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Structure of 847818-55-7

Chemical Structure| 847818-55-7

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Product Details of [ 847818-55-7 ]

CAS No. :847818-55-7
Formula : C4H7BN2O2
M.W : 125.92
SMILES Code : CN1N=CC(B(O)O)=C1
MDL No. :MFCD09414709
InChI Key :RYGOBSYXIIUFOR-UHFFFAOYSA-N
Pubchem ID :11263501

Safety of [ 847818-55-7 ]

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

Computational Chemistry of [ 847818-55-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 5
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 33.31
TPSA ?

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

58.28 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

-0.86
Log Po/w (WLOGP)?

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

-1.9
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.

-1.79
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

-2.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-1.33

Water Solubility

Log S (ESOL):?

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

-0.42
Solubility 47.4 mg/ml ; 0.377 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.

0.12
Solubility 165.0 mg/ml ; 1.31 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

0.35
Solubility 285.0 mg/ml ; 2.26 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.

-7.68 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

1.0 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)

1.81

Application In Synthesis of [ 847818-55-7 ]

* 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 [ 847818-55-7 ]

[ 847818-55-7 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 53848-17-2 ]
  • [ 847818-55-7 ]
  • 2-methyl-6-(1-methyl-1<i>H</i>-pyrazol-4-yl)-phenylamine [ No CAS ]
  • 2
  • [ 1403257-80-6 ]
  • [ 847818-55-7 ]
  • [ 1403255-78-6 ]
YieldReaction ConditionsOperation in experiment
50% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; Example 109 Synthesis of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methyl-5-(1-methyl-1H-pyrazol-4-yl)benzamide To a stirred solution of <strong>[1403257-80-6]5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzamide</strong> (0.2 g, 0.42 mmol) and (1-methyl-1H-pyrazol-4-yl)boronic acid (0.105 g, 0.505 mmol) in dioxane/water mixture (5 mL+1 mL), Na2CO3 (0.16 g, 1.51 mmol) was added and solution purged with argon for 15 min. Pd (PPh3)4 (0.048 g, 0.042 mmol) was then added and the reaction mixture again purged with argon for 10 min. The reaction mixture was heated at 100 C. for 2 h. The reaction mixture was then diluted with water and extracted with 10% MeOH/DCM. The combined extracts were dried over Na2SO4 and the solvent removed under reduced pressure to afford the crude product which was purified by column chromatography to afford the title compound (0.100 g, 50%). LCMS: 478.20 (M+1)+; HPLC: 95.82% ( 254 nm) (Rt; 4.322; Method: Column: YMC ODS-A 150 mm*4.6 mm*5mu; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 muL, Col. Temp.: 30 C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) delta 11.45 (s, 1H), 8.12 (s, 1H), 8.10 (t, 1H), 7.81 (s, 1H), 7.33 (s, 1H), 7.13 (s, 1H), 5.86 (s, 1H), 4.27 (d, 2H, J=4.8 Hz), 3.81-3.83 (m, 5H), 3.21-3.26 (m, 2H), 2.98-3.08 (m, 3H), 2.20 (s, 3H), 2.17 (s, 3H), 2.10 (s, 3H), 1.63-1.66 (m, 2H), 1.48-1.52 (m, 2H), 0.86 (t, 3H, J=7.2 Hz).
  • 3
  • [ 33930-63-1 ]
  • [ 847818-55-7 ]
