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Structure of 882562-39-2

Chemical Structure| 882562-39-2

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Product Details of [ 882562-39-2 ]

CAS No. :882562-39-2
Formula : C14H13BN2O4S
M.W : 316.14
SMILES Code : [S](=O)(=O)(C1=CC=C(C)C=C1)[N]3C2=NC=CC=C2C(=C3)B(O)O
MDL No. :MFCD10696634
InChI Key :ZJMVMHYCONCGCX-UHFFFAOYSA-N
Pubchem ID :45789698

Safety of [ 882562-39-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 882562-39-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 22
Num. arom. heavy atoms 15
Fraction Csp3 0.07
Num. rotatable bonds 3
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 83.59
TPSA ?

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

100.8 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

1.76
Log Po/w (WLOGP)?

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

1.34
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.

1.44
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

-0.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.74

Water Solubility

Log S (ESOL):?

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

-3.22
Solubility 0.193 mg/ml ; 0.000609 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.

-3.49
Solubility 0.101 mg/ml ; 0.00032 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

-3.79
Solubility 0.0516 mg/ml ; 0.000163 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.

-6.98 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)

3.04

Application In Synthesis of [ 882562-39-2 ]

* 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 [ 882562-39-2 ]

[ 882562-39-2 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 5419-55-6 ]
  • [ 226085-18-3 ]
  • [ 882562-39-2 ]
YieldReaction ConditionsOperation in experiment
69.4% With n-butyllithium In tetrahydrofuran at -90 - -80℃; for 0.5 h; Large scale [0387] Example lc: l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-ylboronic acid (8a) [0388] THF (28.5 kg) and 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine (7a) (4 kg) were added to a 72 L flask. The mixture was stirred until the solid dissolved completely. Triisopropyl borate (3.2 kg) was added and the mixture was cooled to below -80 °C. n-BuLi (4.65 kg) was added drop wise at a rate of about 0.6-0.9 kg/hour maintaining the temperature of about -80 to -90 °C. After the addition, the temperature was maintained at -80 to -90 °C. The completeness of the reaction was measured by HPLC (method A) with sample aliquots after 30 minutes. The reaction was considered complete when the peak area of 3-bromo-l- tosyl-lH-pyrrolo[2,3-b]pyridine (7a) was less than 4percent. [0389] Water (2 kg) was slowly added to the mixture to quench the reaction. The mixture temperature returned to about 15-25 °C. The mixture was transferred to a 50 L reactor to be concentrated below 40 °C under vacuum of a pressure less than -0.08 MPa until no THF distilled out. The residue was dissolved into water (25 kg) and 10percent aqueous NaOH solution (26 kg). The mixture was stirred until the solid dissolved completely. The mixture was transferred into a vacuum filter and filtered. The filtrate was extracted twice with MTBE (21 kg each) at about 20-30 °C. During each extraction, the mixture was stirred 15 minutes and held 15 minutes. HC1 (28L) was added into the aqueous phase to adjust the pH to between 3 and 4 while maintaining the temperature of about 10-20 °C. The mixture was stirred at about 10-15 °C for 1 hour. The mixture was transferred into a centrifuge and filtered. The resultant cake after filtering was washed with water (5 kg) and petroleum ether (5 kg). The cake was dried at 35-45 °C until the LOD (loss on drying) was less than 3percent. An off-white solid resulted (2.5 kg and 98.8percent purity as measured by HPLC analysis (method A), 69.4percent yield of l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-ylboronic acid (8a)).
