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Chemical Structure| 2955-88-6 Chemical Structure| 2955-88-6

Structure of 2-(Pyrrolidin-1-yl)ethanol
CAS No.: 2955-88-6

Chemical Structure| 2955-88-6

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Product Details of [ 2955-88-6 ]

CAS No. :2955-88-6
Formula : C6H13NO
M.W : 115.17
SMILES Code : OCCN1CCCC1
MDL No. :MFCD00003181
InChI Key :XBRDBODLCHKXHI-UHFFFAOYSA-N
Pubchem ID :76288

Safety of [ 2955-88-6 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225
Precautionary Statements:P210-P403+P235
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 2955-88-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 36.81
TPSA ?

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

23.47 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.81
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

0.6
Log Po/w (WLOGP)?

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

-0.31
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.

0.21
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

0.79
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.62

Water Solubility

Log S (ESOL):?

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

-0.8
Solubility 18.3 mg/ml ; 0.158 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.

-0.67
Solubility 24.8 mg/ml ; 0.215 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

-0.5
Solubility 36.1 mg/ml ; 0.313 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.

-6.58 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)

1.0

Application In Synthesis of [ 2955-88-6 ]

* 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 [ 2955-88-6 ]

[ 2955-88-6 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 2955-88-6 ]
  • [ 112108-73-3 ]
  • [ 862874-06-4 ]
YieldReaction ConditionsOperation in experiment
87% With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 50℃; 5 mmol 2-Chloro-4-fluoro-5-nitrotoluene, 5-7.5 mmol substituted 2-amino ethanol (R (CH2) 20H) and 11.5-12. 5 mmol cesiumcarbonate are dissolved in DMF and stirred at room temperature or 50-80 C until a full conversion is achieved. Depending from from the reaction route chosen, the reaction mixture is worked up according the following variants: Variant A: the reaction mixture is filtered and the residue rinsed with ethyl acetate. The filtrate is diluted with ethyl acetate, washed 3x with water and 1 x with brine, dried over Na2SO4, filtered and evaporated. The residue is purified by column chromatography (silica gel, eluent : DCM/MeOH 0-5% in 45min). Variant B: the reaction mixture is filtered by suction and rinsed with little DMF. The filtrate is evaporated. The oily residue is taken up in 100 ml water and extracted 3x with acyl acetate. The combined organic phases are washed 2x with water and 1x with brine, dried over Na2SO4, and evaporated. The residue is purified by column chromatography (silica gel, eluent : DCM/MeOH 0-5% in 45min). Variant C: the reaction mixture is filtered by suction and rinsed with little DMF. The filtrate is evaporated. The oily residue is taken up in 100 ml water and extracted 3x with acyl acetate. The combined organic phases are washed 2x with water and 1x with brine, dried over Na2SO4, and evaporated. Substituents, reaction conditions and yields : 7c: R = (CH2) 2N (CH2) 4; 50 C, over night, working up procedure: C, 87 %, red-brown solid 7d: R = (CH2) 2N (CH3) 2 ; 50 C, overnight, working up procedure: C, 93 %, brown oil 7e: R = (CH2) 2N (C2H5) 2; 50 C, overnight, working up procedure: B, 72 %, yellow oil 7f: R = (CH2) 2N (CH2) 20 (CH2) 2 ; 50 C, overnight, working up procedure: B, 71 %, brown crystals 7g: R = (CH2) 2N (CH2) 2NBoc (CH2) 2; 50 OC, overnight, working up procedure: C, 90 %, brown oil
  • 2
  • [ 2955-88-6 ]
  • [ 454-16-0 ]
  • [ 2287-10-7 ]
YieldReaction ConditionsOperation in experiment
54.19% With caesium carbonate; In N,N-dimethyl-formamide; at 90℃; for 2h; To a stirred solution of <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (ig, 5.84mmole) in DMF (lOmI) was added Cs2CO3 (2.85g, 8.76mmole) and 2-(pyrrolidin-1 -yl)ethan-1 -ol (807mg, 7.01 2mmole). The reaction mixture was stirred for 2hrs at 90°C. Water (25m1) was added and the crude product was extracted with ethyl acetate (25m1 x 3). Combined organic layers were washed with brine (25m1 x 3), dried over sodium sulfate and evaporated under vacuum to get crude material. The obtained crude was purified by flash chromatography to get pure title compound (840mg, Yield:54.19percent).LCMS: 99.65percent ESI-MS (m/z): 266.97 [M+1].