  • 2-methyl-4-(1-methylpyrazol-4-yl)isoquinolin-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 120℃; for 1.0h;Inert atmosphere; Microwave irradiation; For 3 min, N2 was bubbled through a mixture of <strong>[33930-63-1]4-bromo-2-methylisoquinolin-1(2H)-one</strong> (54 mg, 0.23 mmol), (1-methylpyrazol-4-yl)boronic acid (31 mg, 0.25 mmol), aqueous 2M Na2CO3 (0.375 mL) and Pd(dppf)Cl2 (8 mg, 0.01 mmol) in 1,4-dioxane (1.5 mL) which was then microwaved at 120° C. for 1 h. Work up in a manner similar to Example 18, step 3, and two successive silica gel chromatographies, eluting with 15-80percent EA in hexane over 6 min and continuing 80percent isocratic EA followed by a second chromatography 15-100percent EA in hexane over 6 min and continuing 100percent isocratic EA gave the title compound (28 mg, 0.12 mmol) as a cream solid in 51percent yield. 1H NMR (400 MHz, DMSO-d6) delta ppm 3.54 (s, 3H) 3.92 (s, 3H) 7.50 (s, 1H) 7.55 (ddd, J=8.02, 5.87, 2.27 Hz, 1H) 7.60-7.64 (m, 1H) 7.70-7.80 (m, 2H) 7.95 (s, 1H) 8.31 (d, J=7.83 Hz, 1H). LCMS (M+H)+ 240.
  • 4
  • [ 1480-65-5 ]
  • [ 847818-55-7 ]
  • [ 1427473-70-8 ]
YieldReaction ConditionsOperation in experiment
77% With potassium phosphate; palladium diacetate; XPhos; In 1,4-dioxane; water; at 100℃; for 12h;Inert atmosphere; Reflux; General procedure: Typical procedure 1: a mixture of <strong>[1480-65-5]5-chloro-2-fluoropyridine</strong> 5a(6.60 g, 50.2 mmol), (1-methyl-1H-pyrazol-4-yl)boronic acid(6.30 g, 50.1 mmol), Pd(OAc)2 (0.46 g, 2.1 mmol), 2-dicyclohexylphosphino-20,40,60-triisopropylbiphenyl (1.99 g, 4.1 mmol), and K3PO4 (26.30 g, 123.7 mmol) in dioxane/water (80 mL/8 mL)was stirred at 100 C under N2 atmosphere until the reaction wascompleted by TLC. After the solution was concentrated underreduced pressure, the product was purified via column chromatographyto afford compound 6a (6.80 g, 77percent). 1H NMR (400 MHz,CDCl3, ppm) d 8.22?8.13 (m, 3H), 7.88 (d, J = 0.4 Hz, 1H), 7.30(d, J = 6.8 Hz, 1H) 3.90 (s, 3H). MS m/z (ESI): [M+H]+ 178.1
  • 5
  • [ 141-30-0 ]
  • [ 847818-55-7 ]
  • [ 943541-20-6 ]
YieldReaction ConditionsOperation in experiment
70% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 80℃; for 10h;Inert atmosphere; o a 250 ml flask of the three-port adding dioxane (67 ml) and water (27 ml) as the solvent, then adding 3,6- [...] (2.68g, 18mmol), potassium carbonate (6.0g, 43 . 5mmol), 1-methylpyrazole-4-boronic acid pinacone ester (2.99g, 14 . 4mmol), [ 1,1 '-bis (diphenylphosphino) ferrocene] palladium dichloride (0.7g, 0 . 96mmol), after the replacement of nitrogen, raising the temperature to 80 C. Reaction 10 after two hours, concentrating the reaction liquid, column chromatography separation, to obtain strawcoloured solid 3-chloro-6 - (1-methyl -1H-pyrazol-4-yl) pyridazine (HJ-8) 1.96g, yield 70%
  • 6
  • [ 1458-01-1 ]
  • [ 847818-55-7 ]
  • methyl 3,5-diamino-6-(1-methyl-1H-pyrazol-4-yl)pyrazine-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; toluene;Inert atmosphere; Reflux; General procedure: <strong>[1458-01-1]Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate</strong> 2 (1 eq.) was combined with K2CO3 (10 eq.), the appropriate (het)aryl boronic acid (1.5 eq.) and Pd(PPh3)4 (5 mol%) in a two-neck round bottom flask. The flask was connected to a condenser and purged with nitrogen. A 4:1 mixture of anhydrous toluene: MeOH (60 mL) was added via syringe and the reaction mixture was heated at reflux for 0.5-18 h. The mixture was allowed to cool to room temperature and filtered through Celite (10 x 3 cm, eluting with 3 x 20 mL EtOAc). The filtrate was evaporated to dryness and the residue purified by silica gel flash column chromatography using EtOAc/pet spirit.
 

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