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Chemical Structure| 4399-47-7 Chemical Structure| 4399-47-7

Structure of 4399-47-7

Chemical Structure| 4399-47-7

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Product Details of [ 4399-47-7 ]

CAS No. :4399-47-7
Formula : C4H7Br
M.W : 135.00
SMILES Code : BrC1CCC1
MDL No. :MFCD00001317
InChI Key :KXVUSQIDCZRUKF-UHFFFAOYSA-N
Pubchem ID :78110

Safety of [ 4399-47-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319-H335
Precautionary Statements:P210-P261-P305+P351+P338
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 4399-47-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 5
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 27.1
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.92
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

1.9
Log Po/w (WLOGP)?

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

1.93
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.

2.03
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

2.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.01

Water Solubility

Log S (ESOL):?

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

-1.87
Solubility 1.8 mg/ml ; 0.0134 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.

-1.52
Solubility 4.05 mg/ml ; 0.03 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

-1.58
Solubility 3.57 mg/ml ; 0.0264 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.

-5.77 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

3.0
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)

3.01

Application In Synthesis of [ 4399-47-7 ]

* 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 [ 4399-47-7 ]

[ 4399-47-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 4399-47-7 ]
  • [ 14173-30-9 ]
  • [3-(cyclobutyloxy)pyridin-2-yl]methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In water; N,N-dimethyl-formamide; a 3-Cyclobutyloxy-2-pyridinemethanol 3-Hydroxy-2-(hydroxymethyl)pyridine hydrochloride (1.57 g, 0.009 mol), potassium carbonate (8.09 g, 0.058 mol) and cyclobutyl bromide (5.0 g, 0.037 mol) were stirred together under nitrogen in N,N-dimethylformamide (20 ml) at 50 C. overnight. Water (40 ml) was added, and the resultant solution was acidified to pH 1 with hydrochloric acid (5 N). The solution was washed with dichloromethane (3*100 ml), basified to pH 14 with sodium hydroxide solution (4 N), and extracted with dichloromethane (3*100 ml). The organic layers from the extraction were combined, washed with water (1*100 ml), dried over magnesium sulfate and concentrated in uacuo to give a dark brown solid which was recrystallized from hexane to give the title compound (0.44 g). 1H NMR (250 MHz, CDCl3) δ 1.61-1.81 (1H, m), 1.86-1.91 (1H, m), 2.09-2.22 (2H, m), 2.39-2.51 (2H, m), 4.31 (1H, br s), 4.66 (1H, m), 4.74 (1H, s), 6.97 (1H, m), 7.07-7.17 (1H, m), 8.13 (1H, m); MS (ES+) m/e 180 [MH]+.
  • 2
  • [ 55717-45-8 ]
  • [ 4399-47-7 ]
  • [ 1177269-07-6 ]
YieldReaction ConditionsOperation in experiment
70% With potassium carbonate; In N,N-dimethyl-formamide; at 60 - 80℃; for 19.0h; 2-Bromo-5-hydroxypyridine (1.0 g, 5.75 mmol), bromocyclobutane (0.783 mL, 8.33 mmol), and potassium carbonate (1.59 g, 11.5 mmol) were mixed in DMF (11 mL) and stirred at 60 C. for 5 h, then at 80 C. for 14 h. The reaction mixture was diluted with EtOAc and washed with water, saturated NaHCO3, and brine. The organic layer was dried (Na2SO4) and concentrated. The crude product was purified by ISCO (40 g), eluting with a gradient of EtOAc/hexane 0-10% to provide to give 2-bromo-5-cyclobutoxypyridine (0.92 g, 4.0 mmol, 70% yield) as white solid. ESI (M+1) 229.9.
