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Structure of 893440-50-1

Chemical Structure| 893440-50-1

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Product Details of [ 893440-50-1 ]

CAS No. :893440-50-1
Formula : C12H19BN2O3
M.W : 250.10
SMILES Code : NC1=CC(B2OC(C)(C)C(C)(C)O2)=CN=C1OC
MDL No. :MFCD12923427
InChI Key :KYYKGOURQXPERA-UHFFFAOYSA-N
Pubchem ID :59557920

Safety of [ 893440-50-1 ]

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

Computational Chemistry of [ 893440-50-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.58
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 71.61
TPSA ?

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

66.6 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

1.46
Log Po/w (WLOGP)?

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

0.98
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.

0.13
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

0.61
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.63

Water Solubility

Log S (ESOL):?

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

-2.43
Solubility 0.94 mg/ml ; 0.00376 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.46
Solubility 0.858 mg/ml ; 0.00343 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < 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

-3.4
Solubility 0.1 mg/ml ; 0.0004 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

Yes
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.

-6.79 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

0.0
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<0.0
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)

3.01

Application In Synthesis of [ 893440-50-1 ]

* 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 [ 893440-50-1 ]

[ 893440-50-1 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 893440-50-1 ]
  • [ 124-63-0 ]
  • [ 1083326-75-3 ]
YieldReaction ConditionsOperation in experiment
With pyridine; at 20℃; for 18h; To a solution of 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3- pyridinamine (0.5 g, 1.999 mmol) in pyridine (5 ml) was added methanesulphonyl chloride (0.309 ml, 4.00 mmol) and the mixture stirred at 20 0C for 18 hr when the solvent was removed in vacuo. The residue was partitioned between saturated sodium bicarbonate solution (10ml) and dichloromethane (20ml), separated by hydrophobic frit and purified by silica (7Og) cartridge on Flashmaster Il using a gradient of dichloromethane and methanol to give the title compound as a brown solid (0.46g). LCMS (Method A) Rt 0.98mins, MH+ 329.
With pyridine; at 20℃; for 18h; To a solution of 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3- pyridinamine (0.5 g) in pyridine (5 ml) was added methanesulphonyl chloride (0.309 ml) and the mixture stirred at RT for 18 h when the solvent was removed in vacuo. The residue was partitioned between saturated sodium bicarbonate solution (10 ml) and DCM (20 ml), separated by hydrophobic frit and purified by silica (70g) cartridge on Flashmaster II using a gradient of DCM and methanol to give the title compound as a brown solid, 0.46 9-LCMS (method B); Rt = 0.98 min, MH+ = 329.
With pyridine; at 20℃; for 18h; Intermediate 8N-[2-(Methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3- ridinyl]methanesulfonamideTo a solution of 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3- pyridinamine (0.5 g, 1.999 mmol) in pyridine (5 ml) was added methanesulphonyl chloride (0.309 ml, 4.00 mmol) and the mixture stirred at 20 C for 18 hr then the solvent was removed in vacuo. The residue was partitioned between saturated sodium bicarbonate solution (10 ml) and dichloromethane (20 ml), separated by hydrophobic frit and purified by silica gel chromatography, eluting with a gradient of dichloromethane and methanol to give the title compound as a brown solid (0.46g).LCMS (Method A): Rt 0.98mins, MH+ 329.
With pyridine; at 0℃;Inert atmosphere; 2-Methoxy-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-3-amine (940 mg, 3.76 mol) was dissolved in 20 mL pyridine. The mixture was submitted to three vacuum-argon cycles and was cooled at 0C with an ice bath. Methanesulfonyl chloride (600 muIota, 7.75 mol) was added dropwise and the reaction mixture was stirred overnight. The solvent was concentrated and the residue was partitioned between dichloromethane and a saturated sodium bicarbonate solution. The organic phase was dried over sodium sulphate and evaporated under reduced pressure. The semi-solid was crystallized with diethyl ether and isopropyl ether to obtain a solid that was filtered and dried in the oven to give 720 mg (58% yield) of the final compound as a mixture of boronic acid and boronate. Purity 100%.LRMS (m/z): 329 (M+1 )+.
0.46 g With pyridine; at 20℃; for 18h; N-[2-(Methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide To a solution of 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine (0.5 g, 1.999 mmol) in pyridine (5 ml) was added methanesulphonyl chloride (0.309 ml, 4.00 mmol) and the mixture stirred at 20 C. for 18 hr when the solvent was removed in vacuo. The residue was partitioned between saturated sodium bicarbonate solution (10 ml) and dichloromethane (20 ml), separated by hydrophobic frit and purified by silica (70 g) cartridge on Flashmaster II using a gradient of dichloromethane and methanol to give the title compound as a brown solid (0.46 g). LCMS (Method A) Rt 0.98 mins, MH+ 329.
With pyridine; at 20℃; for 18h; Intermediate 30N-[2-(Methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3- pyridinyljmethanesulfonamide To a solution of 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3- pyridinamine (0.5 g, 1.999 mmol) in pyridine (5 ml) was added methanesulphonyl chloride (0.309 ml, 4.00 mmol) and the mixture stirred at 20 0C for 18 hr when the solvent was removed in vacuo. The residue was partitioned between saturated sodium bicarbonate solution (10 ml) and DCM (20 ml), separated by hydrophobic frit and purified by silica (7Og) cartridge on Flashmaster Il using a gradient of DCM and methanol to give the title compound as a brown solid (0.46 g). LCMS (Method B) Rt 0.98mins, MH+ 329.
With pyridine; at 20℃; for 18h; Intermediate 8N-[2-(Methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3- pyridinyljmethanesulfonamideTo a solution of 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3- pyridinamine (0.5 g, 1.999 mmol) in pyridine (5 ml) was added methanesulphonyl chloride (0.309 ml, 4.00 mmol) and the mixture stirred at 20 0C for 18 hr then the solvent was removed in vacuo. The residue was partitioned between saturated sodium bicarbonate solution (10 ml) and dichloromethane (20 ml), separated by hydrophobic frit and purified by silica gel chromatography, eluting with a gradient of dichloromethane and methanol to give the title compound as a brown solid (0.46g). LCMS (Method A): Rt 0.98mins, MH+ 329.

