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Chemical Structure| 100243-39-8 Chemical Structure| 100243-39-8

Structure of (S)-3-Pyrrolidinol
CAS No.: 100243-39-8

Chemical Structure| 100243-39-8

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Product Details of [ 100243-39-8 ]

CAS No. :100243-39-8
Formula : C4H9NO
M.W : 87.12
SMILES Code : O[C@@H]1CNCC1
MDL No. :MFCD00192426
InChI Key :JHHZLHWJQPUNKB-BYPYZUCNSA-N
Pubchem ID :2733874

Safety of [ 100243-39-8 ]

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

Computational Chemistry of [ 100243-39-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
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.

1.2
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

0.52
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.12

Water Solubility

Log S (ESOL):?

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

0.05
Solubility 98.8 mg/ml ; 1.13 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

-0.13
Solubility 64.4 mg/ml ; 0.74 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)

1.25

Application In Synthesis of [ 100243-39-8 ]

* 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 [ 100243-39-8 ]

[ 100243-39-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 501-53-1 ]
  • [ 100243-39-8 ]
  • [ 100858-32-0 ]
YieldReaction ConditionsOperation in experiment
92% With triethylamine; In dichloromethane; at 5 - 20℃; for 48h; Step 1: preparation of benzyl (3S)-3-hydroxypyrrolidine-1-carboxylate. A solution of (3S)-pyrrolidin-3-ol (10.0 g, 0.12 mol) in dichloromethane (130 mL) was cooled to 5C. Triethylamine (16.9 mL, 0.12 mol) was added, followed by drop wise addition ofbenzyl chloroformate (13.9 mL, 0.10 mol), ensuring that the temperature did not exceed5C. The reaction mixture was then allowed to stir at ambient temperature for 48h, after which it was poured into aqueous saturated sodium bicarbonate and extracted into dichloromethane. The combined organic layers were washed with aqueous saturated sodium bicarbonate, dried over magnesium sulfate, and concentrated in vacuo. The resulting crude oil was purified by silica gel column chromatography (50% ether hexanes followed by ether) to afford the title compound as a clear oil (14 g, 92%).
  • 2
  • [ 34368-52-0 ]
  • [ 100243-39-8 ]
YieldReaction ConditionsOperation in experiment
(S)-3-Hydroxy-2-pyrrolidineon 9 (0.1 mol, 10.11 g), diglym (1.13 mol, 151.65 g) and NaBH (0.4 mol, 15.13 g) were added to a 500D round-bottom flask at 25oC°C, and sulfuric acid (20.2 g) was gently dropped thereto for 1 hour. After the dropping, the mixture was heated to 8O0C and kept for 12 hours to complete the reaction. When the reaction was completed, methanol was added thereto to inactivate the reaction, and the reaction mixture was neutralized with diluted hydrochloric acid (0.4 mol, 41.67 g). Then, pH of the reaction mixture was adjusted to 11 or more by using an aqueous sol ution of sodium hydroxide (ION 35D), and salts precipitated therefrom were removed through filtration. A resulting filtrate was concentrated under reduced pressure to obtain a (S)-3-hydroxypyrrolidine 1 residue. The residue was distilled under reduced pressure to obtain pure (S)-3-hydroxypyrrolidine 1.[122] 1H-NMR (CDCl ): delta 4.3-4.4 (m, IH), 3.05-3.15 (m, IH), 3.0 (bs, 2H), 2.75-2.9 (m,3H), 1.85-2.0 (m, IH), 1.6-1.75 (m, IH). EPO <DP n="15"/>[123] [124]
