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Chemical Structure| 167216-17-3 Chemical Structure| 167216-17-3

Structure of 167216-17-3

Chemical Structure| 167216-17-3

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Product Details of [ 167216-17-3 ]

CAS No. :167216-17-3
Formula : C9H19NO3
M.W : 189.25
SMILES Code : C[C@@H](NC(OC(C)(C)C)=O)CCO
MDL No. :MFCD18831346
InChI Key :JSZOAOLSEKSNTD-SSDOTTSWSA-N
Pubchem ID :29928104

Safety of [ 167216-17-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501

Computational Chemistry of [ 167216-17-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.89
Num. rotatable bonds 6
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 51.05
TPSA ?

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

58.56 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.18
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

1.03
Log Po/w (WLOGP)?

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

1.28
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.

0.95
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

0.62
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.21

Water Solubility

Log S (ESOL):?

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

-1.27
Solubility 10.3 mg/ml ; 0.0542 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.

-1.85
Solubility 2.67 mg/ml ; 0.0141 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

-1.5
Solubility 5.93 mg/ml ; 0.0313 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

Yes
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.

-6.72 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)

2.57

Application In Synthesis of [ 167216-17-3 ]

* 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 [ 167216-17-3 ]

[ 167216-17-3 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 159877-47-1 ]
  • [ 167216-17-3 ]
YieldReaction ConditionsOperation in experiment
1.3 g
Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran at -78℃; for 1 h; Inert atmosphere
Stage #2: With sodium hydroxide In water at 20℃; for 1 h;
To a solution of (R)-3-((tert-butoxycarbonyl)amino)butanoate (3.0 g, 14.76 mmol) in tetrahydrofuran (THF) (50 mL) was added aluminum(III) lithium hydride (0.728 g, 19.19 mmol), stirred at -78 °C for 1 h under nitrogen. The reaction mixture was warmed to 0°C, quenched by addition of H20 (0.7 mL) and aq. 15percent NaOH (0.7 mL), stirred for 1 h at r.t, filtered through celite, dried over Na2S04, concentrated to afford the title compound (1.3 g).
References: [1] Advanced Synthesis and Catalysis, 2010, vol. 352, # 1, p. 92 - 96.
[2] Patent: US2011/237814, 2011, A1, . Location in patent: Page/Page column 11.
[3] Patent: WO2014/114249, 2014, A1, . Location in patent: Page/Page column 21.
  • 2
  • [ 159991-23-8 ]
  • [ 167216-17-3 ]
YieldReaction ConditionsOperation in experiment
95% With sodium tetrahydroborate; boron trifluoride diethyl etherate In tetrahydrofuran at -20℃; Green chemistry 100 g of N-Boc-(R)-3-aminobutyric acid and 300 mL of tetrahydrofuran were placed in a reaction flask, 20.6 g of sodium borohydride was added in portions, the temperature was lowered to -20 °C, and 100 g of boron trifluoride etherate was slowly added dropwise. HPLC to determine whether the raw material reaction is complete. After completion of the reaction, the reaction was quenched by the addition of methanol, and the solvent was evaporated. Filter to remove solids,The filtrate was washed with 100 ml of saturated sodium bicarbonate.The organic phase was concentrated to give N-Boc-(R)-3-aminobutanol as a white solid, 88 g, yield 95percent, mp. 99.0percent (HPLC method).
91% With sodium tetrahydroborate; iodine In tetrahydrofuran at 0 - 30℃; 115 g of the compound of formula I was dissolved in 460 mL of tetrahydrofuran, cooled to 0~10 ° C. in an ice bath, 23.7 g of sodium borohydride was added in portions, the temperature was controlled at 0~10 ° C., and 165.4 g of elemental iodine Of 230 mL of tetrahydrofuran solution, the dropwise addition, and gradually warmed to 25 ~ 30 ° C,Liquid phase tracking is complete until the conversion of the raw material, 60 mL of water is added dropwise to quench the reaction, concentrated under reduced pressure to no distillate, 500 mL of methanol is added, the temperature is raised to 55-60 ° C., the solution is incubated for 0.5 h, mL water, drops After completion of the incubation, the mixture was stirred for 1 hour, then slowly cooled to 15-20 ° C, filtered and dried to obtain 97.4 g of the compound of formula II in a yield of 91percent.
References: [1] Patent: CN108424370, 2018, A, . Location in patent: Paragraph 0090; 0091.
[2] Patent: CN106966912, 2017, A, . Location in patent: Paragraph 0022; 0023; 0024.
  • 3
  • [ 24424-99-5 ]
  • [ 61477-40-5 ]
  • [ 167216-17-3 ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine In dichloromethane at 20 - 24℃; for 4 h; Example 36
Preparation of (R)-tert-butyl(4-hydroxybutan-2-yl)carbamate (C56)
Triethylamine (2.35 mL, 16.8 mmol) and di-tert-butyl dicarbonate (2.50 g, 12.3 mmol) were added to a solution of (R)-3-aminobutan-1-ol (1.00 g, 11.2 mmol) in dichloromethane (10 mL).
The reaction mixture was stirred for 4 hours at room temperature.
The reaction mixture was concentrated, the residue poured into ice water, and then extracted with ethyl acetate.
The organic layer was washed with water, dried over sodium sulfate, filtered, and concentrated.
Purification by flash column chromatography using 20percent ethyl acetate/petroleum ether as eluent provided the title compound as a white solid (1.7 g, 80percent): 1H NMR (400 MHz, DMSO-d6) δ 6.62 (d, J=8.4 Hz, 1H), 4.43-4.31 (m, 1H), 3.55-3.52 (m, 1H), 3.40-3.38 (m, 2H), 1.55-1.48 (m, 2H), 1.43 (s, 9H), 1.01 (d, J=6.8 Hz, 3H).
References: [1] Patent: US2017/210723, 2017, A1, . Location in patent: Paragraph 0537-0538.
  • 4
  • [ 161529-22-2 ]
  • [ 167216-17-3 ]
References: [1] Patent: WO2005/26113, 2005, A1, . Location in patent: Page 32-33.
  • 5
  • [ 1047665-48-4 ]
  • [ 167216-17-3 ]
References: [1] Chemistry - A European Journal, 2009, vol. 15, # 9, p. 2050 - 2054.
[2] Chemistry - A European Journal, 2009, vol. 15, # 40, p. 10514 - 10532.
  • 6
  • [ 24424-99-5 ]
  • [ 167216-17-3 ]
References: [1] Patent: WO2014/114249, 2014, A1, .
 

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