  • 2
  • [ 1083168-94-8 ]
  • [ 893440-50-1 ]
YieldReaction ConditionsOperation in experiment
95% With hydrogen;Raney-Ni; In methanol; for 2.0h; The mixture of 2-methoxy-3-nitro-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl) pyridine (300mg, 1 .1 mmol) and Raney-Ni(I Omg) in MeOH (10mL) was subject to H2 and stirred for 2h. After filtration, the filtrate was concentrated to give the title compound as a white solid (261 mg). Yield: 95.0%.
95% With hydrogen; In methanol; for 2.0h; The mixture of <strong>[1083168-94-8]2-methoxy-3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine</strong> (300 mg, 1.1 mmol) and Raney-Ni (10 mg) in MeOH (10 mL) was subject to H2 and stirred for 2 h. After filtration, the filtrate was concentrated to give the title compound as a white solid (261 mg). Yield: 95.0%.
89% With hydrogen;Raney-Ni; In methanol; at 20.0℃; for 2.0h; To the solution of 2-methoxy-3-nitro-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan- 2-yl) pyridine (500 mg, 1 .79 mmol) in MeOH (50 ml_) was added Raney-Ni (50 mg). The reaction mixture was stirred at room temperature under H2 for 2h. Then the solid was filtered off, and the solvent was removed to afford 2-methoxy-5-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-3-amine in 89% yield (400 mg). m/z 251 (M+H)+.
89% With hydrogen; In methanol; at 20.0℃; for 2.0h; To the solution of <strong>[1083168-94-8]2-methoxy-3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine</strong> (500 mg, 1.79 mmol) in MeOH (50 mL) was added Raney-Ni (50 mg). The reaction mixture was stirred at room temperature under H2 for 2 h. Then the solid was filtered off, and the solvent was removed to afford 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine in 89% yield (400 mg). m/z 251 (M+H)+.