EXAMPLE 9 Preparation of (S)-3-hydroxypyrrolidine 1 (S)-3-Hydroxy-2-pyrrolidineon 9 (0.1 mol, 10.11 g), diglym (1.13 mol, 151.65 g) and NaBH (0.4 mol, 15.13 g) were added to a 500.box. round-bottom flask at 25oC° C., and sulfuric acid (20.2 g) was gently dropped thereto for 1 hour. After the dropping, the mixture was heated to 80° C. and kept for 12 hours to complete the reaction. When the reaction was completed, methanol was added thereto to inactivate the reaction, and the reaction mixture was neutralized with diluted hydrochloric acid (0.4 mol, 41.67 g). Then, pH of the reaction mixture was adjusted to 11 or more by using an aqueous solution of sodium hydroxide (10N 35.box.), and salts precipitated therefrom were removed through filtration. A resulting filtrate was concentrated under reduced pressure to obtain a (S)-3-hydroxypyrrolidine 1 residue. The residue was distilled under reduced pressure to obtain pure (S)-3-hydroxypyrrolidine 1. 1H-NMR (CDCl3): delta 4.3-4.4 (m, 1H), 3.05-3.15 (m, 1H), 3.0 (bs, 2H), 2.75-2.9 (m, 3H), 1.85-2.0 (m, 1H), 1.6-1.75 (m, 1H).
  • 3
  • [ 85822-16-8 ]
  • [ 100243-39-8 ]
  • 4-(3-hydroxypyrrolidine-1-sulfonyl)-benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In methanol; at 20℃; for 1h; Step A: To <strong>[85822-16-8]4-formylbenzenesulfonyl chloride</strong> (1.0 g) in MeOH (10 mL) was added NaHCO3 (0.425 g, s), followed by S-(-)-3-hydroxypyrrolidine (0.533 g), and the mixture stirred at RT for 1 h. The product was filtered through celite, concentrated to provide an oil, and chromatographed on silica (3% MeOH/DCM) to provide 4-(3-hydroxypyrrolidine-1-sulfonyl)-benzaldehyde (1.14 g).
  • 4
  • [ 58656-98-7 ]
  • [ 100243-39-8 ]
  • [ 1057666-81-5 ]
YieldReaction ConditionsOperation in experiment
88% With potassium carbonate; In dimethyl sulfoxide; at 130℃; for 4h; Step 1: (S)-tert-Butyl 4-(3-hydroxypyrrolidin-1-yl)benzoate (157)To a solution of <strong>[58656-98-7]ter<strong>[58656-98-7]t-butyl 4-fluorobenzoate</strong></strong> (1 g, 5.1 mmol) and (S)-pyrrolidin-3-ol (462 mg, 5.3 mmol) in DMSO (10 mL) was added powdered potassium carbonate (705 mg, 5.1 mmol). The mixture was stirred at 130 C. for 4 h and allowed to cool down to room temperature. The mixture was diluted with EtOAc (300 mL) and the solution was washed with water (2×100 mL), dried over Na2SO4, filtered and concentrated to provide title compound 157 (1.23 g, 88% yield) that was used in the next step without further purification. LRMS (ESI): (calc) 263.15 (found) 264.1 (MH+).
  • 5
  • [ 182287-49-6 ]
  • [ 100243-39-8 ]
  • [ 1455472-20-4 ]
  • 6
  • [ 130723-13-6 ]
  • [ 144-55-8 ]
  • [ 100243-39-8 ]
  • (S)-1-(3-bromo-5-(trifluoromethyl)phenyl)pyrrolidin-3-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In dimethyl sulfoxide; A) (S)-1-(3-bromo-5-(trifluoromethyl)phenyl)pyrrolidin-3-ol A mixture of <strong>[130723-13-6]3-bromo-5-fluorobenzotrifluoride</strong> (1.07 g), (S)-3-pyrrolidinol (0.391 mL), cesium carbonate (1.72 g) and DMSO (10 mL) was irradiated with microwave at 120C for 30 min. The mixture was allowed to be cooled to room temperature, saturated aqueous sodium bicarbonate solution was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.05 g). MS (API+): 310.0 [M+H]+
  • 7
  • [ 446-18-4 ]
  • [ 100243-39-8 ]
  • (S)-1-(4-amino-5-methyl-2-nitrophenyl)pyrrolidin-3-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
72.3% With potassium carbonate; In tetrahydrofuran; at 70℃; for 12h; Step-2: Preparation of (S)-1-(4-amino-5-methyl-2-nitrophenyl)pyrrolidin-3-ol. A solution of <strong>[446-18-4]4-fluoro-2-methyl-5-nitroaniline</strong> (1 1g, 64.32mmol), potassium carbonate (35.5g, 257.30 mmol) and (S)-pyrrolidin-3-ol (8.7g, 70.76mmol) in THF was stirred at 70C for 12h. The reaction mixture was filtered and filtrate was purified by column chromatography elution with 50% ethyl acetate in hexane to obtain the title compound (11g, 72.3 %.). LCMS: 97.15% m/z = 238.3(M+1).
 

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