69.4% With n-butyllithium In tetrahydrofuran at -90 - -80℃; Large scale [00390] 1 -tosyl-1 H-pyrrolo[2,3-b]pyridin-3-ylboronic acid: [00391] THF (28.5 kg) and 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine (4 kg) were added to a 72L flask. The mixture was stirred until the solid dissolved completely. Triisopropyl borate (3.2 kg) was added and the mixture was cooled to below -80 °C. n-BuLi (4.65 kg) was added drop wise at a rate of about 0.6-0.9 kg/hour maintaining the temperature of about -80 to -90 °C. After the addition, the temperature was maintained at about -80 to -90 °C. The completeness of the reaction was measured by HPLC (method A) with sample aliquots after 30 minutes. The reaction was considered complete when the peak area of 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine was less than 4percent. Typical retention time for 1 -tosyl-1 H-pyrrolo[2,3-b]pyridin-3-ylboronic acid was 4.6 minutes. Extra triisopropyl borate and n-BuLi was added to lower the peak area of 3 -bromo-1 -tosyl-1 H-pyrrolo [2,3 -b]pyridine. [00392] Water (2 kg) was slowly added to the mixture to quench the reaction. The mixture temperature returned to about 15-25 °C. The mixture was transferred to a 50L reactor to be concentrated below 40 °C under vacuum of a pressure less than -0.08 MPa until no THF distilled out. The residue was dissolved into water (25 kg) and 10percent aqueous NaOH solution (26 kg). The mixture was stirred until the solid dissolved completely. The mixture was transferred into a vacuum filter and filtered. The filtrate was extracted twice with MTBE (21 kg each) at about 20-30 °C. During each extraction, the mixture was stirred 15 minutes and held 15 minutes. HC1 acid (28L) was added into the aqueous phase to adjust the pH to between 3 and 4 while maintaining the temperature of about 10-20 °C. The mixture was stirred at about 10-15 °C for 1 hour. The mixture was transferred into a centrifuge and filtered. The resultant cake after filtering was washed with water (5 kg) and petroleum ether (5 kg). The cake was dried at 35-45 °C until the LOD (loss on drying) was less than 3percent. An off-white solid resulted (2.5 kg and 98.8percent purity as measured by HPLC analysis (method A), 69.4percent yield of l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-ylboronic acid).
69.4%
Stage #1: With n-butyllithium In tetrahydrofuran at -90 - -80℃; Large scale
Stage #2: With water; sodium hydroxide In tetrahydrofuranLarge scale
[0275] l-tosyl-lH-pyrrolo[2, 3-b ]pyridin-3-ylboronic acid: [0276] THF (28.5 kg) and 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine (4 kg) were added to a 72L flask. The mixture was stirred until the solid dissolved completely. Triisopropyl borate (3.2 kg) was added and the mixture was cooled to below -80 °C. n-BuLi (4.65 kg) was added drop wise at a rate of about 0.6-0.9 kg/hour maintaining the temperature of about -80 to -90 °C. After the addition, the temperature was maintained at about -80 to -90 °C. The completeness of the reaction was measured by HPLC (method A) with sample aliquots after 30 minutes. The reaction was considered complete when the peak area of 3-bromo-l-tosyl- lH-pyrrolo[2,3-b]pyridine was less than 4percent. Typical retention time for 1-tosyl-lH- pyrrolo[2,3-b]pyridin-3-ylboronic acid was 4.6 minutes. Extra triisopropyl borate and n-BuLi was added to lower the peak area of 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine. [0277] Water (2 kg) was slowly added to the mixture to quench the reaction. The mixture temperature returned to about 15-25 °C. The mixture was transferred to a 50L reactor to be concentrated below 40 °C under vacuum of a pressure less than -0.08 MPa until no THF distilled out. The residue was dissolved into water (25 kg) and 10percent aqueous NaOH solution (26 kg). The mixture was stirred until the solid dissolved completely. The mixture was transferred into a vacuum filter and filtered. The filtrate was extracted twice with MTBE (21 kg each) at about 20-30 °C. During each extraction, the mixture was stirred 15 minutes and held 15 minutes. HC1 acid (28L) was added into the aqueous phase to adjust the pH to between 3 and 4 while maintaining the temperature of about 10-20 °C. The mixture was stirred at about 10-15 °C for 1 hour. The mixture was transferred into a centrifuge and filtered. The resultant cake after filtering was washed with water (5 kg) and petroleum ether (5 kg). The cake was dried at 35-45 °C until the LOD (loss on drying) was less than 3percent. An off-white solid resulted (2.5 kg and 98.8percent purity as measured by HPLC analysis (method A), 69.4percent yield of l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-ylboronic acid).
References: [1] Patent: WO2013/6634, 2013, A2, . Location in patent: Paragraph 0387-0389.
[2] Patent: WO2013/70606, 2013, A1, . Location in patent: Paragraph 00390-00392.
[3] Patent: WO2014/74471, 2014, A1, . Location in patent: Paragraph 0275-0277.
  • 2
  • [ 226085-18-3 ]
  • [ 882562-39-2 ]
YieldReaction ConditionsOperation in experiment
