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Chemical Structure| 104587-62-4 Chemical Structure| 104587-62-4

Structure of (S)-Azetidine-2-methanol
CAS No.: 104587-62-4

Chemical Structure| 104587-62-4

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Product Details of [ 104587-62-4 ]

CAS No. :104587-62-4
Formula : C4H9NO
M.W : 87.12
SMILES Code : OC[C@H]1NCC1
MDL No. :MFCD10565790
InChI Key :FTWWNKCHSPDIQW-BYPYZUCNSA-N
Pubchem ID :10855374

Safety of [ 104587-62-4 ]

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

Computational Chemistry of [ 104587-62-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 27.11
TPSA ?

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

32.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.11
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

-0.69
Log Po/w (WLOGP)?

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

-1.04
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.

-0.57
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

0.45
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.15

Water Solubility

Log S (ESOL):?

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

0.12
Solubility 115.0 mg/ml ; 1.32 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.

0.49
Solubility 268.0 mg/ml ; 3.07 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

-0.26
Solubility 48.2 mg/ml ; 0.553 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

Low
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.

-7.32 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)

1.16

Application In Synthesis of [ 104587-62-4 ]

* 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 [ 104587-62-4 ]

[ 104587-62-4 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 2133-34-8 ]
  • [ 104587-62-4 ]
YieldReaction ConditionsOperation in experiment
Borane tetrahydrofuran complex (1.0M solution in tetrahydrofuran,25.0 mL, 24.7 mmol) was added to a solution of L-azetidine-2-carboxtlicacid (5, 1.0 g, 9.9 mmol) in tetrahydrofuran (15.0 mL) under nitrogenatmospheric conditions. The resulting mixture was stirred for 90 minunder reflux. Afetr the reaction had cooled to room temperature, anaqueous solution of potassium hydrogen sulfate (10%, 15.0 mL) wasadded to the mixture, which was further refluxed for 15 min. Themixture was evaporated under reduced pressure to yield the residue of(S)-azetidine-2-ylmethanol. An aqueous solution of sodium hydroxide(1 M, 20.0 mL) and di-tert-butyl dicarbonate (2.4 g, 11.9 mmol) wereadded to a solution of (S)-azetidine-2-ylmethanol (862 mg, 9.9 mmol)in water (20.0 mL) and 1,4-dioxane (15.0 mL) at 0 C. The mixture wasthen stirred for 24 h at room temperature. The reaction mixture waspoured into a saturated aqueous solution of sodium bicarbonate andextracted with chloroform. The organic layer was dried over sodiumsulfate and concentrated under reduced pressure. The residue waspurified by silica gel column chromatography (n-hexane/ethylacetate=1/1) to yield (-)-6 (1.79 g, 97%) in the form of a colorless oil.
With borane-THF; In tetrahydrofuran; at 90℃; for 1.5h;Inert atmosphere; To a solution of <strong>[2133-34-8]L-azetidine-2-carboxylic acid</strong> (1.0 g, 9.9 mmol, >99% e.e.) in THF (15 mL), a borane-THF complex (1.0 M solution in THF, 25 mmoL) was added. The mixture was refluxed under a N2 stream for 1.5 hr. Potassium hydrogen sulfate (10% solution in water,15 mL) was added to the mixture, and then the mixture was refluxed for15 min. Solvent was removed under reduced pressure to afford a white solid. Water (20 mL), 1,4-dioxane (15 mL), sodium hydroxide (1M solution in water, 20 mL), and di-tert-butyl dicarbonate (2.4 g, 11.9 mmol) at 0 C were added to the residue. The mixture was stirred at 0 C for 30 min and then warmed to room temperature and stirred overnight. After the reaction, a saturated aqueous ammonium chloride solution was added to the mixture. Compounds were extracted with chloroform, and the organic layer was dried with sodium sulfate. The solvent was removed under reduced pressure. Purification by silica gel flash-chromatography (hexane / ethyl acetate=1 / 1) yielded 1 (1.79 g,9.6 mmol, 97%) as a colorless oil. 1H NMR (300 MHz, CDCl3) delta; 4.42(broad s, 1H), 3.91-3.73 (m, 4H), 2.32 (broad s, 1H), 2.24-2.13 (m,1H), 1.96 (broad s, 1H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3) delta;157.1, 80.1, 66.4, 63.5, 46.6, 28.2, 17.9. MS (FAB+) m/z; 188([M+H]+). HRMS (FAB+) m/z; 188.1282 (Calcd: 188.1287 forC9H18NO3+). [alpha]D20= -20.59 (c=1.19, CHCl3, determined on asample with 99.5% e.e.), lit.13 [alpha]D= -20.3 (c=0.72, CHCl3).
  • 2
  • [ 24424-99-5 ]
  • [ 677-22-5 ]
  • [ 155878-39-0 ]
  • [ 104587-62-4 ]
  • [ 161511-85-9 ]
YieldReaction ConditionsOperation in experiment
