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Structure of 127838-58-8

Chemical Structure| 127838-58-8

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Product Details of [ 127838-58-8 ]

CAS No. :127838-58-8
Formula : C6H7NO2
M.W : 125.13
SMILES Code : OCC1=CC(=O)NC=C1
MDL No. :MFCD12033137
InChI Key :NVWMXLBVGGYAQW-UHFFFAOYSA-N
Pubchem ID :11094610

Safety of [ 127838-58-8 ]

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

Computational Chemistry of [ 127838-58-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 33.19
TPSA ?

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

53.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.12
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

-1.13
Log Po/w (WLOGP)?

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

-0.28
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.

-0.29
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

1.36
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.

-0.33
Solubility 58.4 mg/ml ; 0.466 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.

0.51
Solubility 402.0 mg/ml ; 3.21 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

-1.72
Solubility 2.39 mg/ml ; 0.0191 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

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.

-7.87 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)

1.4

Application In Synthesis of [ 127838-58-8 ]

* 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 [ 127838-58-8 ]

[ 127838-58-8 ] Synthesis Path-Downstream   1~20

  • 1
  • [ 89937-77-9 ]
  • [ 127838-58-8 ]
YieldReaction ConditionsOperation in experiment
88% To a suspension of methyl 2-oxo-1 ,2-dihydro-4-pyridinecarboxylate (1.37 g, 8.98 mmol) in anhydrous tetrahydrofuran (23 ml_) was added dropwise 2 M lithium borohydride/tetrahydrofuran (22.5 ml_, 45 mmol), and the mixture was heated to 550C under a nitrogen atmosphere for 3.5 h. Methanol (15 ml_) and water (3 ml_) were carefully added, and the mixture was stirred at ambient temperature for 30 min. The mixture was concentrated and more methanol (10 ml_) was added carefully. After stirring for 30 min, the mixture was adsorbed on silica gel and placed on top of a silica gel column, eluting with 0 to 30% methanokdichloromethane, to obtain the title compound as an off-white solid (0.99 g, 88%): 1H NMR (400 MHz, DMSOd6) delta ppm 11.29 (br s, 1 H), 7.23 (d, J = 6.7 Hz, 1 H), 6.21 (s, 1 H), 6.03 (dd, J = 6.7, 1.3 Hz, 1 H), 5.27 (t, J = 5.9 Hz, 1 H), 4.28 (d, J = 5.9 Hz, 2H).
61.2% With diisobutylaluminium hydride; In tetrahydrofuran; at 20℃; for 3h; To a stirred solution of methyl 2-oxo- 1 ,2-dihydropyridine-4-carboxylate (300 mg, 1.96 mmol) in THF (20 mL) was added diisobutylaluminium hydride (1.0 M in THF, 20 mL, 20 mmol). The mixture was stirred at RT for 3h, then MeOH (2 mL) and H20 (1 mL) were added. The mixture was stirred at RT for 20 minutes and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (DCM : MeOH = 8 : 1) to afford 4-(hydroxymethyl)pyridin-2(lH)-one as a white solid (150 mg, 61.2%). MS (ES+) C6H7N02 requires: 125, found: 126 [M+H]+.