69.4% With n-butyllithium; Triisopropyl borate In tetrahydrofuran at -90 - -80℃; Large scale [0397] 1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-ylboronic acid: [0398] THF (28.5 kg) and 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine (4 kg) were added to a 72L flask. The mixture was stirred until the solid dissolved completely. Triisopropyl borate (3.2 kg) was added and the mixture was cooled to below -80 °C. n-BuLi (4.65 kg) was added drop wise at a rate of about 0.6-0.9 kg/hour maintaining the temperature of about -80 to -90 °C. After the addition, the temperature was maintained at about -80 to -90 °C. The completeness of the reaction was measured by HPLC (method A) with sample aliquots after 30 minutes. The reaction was considered complete when the peak area of 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine was less than 4percent. Typical retention time for l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-ylboronic acid was 4.6 minutes. Extra triisopropyl borate and n-BuLi was added to lower the peak area of 3-bromo-l-tosyl-lH-pyrrolo[2,3-b]pyridine. [0399] Water (2 kg) was slowly added to the mixture to quench the reaction. The mixture temperature returned to about 15-25 °C. The mixture was transferred to a 50 L reactor to be concentrated below 40 °C under vacuum of a pressure less than -0.08 MPa until no THF distilled out. The residue was dissolved into water (25 kg) and 10percent aqueous NaOH solution (26 kg). The mixture was stirred until the solid dissolved completely. The mixture was transferred into a vacuum filter and filtered. The filtrate was extracted twice with MTBE (21 kg each) at about 20-30 °C. During each extraction, the mixture was stirred 15 minutes and held 15 minutes. HC1 acid (28L) was added into the aqueous phase to adjust the pH to between 3 and 4 while maintaining the temperature of about 10-20 °C. The mixture was stirred at about 10-15 °C for 1 hour. The mixture was transferred into a centrifuge and filtered. The resultant cake after filtering was washed with water (5 kg) and petroleum ether (5 kg). The cake was dried at 35-45 °C until the LOD (loss on drying) was less than 3percent. An off-white solid resulted (2.5 kg and 98.8percent purity as measured by HPLC analysis (method A), 69.4percent yield of l-tosyl-lH-pyrrolo[2,3-b]pyridin-3-ylboronic acid).
References: [1] Patent: WO2014/201332, 2014, A1, . Location in patent: Paragraph 0397-0399.
  • 3
  • [ 664982-01-8 ]
  • [ 882562-39-2 ]
YieldReaction ConditionsOperation in experiment
22%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.5 h;
Stage #2: With Triisopropyl borate In tetrahydrofuran at -78℃; for 1 h;
To a solution of 3-iodo-l-[(4-methylphenyl)sulfonyl]-lH-pyrrolo[2,3-δ]pyridine (CAS 664982-01-8) (2.0 g) in anhydrous THF (40 ml) at -78°C under nitrogen was added n-BuLi (2.5M in hexane, 3.0 ml). The mixture was stirred for 30 min at -78°C and triisopropyl borate (1.75 ml) was added. The mixture was stirred at -78°C for 1 hour, quenched with 2N HCl (10 ml) and allowed to warm to room temperature. The pH of the mixture was adjusted to pH 6-7 with IN NaOH solution, saturated with NaCl and extracted with EtOAc (2 x 100 ml). The combined organic layers were dried over Na2SO4, filtered and the solvent removed in vacuo. Trituration of the residue in Et2O yielded the title compound as a yellow solid (350 mg, 22percent). LCMS 317.1 [M+H]+, RT 2.97 min. 1H NMR 300 MHz (d6-DMSO) 8.40 (1H, s), 8.35-8.30 (1H, m), 8.25 (1H, d), 8.00 (2H, d), 7.45 (2H, d), 7.25 (1H, q), 2.35 (3H, s).
References: [1] Patent: WO2006/38001, 2006, A1, . Location in patent: Page/Page column 39.
  • 4
  • [ 7732-18-5 ]
  • [ 73183-34-3 ]
  • [ 226085-18-3 ]
  • [ 866545-91-7 ]
  • [ 882562-39-2 ]
References: [1] Patent: US2018/179199, 2018, A1, . Location in patent: Paragraph 0449-0450.
  • 5
  • [ 271-63-6 ]
  • [ 882562-39-2 ]
References: [1] Patent: WO2013/6634, 2013, A2, .
[2] Patent: WO2013/70606, 2013, A1, .
[3] Patent: WO2014/74471, 2014, A1, .
[4] Patent: WO2014/201332, 2014, A1, .
  • 6
  • [ 74420-15-8 ]
  • [ 882562-39-2 ]
References: [1] Patent: WO2013/6634, 2013, A2, .
[2] Patent: WO2013/70606, 2013, A1, .
[3] Patent: WO2014/74471, 2014, A1, .
[4] Patent: WO2014/201332, 2014, A1, .
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 882562-39-2 ]

Organoborons

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Related Parent Nucleus of
[ 882562-39-2 ]

Other Aromatic Heterocycles

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