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Chemical Structure| 39903-01-0 Chemical Structure| 39903-01-0
Chemical Structure| 39903-01-0

2-Amino-5-bromo-3-pyridinol

CAS No.: 39903-01-0

4.5 *For Research Use Only !

Cat. No.: A153764 Purity: 98%

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Product Details of [ 39903-01-0 ]

CAS No. :39903-01-0
Formula : C5H5BrN2O
M.W : 189.01
SMILES Code : NC1=NC=C(C=C1O)Br
MDL No. :MFCD09744143
InChI Key :YQADLKDQAXAIKW-UHFFFAOYSA-N
Pubchem ID :11694041

Safety of [ 39903-01-0 ]

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

Calculated chemistry of [ 39903-01-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 38.36
TPSA ?

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

59.14 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.25
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

0.84
Log Po/w (WLOGP)?

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

1.14
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.

0.37
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

0.91
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.9

Water Solubility

Log S (ESOL):?

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

-2.03
Solubility 1.75 mg/ml ; 0.00924 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.

-1.66
Solubility 4.09 mg/ml ; 0.0216 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

-1.95
Solubility 2.15 mg/ml ; 0.0114 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.

-6.86 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)

1.76

Application In Synthesis [ 39903-01-0 ]

* 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 [ 39903-01-0 ]

[ 39903-01-0 ] Synthesis Path-Downstream   1~26

  • 1
  • [ 21594-52-5 ]
  • [ 39903-01-0 ]
YieldReaction ConditionsOperation in experiment
98% With sodium hydroxide; water;Heating / reflux; 2: 6-Bromo-3H-oxazolo[4,5-b]pyridin-2-one (21.5 g, 100 mmol) was suspended in NaOH solution (2N, 250 mL, 500 mmol). The mixture was refluxed overnight and a clear solution was obtained. After cooling to room temperature, the reaction solution was neutralized to pH ~7. A lot of CO2 was released and also precipitate was observed. The product was filtered, washed with water, and dried under high vacuum to provide 2-amino-5-bromo-pyridin-3-ol as an off-white solid (17.8 g, 98percent yield).
98% 6-Bromo-3H-oxazolo[4,5-b]pyridin-2-one (21.5 g, 100 mmol) was suspended in NaOH solution (2N, 250 mL, 500 mmol). The mixture was refluxed overnight and a clear solution was obtained. After cooling to room temperature, the reaction solution was neutralized to pH ~7. A lot of C02 was released and also precipitate was observed. The product was filtered, washed with water, and dried under high vacuum to provide 2-amino-5-bromo-pyridin-3-ol as an off-white solid (17.8 g, 98percent yield).
80 - 93% To a solution of 6-bromo-3H-oxazolo[4,5-.pound.]pyridin-2-one (28.0 g, 130 mmol) in MeOH (280 mL) was added a solution of NaOH (28.1 g, 703 mmol) in water (280 mL). The mixture was heated to reflux overnight. The organic solvent was removed in vacuo and the aqueous mixture was adjusted to peta 5-6 with 12 M HCl. The resulting precipitate was isolated by filtration, washed with Et2psi and dried under vacuum at 50 °C overnight to give the title compound (19.6 g, 80percent) as a gray solid: 1H NMR (500 MHz, DMSO-cfc) delta 10.1 (s, IH), 7.46 (d, J= 1.5 Hz, IH), 6.88 (s, IH), 5.70 (s, 2H); ESI MS m/z 190 (M + H)+.; To a suspension of 6-bromo-3H-oxazolo[4,5-]pyridin-2-one (20.0 g, 93.0 mmol) in methanol (200 mL) was added NaOH (20.0 g, 500 mmol) in H2O (200 mL) and the mixture was heated to reflux overnight. After cooling, methanol was removed in vacuo. The aqueous residue was acidified with 3N HCl to pH 5-6. The resulting precipitate was collected by filtration, and dried overnight under vacuum at 45 0C to give the title compound as a tan solid (16.4 g, 93percent): 1H NMR (300 MHz, DMSO-^) delta 10.03 (s, IH), 7.47 (d, J= 2.0 Hz, IH), 6.93 (d, J= 2.0 Hz, IH), 5.72 (s, 2H); ESI MS m/e 188 (M + H)+.
80% [00104] As shown in step 4-iii of Scheme 20, Compound 1012 (34 g, 158.1 mmol) was diluted with 10percent NaOEta(aq) (500 mL), and the resulting mixture was stirred at 100 0C for 6 h. The reaction was cooled to 5 0C, and 6 N HCl was added until a precipitate formed (ca. pH 10). The solid was collected in a fritted funnel, washed with water (200 mL), and dried under vacuum to afford 2-amino-5-bromo-3-hydroxypyridine (Compound 1013, 24.0 g, 80percent yield) as a tan solid: ESMS (M+H) 189, 191; 1H NMR (DMSO-d6) delta 7.5 (s, IH), 6.9 (s, IH), 5.7 (br, 2H).
80% As shown in step 4-iii of Scheme 20, Compound 1012 (34 g, 158.1 mmol) was diluted with 10percent NaOEta(aq) (500 mL), and the resulting mixture was stirred at 100 0C for 6 h. The reaction was cooled to 5 0C, and 6 N HCl was added until a precipitate formed (ca. pH 10). The solid was collected in a fritted funnel, washed with water (200 mL), and dried under vacuum to afford 2-amino-5-bromo-3-hydroxypyridine (Compound 1013, 24.0 g, 80percent yield) as a tan solid: ESMS (M+H) 189, 191; 1H NMR (DMSO-d6) delta 7.5 (s, IH), 6.9 (s, IH), 5.7 (br, 2H).
With water; sodium hydroxide; for 4h;Reflux; 6-bromo[1 ,3]oxazolo[4,5-o]pyridin-2(3H)-one (I-52) (69 g, 0.3 mol) was added to 10percent aqueous sodium hydroxide (600 ml_) and the mixture was refluxed for 4 h. TLC (EtOAc/hexane= 1 :2) indicated the reaction was complete. The mixture was cooled to room temperature and acidified to pH~7 by dropwise addition of 10percent HCI (300 mL). The precipitate formed was filtered, washed with water (100 mL) and dried undervacuum to afford 2-amino-5-bromopyridin-3-ol (I-53) (58 g, 73percent) as a yellow solid, which was used without further purification.