With lithium borohydride; In tetrahydrofuran; methanol; chloroform; water; N,N-dimethyl-formamide; Step 1 4-Hydroxymethyl-1H-pyridin-2-one 2-Oxo-1,2-dihydropyridine-4-carboxylic acid methyl ester (1.8 g, 12.2 mmol), prepared as described in J. Org. Chem., 26, 428 (1961), was suspended in THF (100 ml). A small amount of DMF was added to help increase solubility. LiBH4 (61 mmol) was added and the reaction was stirred for 18 hours at room temperature. MeOH and H2O are added to quench the reaction. The reaction is then concentrated to yield a yellow oil. Flash chromatography (5% MeOH/CHCl3 to 20% MeOH/CHCl3) yielded 4-hydroxymethyl-1H-pyridin-2-one as a white solid. 1H NMR (400 MHz, CD3OD) delta 7.38-7.36 (1H,d); 6.56 (s, 1H); 6.37-6.36 (d, 1H); 4.50 s, 2H).
  • 2
  • [ 127838-58-8 ]
  • [ 18162-48-6 ]
  • [ 127838-40-8 ]
YieldReaction ConditionsOperation in experiment
88% With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃; for 18h; To a suspension of 4-(hydroxymethyl)-2(1 /-/)-pyridinone (0.98 g, 7.9 mmol) and DMF (10 ml_) was added imidazole (0.64 g, 9.45 mmol) and ferf-butyldimethylsilyl chloride (1.25 g, 8.26 mmol), and the mixture was stirred at ambient temperature under a nitrogen atmosphere for 18 h. The mixture was poured into water (30 ml_), and stirred for 30 min. The solid was filtered, rinsed with water, and air-dried to provide 4-([(1 ,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2(1 /-/)-pyridinone as an off-white solid (1.64 g, 88%): 1H NMR (400 MHz, DMSOd6) delta ppm 1 1.34 (br s, 1 H), 7.26 (d, J = 6.6 Hz, 1 H), 6.21 (s, 1 H), 6.01 (dd, J = 6.6, 1.5 Hz, 1 H), 4.5 (s, 2H), 0.88 (s, 9H), 0.05 (s, 6H); EI-LCMS m/z 241 (M+H)+.
  • 4
  • [ 127838-58-8 ]
  • [ 127838-42-0 ]
  • 5
  • [ 127838-58-8 ]
  • [ 127838-41-9 ]
  • 8
  • [ 127838-58-8 ]
  • [ 127838-43-1 ]
  • 10
  • [ 127838-58-8 ]
  • [ 127838-45-3 ]
  • 11
  • [ 288-32-4 ]
  • [ 127838-58-8 ]
  • [ 18162-48-6 ]
  • 4-(tert-butyldimethylsilyloxymethyl)-1H-pyridin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; Step 2 4-(tert-butyldimethylsilyloxymethyl)-1H-pyridin-2-one 4-Hydroxymethyl-1H-pyridin-2-one from Step 1 (1.3 g, 10.5 mmol) was dissolved in DMF. t-Butyl dimethylsilyl chloride (12.6 mmol, 1.9 g) and imidazole (12.6 mmol, 858 mg) were added and the reaction was stirred for 16 hours. The reaction mixture was diluted with EtOAc and washed with H2O (2*) and brine. The organic layer was dried (MgSO4), filtered and concentrated to yield a yellow oil. Flash chromatography (EtOAC) yielded 4-(tert-butyldimethylsilyloxy-methyl)-1H-pyridin-2-one as an off white solid. 1H NMR (400 MHz, CDCl3) delta 7.30-7.28 (d, 1H); 6.60 (s, 1H); 6.20-6.18 (d, 1H); 4.58 (s, 2H); 0.955 (s, 9H); 0.11 (s, 6H).
In N,N-dimethyl-formamide; Step 2 4-(tert-butyldimethylsilyloxymethyl)-1H-pyridin-2-one 4-Hydroxymethyl-1H-pyridin-2-one from Step 1 (1.3 g, 10.5 mmol) was dissolved in DMF. t-Butyl dimethylsilyl chloride (12.6 mmol, 1.9 g) and imidazole (12.6 mmol, 858 mg) were added and the reaction was stirred for 16 hours. The reaction mixture was diluted with EtOAc and washed with H2 O (2x) and brine. The organic layer was dried (MgSO4), filtered and concentrated to yield a yellow oil Flash chromatography (EtOAC) yielded 4-(tert-butyldimethylsilyloxy-methyl)-1H-pyridin-2-one as an off white solid. 1 H NMR (400 MHz, CDCl3) delta 7.30-7.28 (d, 1H); 6.60 (s, 1H); 6.20-6.18 (d, 1H); 4.58 (s, 2H); 0.955 (s, 9H); 0.11 (s, 6H).
  • 12
  • [ 7732-18-5 ]
  • [ 89937-77-9 ]
  • [ 127838-58-8 ]
YieldReaction ConditionsOperation in experiment