69.9% With potassium carbonate; In hexane; N,N-dimethyl-formamide; Step 1: Synthesis of 2-bromo-5-cyclobutoxypyridine The mixture of 2-bromo-5-hydroxypyridine (1 g, 5.75 mmol), bromocyclobutane (0.783 mL, 8.33 mmol) and potassium carbonate (1.589 g, 11.49 mmol) in DMF (11.5 mL) was stirred at 60 C. for 5 h, then at 80 C. for 14 h. The reaction mixture was diluted with EtOAc and washed with water, saturated NaHCO3, and brine. The organic layer was dried (Na2SO4) and concentrated. The crude product was purified by ISCO (40 g), eluting with a gradient of EtOAc/hexane 0-10% to provide to give 2-bromo-5-cyclobutoxypyridine (0.916 g, 4.02 mmol, 69.9% yield) as white solid. MS: M+ 228, 230. C9H10BrNO, MW=228.09
With potassium carbonate; In N,N-dimethyl-formamide; at 60 - 80℃; for 14.0h; 2-bromo-5-(cyclobutyloxy)pyridine 6-Bromo-3-pyridinol (1 g, 5.75 mmol), bromocyclobutane (0.812 ml, 8.32 mmol) and potassium carbonate (1.589 g, 11.49 mmol) were mixed in N,N-dimethylformamide (11.5 ml) and were stirred at 60 C. for 5 hours then at 80 C. for 9 hours. The reaction was diluted with ethyl acetate (120 ml) and washed with water (40 ml), saturated aqueous sodium hydrogencarbonate (30 ml) and brine (30 ml). The organic phase was passed through a hydrophobic PTFE frit and evaporated. The crude was purified on silica eluding with cyclohexane/ethyl acetate: 99/1 to 9/1 to afford the title compound (820 mg), which eluted at cyclohexane/ethyl acetate: 95/5. 1H NMR (400 MHz, CDCl3): δ 7.91 (1H, d), 7.35 (1H, d), 7.02 (1H, dd), 4.64 (2H, qui), 2.39-2.53 (2H, m), 2.11-2.25 (2H, m), 1.84-1.97 (1H, m), 1.64-1.80 (1H, m); UPLC-MS: 0.78 min, 228, 230 [M+H]+; TLC: Rf=0.74 (cyclohexane/ethyl acetate: 3/1, silica).
  • 3
  • [ 22300-52-3 ]
  • [ 4399-47-7 ]
  • C6H7Br2N3 [ No CAS ]
  • 4
  • [ 269410-08-4 ]
  • [ 4399-47-7 ]
  • [ 1002309-48-9 ]
YieldReaction ConditionsOperation in experiment
5.21% 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (300 mg, 1.55 mmol) was dissolved in DMF (5 mL) at 0 C under Ar. NaH (60% in oil, 40.8 mg, 1.70 mmol) was added portionwise, and the reaction mixture was then stirred for 20 minutes at rt. A solution of bromocyclobutane (209 mg, 1.55 mmol) in 1 mL of DMF was added, and stirring was continued 2 h at rt. The reaction mixture was quenched with saturated aq. NH4Cl, and then extracted 3x with EtOAc, washed with brine, dried with Na2SO4, filtered and concentrated. The product was purified by silica gel chromatography to provide pyrazole boronate 20A (40 mg, 5.21 %) . MS (ESI): m/z 249.0 (M+H).
4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (CAS 269410-08-4, 1.20 g, 6.18 mmol) was dissolved in DMF (23 mL) and sodium hydride (0.81 g, 18.6 mmol) was added at room temperature (rt). After 10 min, cyclobutyl bromide (2.51 g, 18.6 mmol) was added and the mixture stirred for 2 g at 50 C and further 16 h at rt. The mixture was partitioned between water and ethyl acetate, extracted with ethyl acetate, and the combined organic layers washed with water, dried (Na2SC>4) and concentrated. The crude product (1.14 g, 87% purity, 64% yield) was used without further purification.
  • 5
  • [ 4399-47-7 ]
  • [ 14521-81-4 ]
  • 1-cyclobutyl-3-fluoro-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
<strong>[14521-81-4]3-fluoro-1H-pyrazole</strong> (150 mg, 2.91 mmol) were dissolved in DMF (10 mL) at RT. Sodium hydride (152 mg, 3.49 mmol, 1 .2 eq) was added and the mixture stirred for 10 min. Then cyclobutylbromide (0.82 mL, 8.71 mmol, 3 eq. ) was added and the mixture stirred for 2 h at 50 C. After cooling to RT, the mixture was poured into water and extracted 4x with ethyl acetate. The combined organic layers were washed with brine, dried with sodium sulfate and the solvents removed in vacuo. The crude product afforded no further purification: 400 mg (98% of theory) pale yellow oil. 1H NMR (400 MHz, DMSO-d6) delta [ppm] 1 .68 - 1 .79 (m, 2H), 2.28 -2.43 (m, 4H), 4.88 (quint, 1 H), 5.91 (dd, 1 H), 7.71 (t, 1 H). LCMS (method 1 ): Rt = 0.84 min; MS (ESIPos) m/z = 141 (M+H)
 

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