  • 2
  • [ 39903-01-0 ]
  • [ 65-85-0 ]
  • [ 174469-41-1 ]
YieldReaction ConditionsOperation in experiment
L. 2-Amino-5-bromo-3-pyridinol 6-Bromooxazolo[4,5-b]pyridine-2(3H)-one (K. Rufenacht and H. Kristinsson, Helv. Chim. Acta 59 (5), 1953 [1976]) (4.3 g; 0.02 mole) sodium hydroxide (5 g; 0.125 mole) and water (50 ml) were stirred on the steam bath for 45 minutes. The solution was cooled to approximately 10° C. and carefully acidified with concentrated HCl (considerable foaming). The resulting solid was collected by filtration, washed with water and dried. The yield was 3.0 g (79 percent) of tan solid melting at 187° to 189° C. Recrystallization from aqueous ethanol afforded 2.0 g of tan crystals, melting point 195° to 197° C. Analysis calculated for C5 H5 BrN2 O: C, 37.77; H, 2.67; N, 14.82; Br, 42.27. Found: C, 37.76; H, 2.79; N, 14.87; Br, 41.94.
  • 4
  • [ 1822-32-8 ]
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  • 5
  • [ 619-65-8 ]
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  • 6
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  • [ 130927-83-2 ]
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  • 7
  • [ 39903-01-0 ]
  • [ 339333-00-5 ]
  • [ 364385-39-7 ]
  • 8
  • [ 39903-01-0 ]
  • [ 51052-78-9 ]
  • [ 364385-45-5 ]
  • 9
  • [ 14002-80-3 ]
  • [ 39903-01-0 ]
  • [ 1003023-47-9 ]
YieldReaction ConditionsOperation in experiment
39% With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 120℃; for 0.333333h;Microwave irradiation; To a suspension of <strong>[39903-01-0]2-amino-5-bromopyridin-3-ol</strong> (1.42 g, 7.51 mmol) in THF (40 mL) was added methyl 2,2-dimethyl-3-hydroxypropionate (1.2 mL, 9.0 mmol) and triphenyl phosphine (2.36 g, 9.00 mmol). The mixture was cooled to 0 0C, then treated with diethyl diazodicarboxylate (1.70 g, 9.75 mmol). The mixture was heated in microwave at 120 0C for 20 min. The solvent was concentrated, and the residue was purified by chromatography (silica gel, hexanes/EtOAc, 75:25 to 60:40) to give the title compound (0.88 g, 39percent) as a white solid: 1H NMR (300 MHz, CDCl3) delta 7.73 (d, J= 2.1 Hz, IH), 7.02 (d, J= 2.1 Hz, IH), 4.65 (br s, 2H), 3.96 (s, 2H), 3.71 (s, 3H), 1.34 (s, 6H); ESI MS m/e 303 (M + H)+. b) 3-Bromo-7,7-dimethyl-6,7-dihydro-9H-5-oxa-l,9-diaza-benzocyclohepten-8- one
  • 11
  • [ 39903-01-0 ]
  • [ 364385-32-0 ]
  • 12
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  • 13
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  • [ 364385-34-2 ]
  • 14
  • [ 39903-01-0 ]
  • [ 364385-47-7 ]
  • 15
  • [ 39903-01-0 ]
  • methyl 3-{2-[2-(4-piperidinyl)ethyl]oxazolo[4,5-b]pyridin-6-yl}propanoate [ No CAS ]
  • 16
  • [ 39903-01-0 ]
  • [ 364385-48-8 ]
  • 17
  • [ 39903-01-0 ]
  • methyl 3-(6-amino-5-[3-(4-piperidinyl)propanoyl]oxy}-3-pyridyl)propanoate [ No CAS ]
  • 18
  • [ 39903-01-0 ]
  • methyl (E)-3-{2-[(1-benzyl-4-piperidinyl)methyl]oxazolo[4,5-b]pyridin-6-yl}-2-propenoate [ No CAS ]
  • 19
  • [ 39903-01-0 ]
  • [ 364385-56-8 ]
  • 20
  • [ 39903-01-0 ]
  • [ 364385-49-9 ]
  • 21
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  • [ 364385-42-2 ]
  • 22
  • [ 39903-01-0 ]
  • [ 364385-41-1 ]
  • 23
  • [ 39903-01-0 ]
  • [ 364385-50-2 ]
  • 24
  • [ 39903-01-0 ]
  • [ 364385-57-9 ]
  • 25
  • [ 39903-01-0 ]
  • methyl 3-[2-(4-piperidinylmethyl)oxazolo[4,5-b]pyridin-6-yl]propanoate, formate salt [ No CAS ]
  • 26
  • [ 39903-01-0 ]
  • [ 364385-37-5 ]
 

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