 3 : 1 mixture according to NMR.1H NMR (400 MHz; chloroform-d as solvent and internal reference) δ(ppm) 1.09 (d, 3H, / 5 = 6.5 Hz), 1.45 (s, 9H), 2.91 (m, IH), 3.04 (m, IH), 3.16 (m, IH)
36%
Stage #1: With triethylamine In ethanolHeating / reflux
Stage #2: With hydrogenchloride In water
A) ((S)-2-Amino-propyl)-carbamic acid tert-butyl ester: To a solution of trietylamine (0.95 mL, 6.8 mmol) in 15 mL ethanol was added (s)-(-)- diaminopropane (252 mg, 74.1 mmol). The reaction mixture was stirred under reflux over night. Solvent was evaporated. Water was added and the pH was adjusted to pH 3 by addition of 2 M hydrochloric acid followed by extraction with dichloromethane. The aqueous phase was made alkaline by addition of 2 M sodium hydroxide and extracted with dichloromethane. The organic phase was dried over magnesium sulfate and dried in vacuo over night to give the the sub-title compound (211 mg, 36 percent yield) and the by-product ((S)-2-amino-l-methyl-ethyl)-carbarnic acid tert-butyl ester in a 3 : 1 mixture according to NMR.1H NMR (400 MHz; chloroform-d as solvent and internal reference) δ(ppm) 1.09 (d, 3H, J = 6.5 Hz), 1.45 (s, 9H), 2.91 (m, IH), 3.04 (m, IH), 3.16 (m, IH)
References: [1] Patent: WO2007/8145, 2007, A1, . Location in patent: Page/Page column 27.
[2] Patent: WO2007/8144, 2007, A1, . Location in patent: Page/Page column 17; 23-24.
  • 3
  • [ 34619-03-9 ]
  • [ 19777-66-3 ]
  • [ 121103-15-9 ]
References: [1] Patent: WO2007/106852, 2007, A2, . Location in patent: Page/Page column 102.
  • 4
  • [ 15967-72-3 ]
  • [ 24424-99-5 ]
  • [ 121103-15-9 ]
References: [1] Patent: WO2006/74003, 2006, A2, . Location in patent: Page/Page column 139.
  • 5
  • [ 400652-51-9 ]
  • [ 121103-15-9 ]
References: [1] Journal of Combinatorial Chemistry, 2010, vol. 12, # 2, p. 248 - 254.
  • 6
  • [ 1299490-85-9 ]
  • [ 121103-15-9 ]
References: [1] Journal of the American Chemical Society, 2011, vol. 133, # 19, p. 7312 - 7315.
  • 7
  • [ 1299491-18-1 ]
  • [ 121103-15-9 ]
References: [1] Journal of the American Chemical Society, 2011, vol. 133, # 19, p. 7312 - 7315.
[2] Journal of the American Chemical Society, 2011, vol. 133, # 19, p. 7312 - 7315.
  • 8
  • [ 24424-99-5 ]
  • [ 121103-15-9 ]
References: [1] Journal of the American Chemical Society, 2011, vol. 133, # 19, p. 7312 - 7315.
[2] Journal of the American Chemical Society, 2011, vol. 133, # 19, p. 7312 - 7315.
 

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