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Chemical Structure| 106157-82-8

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Product Details of [ 106157-82-8 ]

CAS No. :106157-82-8
Formula : C6H7N3O
M.W : 137.14
SMILES Code : CC(C1=NC(N)=NC=C1)=O
MDL No. :MFCD09263814
InChI Key :XDKSEDDZHXZRKQ-UHFFFAOYSA-N
Pubchem ID :13582270

Safety of [ 106157-82-8 ]

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

Computational Chemistry of [ 106157-82-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 36.63
TPSA ?

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

68.87 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.09
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.

0.27
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.

-0.88
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

0.47
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.16

Water Solubility

Log S (ESOL):?

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

-0.99
Solubility 14.2 mg/ml ; 0.103 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.

-0.86
Solubility 18.8 mg/ml ; 0.137 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

-1.6
Solubility 3.45 mg/ml ; 0.0252 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.

-7.23 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)

1.51

Application In Synthesis of [ 106157-82-8 ]

* 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.

  • Upstream synthesis route of [ 106157-82-8 ]
  • Downstream synthetic route of [ 106157-82-8 ]

[ 106157-82-8 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 106157-85-1 ]
  • [ 106157-82-8 ]
YieldReaction ConditionsOperation in experiment
70% at 20℃; for 6 h; A solution of the said amine (17.5 g, 95.5 mmol) in formic acid was stirred at r.t. for 6 hours and concentrated to dryness and the residue was stirred in ethanol (50 mL) and then filtered thus obtaining 1-(2-aminopyrimidin-4-yl)ethanone (9.2 g, 70percent).
70% at 20℃; for 6 h; Example 2 1- (2-AMINOPYRIMIDIN-4-YL)-2-BROMOETHANONE hydrobromide The title compound (a) was prepared by working as described in J. Het. Chem. 1985,22, 1723. A mixture of 3,3-dimethoxy-2-butanone (25 9, 189.16 MMOL) and N, N-DIMETHYLFORMAMIDE DIMETHYLACETAL (22.5 g, 189.16 MMOL) were stirred at 110°C for 30 hours and then distilled (115°C, 1 mmHg) thus obtaining 1-(DIMETHYLAMINO)-4, 4-DIMETHOXYPENT-1-EN-3-ONE, as a yellow solid (27.3 G, 146 mmol, 77percent). Onto a solution of sodium (3.48 g, 151.67 MMOL) in anhydrous ethanol (400 mL), solid guanidine hydrochloride (14.5 G, 151.67 MMOL) was added at r. t. , to give a white suspension into which a solution of 1-(DIMETHYLAMINO)-4, 4-DIMETHOXYPENT-1-EN-3-ONE (28.4 g, 151.67 MMOL) in anhydrous ethanol (50 mL) was added. The mixture was refluxed for 19 hours. After cooling, the precipitate was filtered and washed with ethanol and with plenty of water, thus obtaining a white solid (8.56 G). The ethanolic solutions were concentrated to dryness, taken up with boiling ethyl acetate (1000 mL), filtered while hot and then cooled to yield a second crop. Total amount of 4- (1, 1-DIMETHOXYETHYL) PYRIMIDIN-2-AMINE : 17.66 G, 63. 5percent. A solution of the said amine (17. 5 G, 95.5 MMOL) in formic acid was stirred at r. t. for 6 hours and concentrated to dryness and the residue was stirred in ethanol (50 mL) and then filtered thus obtaining 1- (2-aminopyrimidin-4-yl) ethanone (9.2 g, 70percent). To a solution of 1- (2- aminopyrimidin-4-yl) ethanone (412 mg, 3 MMOL) in glacial acetic acid (1 mL) and 48percent aq. HBr (0.3 mL), bromine (0.153 mL) in acetic acid (0.4 mL) was added and the resulting orange solution was stirred at r. t. for 15 hours. After diluting with ethyl acetate (15 mL) the precipitate was filtered and washed with ethyl acetate thus affording the title compound as a whitish solid (580 mg, 65percent).
70% at 20℃; for 6 h; A solution of the said amine (17.5 g, 95.5 mmol) in formic acid was stirred at r.t. for 6 hours and concentrated to dryness and the residue was stirred in ethanol (50 mL) and then filtered thus obtaining 1-(2-aminopyrimidin-4-yl)ethanone (9.2 g, 70percent).
70% at 20℃; for 6 h; Example 3; 1 -(2-Aminopyrimidin-4-yl)-2-bromoethanone hydrobromi'de; A mixture of 3,3-dimethoxy-2-butanone (25 g, 189.2 mmol) and N1N- dimethylformamide dimethylacetal (22.5 g, 189.2 mmo.) were stirred at 1100C for 30 hours and then distilled (11511C, 1 mmHg) thus obtaining 1-(dimethyiamino)-4,4-dimethoxypent-1-en- 3-oπe, as a yellow solid (27.3 g, 146 mmol, 77percent). Onto a solution of sodium (3.48 g, 151.7 mmol) in anhydrous ethanol (400 mL), solid guanidine hydrochloride (14.5 g, 151.7 mmol) was added at r.t. to give a white suspension into which a solution of 1-(dirnethylamino)-4,4- dimethoxypent-1-eπ-3-one (28.4 g, 151.7 mmo.) in anhydrous ethanol (50 mL) was added. The mixture was refluxed for 19 hours. After cooling, the precipitate was filtered and washed with ethanol and with plenty of water, thus obtaining a white solid (8.5 g). The ethanolic solutions were concentrated to dryness, taken up with boiling ethyl acetate (1000 mL), filtered while hot, and then cooled to yield a second crop. The total amount of 4-(1 ,1- dimethoxyethyl)pyrimidin-2-arnine obtained was 17.7 g, 63.5percent, A solution of the said amine (17.5 g, 95.5 mmol) in formic acid was stirred at room temperature for 6 hours and concentrated to dryness and the residue was stirred in efhanoi (50 mL) and then filtered thus obtaining 1-(2-aminopyrimidiπ-4-yl)ethanone (9.2 g, 70percent). To a solution of the 1-(2- <n="34"/>aminopyrimidin-4-yl)ethanone (412 mg, 3 mmoi) in glacial acetic acid (1 mL) and 48percent aq. HBr (0.3 mL), bromine (0.153 mL) in acetic acid (0.4 mL) was added and the resulting orange solution was stirred at r.t. for 15 hours. After diluting with ethyl acetate (15 mL) the precipitate was filtered and washed with ethyl acetate thus affording the title compound as a whitish solid (580 rng, 65percent).1H NMR (DMSO-d6 / 400 MHz) δ ppm: 4.9 (s, 2 H), 7,0 (d, 2 H), 8.5 (d, 2 H)

References: [1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1723 - 1726.
[2] Patent: US2007/142415, 2007, A1, . Location in patent: Page/Page column 17.
[3] Patent: WO2005/14572, 2005, A1, . Location in patent: Page/Page column 24; 25.
[4] Patent: US2007/142414, 2007, A1, . Location in patent: Page/Page column 19.
[5] Patent: WO2007/96334, 2007, A1, . Location in patent: Page/Page column 32-33.
[6] Patent: WO2004/5279, 2004, A2, . Location in patent: Page 164.
[7] Patent: WO2011/76723, 2011, A1, . Location in patent: Page/Page column 23-24.
  • 2
  • [ 106157-94-2 ]
  • [ 106157-82-8 ]
References: [1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1723 - 1726.
  • 3
  • [ 106157-94-2 ]
  • [ 106157-82-8 ]
References: [1] Patent: WO2011/76723, 2011, A1, .
 

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