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Structure of 177947-96-5

Chemical Structure| 177947-96-5

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Product Details of [ 177947-96-5 ]

CAS No. :177947-96-5
Formula : C9H15NO3
M.W : 185.22
SMILES Code : O=C(N1CC(C=O)C1)OC(C)(C)C
MDL No. :MFCD06656142
InChI Key :JVQOZRRUGOADSU-UHFFFAOYSA-N
Pubchem ID :10726182

Safety of [ 177947-96-5 ]

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

Computational Chemistry of [ 177947-96-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.78
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 51.99
TPSA ?

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

46.61 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.03
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

0.35
Log Po/w (WLOGP)?

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

0.67
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.

0.45
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

0.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.83

Water Solubility

Log S (ESOL):?

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

-0.94
Solubility 21.0 mg/ml ; 0.114 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.

-0.89
Solubility 23.7 mg/ml ; 0.128 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

-0.67
Solubility 40.1 mg/ml ; 0.216 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.

-7.18 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)

1.98

Application In Synthesis of [ 177947-96-5 ]

* 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 [ 177947-96-5 ]

[ 177947-96-5 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 177947-96-5 ]
  • [ 24134-09-6 ]
  • tert-butyl 3-((1,2-dimethyl-1H-imidazol-5-yl)(hydroxy)methyl)azetidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
A solution of n-BuLi (2.0 mL, 5 mmol, 2.5 M solution in hexane) was slowly added to a solution of <strong>[24134-09-6]5-bromo-1,2-dimethyl-1H-imidazole</strong> (0.88 g, 5.1 mmol) in THF (35 mL) at -78 C. After addition, stirring was continued for an additional 30 minutes and tert-butyl 3-formylazetidine-1-carboxylate (0.94 g, 5.1 mmol) dissolved in THF (12 mL) was slowly added. An additional 4 mL of THF was used to complete the quantitative addition. The mixture was stirred at -78 C. for 5 minutes then warmed to room temperature and stirred for 1 hour. The solution was quenched with aqueous saturated NH4Cl solution and layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The crude product was purified by triturating with DCM to provide the title compound.
  • 2
  • [ 177947-96-5 ]
  • [ 24134-09-6 ]
  • tert-butyl 3-(1,2-dimethyl-1H-imidazole-5-carbonyl)azetidine-1-carboxylate [ No CAS ]
  • 3
  • [ 177947-96-5 ]
  • [ 1986-47-6 ]
  • tert-butyl 3-[(trans-2-phenylcyclopropyl)amino]methyl}azetidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% Step 1: tert-butyl 3-[(trans-2-phenylcyclopropyl)amino]methyl}azetidine-1-carboxylate To a solution of tert-butyl 3-formylazetidine-1-carboxylate (556 mg, 3.00 mmol, Alfa Aesar: CatNo. H52794) and 2-phenylcyclopropanamine hydrochloride (600. mg, 3.54 mmol, trans, racemic, J&W PharmLab: CatNo.20-0073S, Lot: JW152-128A) in DCM (10 mL) was added acetic acid (510 muL, 9.0 mmol). The resulting yellow solution was stirred at room temperature overnight then Na(OAc)3BH (1.9 g, 9.0 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then diluted with DCM, washed with saturated Na2CO3, water and brine. The organic layer was dried over Na2SO4 then concentrated. The residue was purified on silica gel column eluting with 0 to 100% EtOAc/Hexanes to give the desired product (513 mg, 57%) as a light yellow oil. LC-MS calculated for C14Hi9N2O2 (M-tBu+2H)+: m/z=247.1; found 247.2.
