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Chemical Structure| 75907-74-3 Chemical Structure| 75907-74-3

Structure of 75907-74-3

Chemical Structure| 75907-74-3

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Product Details of [ 75907-74-3 ]

CAS No. :75907-74-3
Formula : C8H12N2O
M.W : 152.19
SMILES Code : OCC1=NC(C)=C(C)N=C1C
MDL No. :MFCD08059950
InChI Key :LAXOCXPBJXIBHO-UHFFFAOYSA-N
Pubchem ID :12629702

Safety of [ 75907-74-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 75907-74-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 43.06
TPSA ?

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

46.01 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.53
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

0.13
Log Po/w (WLOGP)?

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

0.74
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.

-0.33
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

2.04
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.82

Water Solubility

Log S (ESOL):?

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

-1.2
Solubility 9.53 mg/ml ; 0.0626 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.

-0.65
Solubility 33.9 mg/ml ; 0.223 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

-2.63
Solubility 0.359 mg/ml ; 0.00236 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.

-7.14 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)

2.07

Application In Synthesis of [ 75907-74-3 ]

* 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 [ 75907-74-3 ]

[ 75907-74-3 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 75907-74-3 ]
  • [ 186534-02-1 ]
YieldReaction ConditionsOperation in experiment
93.9% With manganese(IV) oxide; In ethanol; for 12h;Reflux; Reaction step 2-hydroxymethyl-3,5,6-trimethylpyrazine (9.5 g, 62.5 mmol) was sequentially added to a 250 mL three-necked flask,MnO2 (16.2 g, 187.5 mmol),Ethanol 100mL,Reflux 12h,TLC (petroleum ether - ethyl acetate 2: 1) detection reaction is almost complete,cool down,Filtering to obtain filtrate,Ethanol recovery under reduced pressure,To give a yellow solid,Purification by silica gel column chromatography (petroleum ether-ethyl acetate 4: 1)3,5,6-trimethylpyrazine-2-carbaldehyde as a pale yellow solid,The yield was 93.9%
93.9% With manganese(IV) oxide; In ethanol; for 12h;Reflux; Were added 2-hydroxymethyl-3,5,6-trimethyl pyrazine in 250mL three-necked flask (9.5g, 62.5mmol), MnO2(16.2g, 187.5mmol), ethanol 100mL, refluxed for 12h, TLC (petroleum ether - ethyl acetate 2: 1) detecting the reaction is substantially complete, cooled, filtered, recovering ethanol under reduced pressure to give a yellow solid by silica gel column chromatography (petroleum ether - ethyl acetate 4: 1) to give 8.8 g of a pale yellow solid, yield 93.9%.
90% With manganese(IV) oxide; In ethanol; for 6h;Reflux; Weigh 2-hydroxymethyl-3,5,6-trimethylpyrazine (3.0 g, 25 mmol),Dissolved in 50mL of absolute ethanol,Manganese dioxide powder (4.34 g, 50 mmol) was added with stirring.The reaction was carried out under heating and reflux for 6 h.Cooling the reaction solution,Add diatomaceous earth and filter under reduced pressure.After the filter cake is rinsed with ethanol,Merged with the filtrate,Evaporation of the solvent gave a pale yellow solid.Is a crude product of 3,5,6-trimethylpyrazine-2-formaldehyde,Then perform rapid column chromatography separation,Light yellow solid,That is pure 3,5,6-trimethylpyrazine-2-carboxaldehyde,Yield 90%,Melting point 84-85 C.
75% With manganese(IV) oxide; In ethanol; at 84℃; for 2h; The obtained 7.5 g of TMP-OH (49.3 mmol) was dissolved in 50 ml of absolute ethanol to add active manganese dioxide.(6.4g, 73.6mmol) was oxidized and reacted in an oil bath at 84 C for 2 h. After the TLC reaction was completed,The reaction solution was carefully filtered with a five-layer filter paper while hot, and the manganese dioxide powder was removed.After filtration, a clear filtrate was obtained, which was evaporated to dryness under reduced pressure on a rotary evaporator. Wet loading column chromatography:The mobile phase EA:PE (1:5) was separated and purified, and the fraction was monitored by TLC. Collecting the compound 1a-4 fraction,Combine the same fraction and distill it to obtain a crystalline white solid.5.5g (36.7mmol),[M+H]+=151 is 1a-4 (TMP-CHO), yield 75%.
70% With manganese(IV) oxide; In chloroform; for 6h;Reflux; Compound 1a (6.08 g, 40 mmol) was dissolved in CHCl3 (60 mL),MnO2 (24 g, 280 mmol) was added, and the mixture was refluxed for 6 h, cooled, filtered, and concentrated. The crude productwas purified by column chromatography and eluted with ethyl acetate-petroleum ether (1:6) to yield 1b as bright yellowcrystals (4.2 g, 70%), mp 86C. ESI-MS m/z 151 [M + 1]+, C8H10N2O. 1H NMR (500 MHz, CDCl3, , ppm): 10.10 (1H, s,CHO), 2.75 (3H, s, CH3), 2.56 (6H, s, CH3 2). 13C NMR (125 MHz, CDCl3, , ppm): 21.39, 22.18, 141.91, 149.98, 151.54,155.45, 194.33.
66% With manganese(IV) oxide; In ethanol; for 3h;Reflux; In a 50 ml round-bottom flask the compound TMP-OH (1.52 g 10 mmol) was added and dissolved in 20 mL of anhydrous ethanol active manganese dioxide (2.61 g 30 mmol) was added heated to reflux for 3 hours and monitored by TLC until the starting material completely comsumed and the resulting material was filtered and concentrated and separated with column chromatography eluted with ethyl acetate /petroleum ether (11) to give the compound TMP-CHO as a white solid (0.99 g 66) .
66% With manganese(IV) oxide; In ethanol; for 3h;Reflux; In a 50 ml round-bottom flask, the compound TMP-OH (1.52 g, 10 mmol) was added and dissolved in 20 mE of anhydrous ethanol, active manganese dioxide (2.61 g, 30 mmol) was added, heated to reflux for 3 hours, and monitored by TEC until the starting material completely consumed, and the resulting material was filtered and concentrated, and separated with colunm chromatography eluted with ethyl acetate/petroleum ether (1:1) to give the compound TMP-CHO as a white solid (0.99 g, 66%).
With manganese(IV) oxide; In dichloromethane; at 20℃; for 72h; A suspension of 3,5,6-trimethylpyrazine-2-yl)methanol (see Bioorg. Med. Chem. 2007, 15, 3315; 14.8 g, 97.2 mmol) and manganes(IV) oxide (30.0 g) in dichloromethane was stirred at room temperature for 3 days. The reaction mixture was filtrated through Celite with dichloromethane. The filtrate was combined and concentrated in vacuo to give 3,5,6-trimethylpyrazine-2-carbardehyde. MS (APCI): m/z 151 (M+H).

 

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Technical Information

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