  • 3
  • [ 2955-88-6 ]
  • [ 574745-97-4 ]
  • 4-chloro-7-methoxy-6-[(2-pyrrolidin-1-yl)ethylhydroxy]quinazoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% The 6.5g of (compound 2), 4.6gN-(2-hydroxy-ethyl) pyrrolidine, 10.54gPPh3dissolved in 120 ml thf, placed in 250 ml of the protection of nitrogen in the three-necked round-bottom flask, hours under ice bath 3 batch, interval 3 hours/time, adding 9.25gDTAD, stirring the mixture at room temperature for 12 hours. By adding 100 ml water to terminate the reaction, the reaction solution with 200 ml dichloromethane extraction 3 time, combined with the organic layer, washing with saturated sodium chloride aqueous solution 1 time. Separating the organic layer in the 250 ml triangular flask adding anhydrous sodium sulfate for drying 6 hours, vacuum filtration. Filtrate concentrated to dry, purify by column chromatography by 4g (yield 42%) of compound 3, it is a colorless powder.
42% The 6.5g4- chloro-7-methoxy-quinazolin-6-ol (Compound 2), 4.6gN- (2- hydroxyethyl) pyrrolidine, 10.54gPPh3 was dissolved in 120mL of tetrahydrofuran, placed in a 250mL three nitrogen neck round bottom flask, under ice in 3 batches, 3 hour intervals / times, adding 9.25gDTAD, stirred at room temperature for 12 hours. 100 mL of water was added to terminate the reaction, the reaction solution was extracted 3 times with 200mL methylene chloride, the organic layers combined, washed once with saturated aqueous sodium chloride solution. The separated organic layer was dried over anhydrous sodium sulfate was added 6 hours in 250mL flask, filtered under reduced pressure. The filtrate was concentrated under reduced pressure to dryness, purified by column chromatography to give 4g (42% yield) of compound 3 as a colorless powder.
42% The 6.5g4- chloro-7-methoxy-quinazolin-6-ol (Compound 2), 4.6gN- (2- hydroxyethyl) pyrrolidine,10.54gPPh3 was dissolved in 120mL of tetrahydrofuran, placed in a nitrogen 250mL three-necked round-bottomed flask,Under ice in 3 batches, 3 hour intervals / times, adding 9.25gDTAD, stirred at room temperature for 12 hours. Join 100mL of water to terminate the reaction, the reaction solution was extracted 3 times with 200mL methylene chloride, the combined organic layers with saturated sodium chlorideAqueous solution of 1 times. The separated organic layer was dried over anhydrous sodium sulfate was added 6 hours in 250mL flasks, SavePressure filtration. The filtrate was concentrated under reduced pressure to dryness, purified by column chromatography to give 4g (42% yield) of compound 3 as a colorless powderend
42% The 6.5g4- chloro-7-methoxy-quinazolin-6-ol (Compound 2), 4.6gN- (2- hydroxyethyl) pyrrolidine, 10.54gPPh3It was dissolved in 120mL of tetrahydrofuran, placed in a nitrogen 250mL three-necked round bottom flask, under ice-three batches, 3 hour intervals / times, adding 9.25gDTAD, stirred for 12 hours at room temperature.100mL of water was added to terminate the reaction, the reaction solution was extracted 3 times with 200mL methylene chloride, the organic layers combined, washed with saturated aqueous sodium chloride solution once.The separated organic layer was dried over anhydrous sodium sulfate was added 6 hours in 250mL flask, filtered under reduced pressure.The filtrate was concentrated under reduced pressure to dryness, purified by column chromatography to give (42% yield) compound 4g 3, as a colorless powder
42% With triphenylphosphine; In tetrahydrofuran; for 15h;Cooling with ice; Inert atmosphere; Chloro-7-methoxyquinazolin-6-ol (Compound 2), 4.6 g of N- (2-hydroxyethyl) pyrrolidine, 10.54 g of PPh3 were dissolved in 120 mL of tetrahydrofuran,Was placed in a 250 mL nitrogen-protected, three-necked round bottom flask in 3 batches in an ice bath at intervals of 3 h. Add 9.25 g of DTAD and stir for 12 hours at room temperature. The reaction was terminated by the addition of 100 mL of water,The reaction solution was extracted three times with 200 mL of methylene chloride, and the combined organic layer was washed once with a saturated aqueous sodium chloride solution. The organic layer was separated, dried over anhydrous sodium sulfate for 6 hours in a 250 mL Erlenmeyer flask,Filtered under reduced pressure. The filtrate was concentrated to dryness under reduced pressure, and 4 g (yield 42%) of compound 3 was obtained as a colorless powder by column chromatography.

 

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