57% Step 1: tert-butyl 3-[(trans-2-phenylcyclopropyl)amino]methyl}azetidine-1-carboxylate To the solution of tert-butyl 3-formylazetidine-1-carboxylate (556 mg, 3.00 mmol, Alfa Aesar: Cat No.H52794) and 2-phenylcyclopropanamine hydrochloride (600. mg, 3.54 mmol, trans, racemic, J&W PharmLab: Cat No.20-0073S, Lot: JW152-128A) in DCM (10 mL) was added acetic acid (510 muL, 9.0 mmol). The resulting yellow solution was stirred at room temperature overnight then Na(OAc)3BH (1.9 g, 9.0 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then diluted with DCM, washed with saturated Na2CO3, water and brine. The organic layer was dried over Na2SO4 then concentrated. The residue was purified on silica gel column eluting with 0 to 100% EtOAc/Hexanes to give the desired product (513 mg, 57%) as a light yellow oil. LC-MS calculated for C14H19N2O2 (M-tBu+2H)+: m/z=247.1; found 247.2.
  • 4
  • [ 610791-05-4 ]
  • [ 177947-96-5 ]
YieldReaction ConditionsOperation in experiment
61% With diisobutylaluminium hydride; In dichloromethane; at -78 - 0℃; for 0.5h;Inert atmosphere; Compound 41 (1.00 g, 5.30 mmol)Soluble in dichloromethane,Add to the three-necked bottle under Ar protection,After cooling to -78 C,DIBAL-H (11.7 mL, 11.7 mmol) was slowly added dropwise, and the addition was completed.After stirring at the same temperature for 30 min, slowly rise to 0 C.Stop the reaction by adding 2 mL of anhydrous methanol.200 mL of 10% aqueous citric acid solution was added. At this point, a white solid precipitated.Keep the temperature until the white solid disappears. Extracted 3 times with dichloromethane, dried, and concentrated the crude product by column chromatography (PE: EA=5:1)A colorless slightly viscous liquid compound 42 (0.57 g, 3.24 mmol),The yield was 61%.
  • 5
  • [ 177947-96-5 ]
  • [ 38573-88-5 ]
  • tert-butyl-3-[2,3-difluorophenyl(hydroxy)methyl]azetidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
6.55 g To a solution of <strong>[38573-88-5]2,3-difluorobromobenzene</strong> (10.0 g, 51.8 mmol) in dry diethyl ether (120 ml), under nitrogen at -78°C, was added drop wise , n-hexyllithium (2.3 M in hexane, 22.5 ml, 51 .8 mmol). The mixture was stirred for 10 mm after which a solution of tert-butyl 3-formylazetidine-i- carboxylate (12.2 g, 49.2 mmol) in dry diethyl ether (30 ml) was added drop wise. The resultingmixture was stirred at -78°C for 0.5 h and then brought to ambient temperature and stirred for 1 h. Water (50 ml) was added and the mixture was extracted with ethyl acetate (2x50 ml). The combined organic phase was washed with brine, dried (Mg504), filtered and evaporated to dryness. The crude product was purified by flash column chromatography on silica gel (ethyl acetate/isooctane, 0:1 to i:i)to give the title compound (6.55 g). MS mlz (rel. intensity, 70 eV)299 (M+, 2), 244 (36), 225 (29), 153(99), 57 (bp).
  • 6
  • [ 177947-96-5 ]
  • [ 1569-16-0 ]
  • [ 76-05-1 ]
  • (E)-tert-butyl3-(2-(1,8-naphthyridin-2-yl)vinyl)azetidine-1-carboxylate trifluoroacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% The mixture of 2-methyl-l,8-naphthyridine (115 mg, 0.799 mmol), E6A (148 mg, 0.799 mmol), and 4-methylbenzenesulfonamide (137 mg, 0.799 mmol) in DME (10 mL) was heated at 170 °C under microwave conditions for 2 h. The mixture was purified by preparative HPLC (Phenomenex Luna Axia 5mu Omicron18 30 chi 100 mm; 10 min gradient from 85percent A: 15percent B to 0percent A: 100percent B (A = 90percent H2O/10 percent ACN + 0.1percent TFA); (B = 90percent ACN/10percent H2O + 0.1percent TFA); detection at 220 nm) to yield E6B (170 mg, 68percent yield). LCMS (ES): m/z 312.2 [M+H]+.
 

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