97.0% With sodium bicarbonate; sulfuric acid; magnesium chloride; In tetrahydrofuran; water; ethyl acetate; toluene; EXAMPLE 5 Synthesis of (S)-N-t-butoxycarbonylazetidine-2-methanol (Effect of Addition of t-butylmagnesium Chloride and Magnesium Chloride) STR12 In a nitrogen gas atmosphere, a reaction flask was charged with the isopropyl (2S)-4-oxo-2-azetidinecarboxylate obtained in Reference Example 2 (5.00 g, 31.8 mmol), magnesium chloride (4.54 g, 47.8 mmol) and THF (50 mL) and while maintaining the temperature of this solution at 5 to 15 C., t-butylmagnesium chloride (2 M solution in THF, 15.9 mL, 31.8 mmol) was added, followed by 1.5 hours of further stirring at that temperature. While maintaining the temperature of that solution at 5 to 15 C., a solution of lithium aluminum hydride (1.81 g, 47.8 mmol) in THF (10 mL) was added and, thereafter, the mixture was heated under reflux with stirring for 6 hours. The reaction mixture was then cooled to 5 C., water (100 mL) was added, and the mixture was further stirred at room temperature for 0.5 hour. This solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (3.37 g, 31.8 mmol) was then added, and di-t-butyl dicarbonate (7.63 g, 35.0 mmol) was added at room temperature. Thereafter, stirring was continued for 14 hours. The reaction mixture was adjusted to pH 7 and extracted with ethyl acetate (50 mL*2), and the extract was washed with water (50 mL*1), dried over magnesium sulfate and filtered. The filtrate was concentrated and subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase for separation/purification, to give an oil (5.77 g). Based on its proton NMR spectrum (FIG. 5), said oil was identified as the desired product (S)-N-t-butoxycarbonylazetidine-2-methanol (yield 97.0%).
  • 3
  • [ 24424-99-5 ]
  • [ 104587-62-4 ]
  • [ 161511-85-9 ]
YieldReaction ConditionsOperation in experiment
1.76 g With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃; for 24h; Borane tetrahydrofuran complex (1.0M solution in tetrahydrofuran,25.0 mL, 24.7 mmol) was added to a solution of L-azetidine-2-carboxtlicacid (5, 1.0 g, 9.9 mmol) in tetrahydrofuran (15.0 mL) under nitrogenatmospheric conditions. The resulting mixture was stirred for 90 minunder reflux. Afetr the reaction had cooled to room temperature, anaqueous solution of potassium hydrogen sulfate (10%, 15.0 mL) wasadded to the mixture, which was further refluxed for 15 min. Themixture was evaporated under reduced pressure to yield the residue of(S)-azetidine-2-ylmethanol. An aqueous solution of sodium hydroxide(1 M, 20.0 mL) and di-tert-butyl dicarbonate (2.4 g, 11.9 mmol) wereadded to a solution of (S)-azetidine-2-ylmethanol (862 mg, 9.9 mmol)in water (20.0 mL) and 1,4-dioxane (15.0 mL) at 0 C. The mixture wasthen stirred for 24 h at room temperature. The reaction mixture waspoured into a saturated aqueous solution of sodium bicarbonate andextracted with chloroform. The organic layer was dried over sodiumsulfate and concentrated under reduced pressure. The residue waspurified by silica gel column chromatography (n-hexane/ethylacetate=1/1) to yield (-)-6 (1.79 g, 97%) in the form of a colorless oil: 1H NMR (300 MHz, CDCl3) δ: 4.42 (br s, 1H), 3.91-3.73 (m, 4H),2.32 (br s, 1H), 2.24-2.13 (m, 1H), 1.96 (brs, 1H), 1.45 (s, 9H); 13CNMR (75 MHz, CDCl3) δ: 157.1, 80.1, 66.4, 63.5, 46.6, 28.2 (3), 17.87;IR (CHCl3) cm-1: 3400, 3005, 2978, 1666, 1414, 1369; FAB-MS m/z:188.1282 (Calcd for C9H18NO3: 188.1287); MS (FAB) m/z:188(M++H, 31); [α]D20=-20.59 (c=1.19, CHCl3).
1.79 g With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃;Inert atmosphere; To a solution of L-azetidine-2-carboxylic acid (1.0 g, 9.9 mmol, >99% e.e.) in THF (15 mL), a borane-THF complex (1.0 M solution in THF, 25 mmoL) was added. The mixture was refluxed under a N2 stream for 1.5 hr. Potassium hydrogen sulfate (10% solution in water,15 mL) was added to the mixture, and then the mixture was refluxed for15 min. Solvent was removed under reduced pressure to afford a white solid. Water (20 mL), 1,4-dioxane (15 mL), sodium hydroxide (1M solution in water, 20 mL), and di-tert-butyl dicarbonate (2.4 g, 11.9 mmol) at 0 C were added to the residue. The mixture was stirred at 0 C for 30 min and then warmed to room temperature and stirred overnight. After the reaction, a saturated aqueous ammonium chloride solution was added to the mixture. Compounds were extracted with chloroform, and the organic layer was dried with sodium sulfate. The solvent was removed under reduced pressure. Purification by silica gel flash-chromatography (hexane / ethyl acetate=1 / 1) yielded 1 (1.79 g,9.6 mmol, 97%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ; 4.42(broad s, 1H), 3.91-3.73 (m, 4H), 2.32 (broad s, 1H), 2.24-2.13 (m,1H), 1.96 (broad s, 1H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3) δ;157.1, 80.1, 66.4, 63.5, 46.6, 28.2, 17.9. MS (FAB+) m/z; 188([M+H]+). HRMS (FAB+) m/z; 188.1282 (Calcd: 188.1287 forC9H18NO3+). [α]D20= -20.59 (c=1.19, CHCl3, determined on asample with 99.5% e.e.), lit.13 [α]D= -20.3 (c=0.72, CHCl3).
 

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