  • 3
  • [ 38222-83-2 ]
  • [ 893440-50-1 ]
  • [ 358-23-6 ]
  • [ 1366050-38-5 ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at -20℃; for 2.0h; To a solution of 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridin-3-amine (100 mg, 0.4 mmol) and <strong>[38222-83-2]2,6-di-tert-butyl-4-methylpyridine</strong> (115 mg, 0.56 mmol) in dichloromethane (5 mL) was added trifluoromethanesulfonic anhydride (147 mg, 0.52 mmol) drop wise at ?20° C., and the mixture was stirred at this temperature for 2 h. Solvent was removed in vacuo and the residue was used in the next step without further purification (141 mg). Yield: 92.0percent.
  • 4
  • [ 893440-50-1 ]
  • [ 124-63-0 ]
  • [ 1083326-75-3 ]
  • (6-methoxy-5-(methylsulfonamido)pyridin-3-yl)boronic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; at 0℃;Inert atmosphere; 2-Methoxy-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-3-amine (940 mg, 3.76 mol) was dissolved in 20 mL pyridine. The mixture was submitted to three vacuum-argon cycles and was cooled at 0C with an ice bath. Methanesulfonyl chloride (600 muIota, 7.75 mol) was added dropwise and the reaction mixture was stirredovernight. The solvent was concentrated and the residue was partitioned between dichloromethane and a saturated sodium bicarbonate solution. The organic phase was dried over sodium sulphate and evaporated under reduced pressure. The semi-solid was crystallized with diethyl ether and isopropyl ether to obtain a solid that was filtered and dried in the oven to give 720 mg (58% yield) of the final compound as a mixture of boronic acid and boronate. Yield 100%. LRMS (m/z): 329 (M+1 )+.
  • 5
  • [ 893440-50-1 ]
  • [ 62484-29-1 ]
  • C14H10Cl2N4O [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% With potassium fluoride; tris-(dibenzylideneacetone)dipalladium(0); tri tert-butylphosphoniumtetrafluoroborate; In tetrahydrofuran; water; at 50℃; for 7h;Inert atmosphere; ] A mixture of compound 1 -d (prepared according to the method disclosed in Heterocycles, 2012, pages 1417- 1426) (480 mg, 2.068 mmol), compound 1-c (prepared according to the method disclosed in WO 2009/147 187 Al) (510 mg, 2.068 mmol), Pd2(dba)3 (42 mg, 0.046 mmol), [(t13u) 3PH]13F4 (60 mg, 0.207 mmol), potassium flouride (470 mg, 8.276 mmol), tetrahydrofuran (15 mE) and water (1.5 mE) was heated to 50 C. under nitrogen gas atmosphere and stirred for 7 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatograph (elution system: dichloromethane/ethanol=20/1) to give compound 1-c (260 mg, 39%). EC-MS(ESI): mlz=321.0 (M+H)
  • 6
  • [ 960613-96-1 ]
  • [ 893440-50-1 ]
  • [ 199609-62-6 ]
  • [ 1414463-32-3 ]
YieldReaction ConditionsOperation in experiment
63% Reaction performed in parallel in 7 batches of 500 mg of 6 in a carrousel. From 3-bromo-5-chloropyrazolo[1,5-a]pyrimidine (6) (500 mg, 2.151 mmol), (5-amino-6-methoxypyridin-3-yl)boronic acid pinacol ester (538 mg, 2.151 mmol,), PdCl2(PPh3)2 (75 mg) in 1,2-DME (9 mL) and Na2CO3 (aq sat sol, 4.3 mL) heated at 80 C in semi-pressure tubes for 30 min. Then <strong>[199609-62-6]3-(N-Boc-aminomethyl)phenylboronic acid</strong> (675 mg, 2.689 mmol,) PdCl2(PPh3)2 (45 mg) were added and the mixture was heated at 100 C for 5 h. Purification of all batches together using gradient from 0% to 100% of EtOAc in cHex afforded 20 (4.23 g, 63%). LCMS (ESI): Rt = 4.68 min, m/z = 447.10 [M+ H]+.
 

Historical Records

Technical Information

Categories

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[ 893440-50-1 ]

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