With lithium borohydride; In tetrahydrofuran; methanol; chloroform; N,N-dimethyl-formamide; Step 1 4-Hydroxymethyl-1H-pyridin-2-one 2-Oxo-1,2-dihydropyridine-4-carboxylic acid methyl ester (1.8 g, 12.2 mmol), prepared as described in J. Org. Chem., 26, 428 (1961), was suspended in THF(100 ml). A small amount of DMF was added to help increase solubility. LiBH4 (61 mmol) was added and the reaction was stirred for 18 hours at room temperature. MeOH and H2 O are added to quench the reaction. The reaction is then concentrated to yield a yellow oil. Flash chromatography (5% MeOH/CHCl3 to 20% MeOH/CHCl3) yielded 4-hydroxymethyl-1H-pyridin-2-one as a white solid. 1 H NMR (400 MHz, CD3 OD) delta 7.38-7.36 (1H,d); 6.56 (s, 1H); 6.37-6.36 (d, 1H); 4.50 s, 2H).
  • 14
  • [ 22282-72-0 ]
  • [ 127838-58-8 ]
YieldReaction ConditionsOperation in experiment
With borane-THF; In tetrahydrofuran; at 0 - 25℃; for 2h; Preparative Example 4.30 4-[(4-iodo- lH-pyrazol- 1 -yl)methyl]py Step 1 : Borane-THF (29 mL, 1.0 M) was added to a solution of 2-oxo-l,2- dihydropyridine-4-carboxylic acid (1 g, 7.19 mmol) in THF (15 mL) at 0 C. The mixture was stirred at 25 C for 2 hours. Methanol was added and the mixture was concentrated under reduced pressure to afford 4-(hydroxymethyl)pyridin-2(lH)-one. MS ESI calc'd. for C6H8 02 [M + H]+ 126, found 126. XH NMR (400 MHz, CD3OD) delta 7.40 (d, J= 6.8 Hz, 1H), 6.58 (s, 1H), 6.38 (d, J= 6.4 Hz, 1H), 4.52 (s, 2H).
  • 15
  • [ 127838-58-8 ]
  • 4‐(bromomethyl)‐1,2‐dihydropyridin‐2‐one [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With hydrogen bromide; at 110℃; for 16h; A mixture of 4- (hydroxymethyl)pyridin-2(1H)-one (500 mg, 4.00 mmol) and HBr (1 ml, 8.84 mmol) was heated to 110 C for 16 h. The mixture was concentrated under reduced pressure, the residue was treated with water and the resulting suspension was filtered to give 4-(bromomethyl)pyridin-2(lH)-one as a white solid (368 mg, 49%). MS (ES+) C6H6BrNO requires: 187, found: 188 [M+H]+.
With hydrogen bromide; at 0 - 110℃; for 3h; Step 2: Hydrobromic acid (2 mL) was added to a solution of 4-(hydroxymethyl)pyridin- 2(lH)-one (200 mg, 1.6 mmol) was at 0 C. The mixture was stirred at 1 10 C for 3 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc/MeOH) to afford the 4- (bromomethyl)pyridin-2(lH)-one. MS ESI calc'd. for C6H7BrNO [M + H]+ 188 and 190, found 188 and 190. NMR (400 MHz, DMSO-i) delta 1 1.55 (s, 1H), 7.36 (d, J= 6.8 Hz, 1H), 6.39 (s, 1H), 6.17 (d, J= 6.8 Hz, 1H), 4.45 (s, 2H).
With hydrogen bromide; In water; at 100℃; for 16h; A mixture of 4- (hydroxymethyl)pyridin-2(lH)-one (150 mg, 1.2 mmol) and aqueous hydrogen bromide (48%, 10 mL) was heated to 100C for 16 h. The reaction mixture wascooled to RT and concentrated under reduced pressure to afford 4- (bromomethyl)pyridin-2(lH)-one as a brown solid (225 mg, 100%), which was directly used for next step without further purification. MS (ES+) 06Eta6BetaGammaNuOmicron requires: 188, found: 189 [M+H]+.
  • 16
  • [ 127838-58-8 ]
  • 4-((4-iodo-1H-pyrazol-1-yl)methyl)pyridin-2(1H)-one [ No CAS ]
  • 17
  • [ 127838-58-8 ]
  • [ 1570496-11-5 ]
  • 18
  • [ 127838-58-8 ]
  • [ 1570496-12-6 ]
  • [ 1570496-14-8 ]
  • 19
  • [ 127838-58-8 ]
  • [ 1571032-47-7 ]
  • 20
  • [ 127838-58-8 ]
  • [ 1571023-18-1 ]
 

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