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Structure of 1224944-51-7

Chemical Structure| 1224944-51-7

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Product Details of [ 1224944-51-7 ]

CAS No. :1224944-51-7
Formula : C8H6ClN3O2
M.W : 211.61
SMILES Code : O=C(C1=C2N=C(Cl)C=CN2N=C1)OC
MDL No. :MFCD22551533
InChI Key :FDJUGKZMZUVEJD-UHFFFAOYSA-N
Pubchem ID :58063364

Safety of [ 1224944-51-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 1224944-51-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 9
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 49.28
TPSA ?

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

56.49 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.96
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

1.14
Log Po/w (WLOGP)?

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

1.17
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.

1.15
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

0.9
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.26

Water Solubility

Log S (ESOL):?

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

-2.21
Solubility 1.29 mg/ml ; 0.00611 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.

-1.92
Solubility 2.54 mg/ml ; 0.012 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

-2.41
Solubility 0.818 mg/ml ; 0.00386 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

Yes
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.

-6.78 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

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)

1.97

Application In Synthesis of [ 1224944-51-7 ]

* 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 [ 1224944-51-7 ]

[ 1224944-51-7 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 100-82-3 ]
  • [ 1224944-51-7 ]
  • [ 1224939-90-5 ]
YieldReaction ConditionsOperation in experiment
80% With N-ethyl-N,N-diisopropylamine; In ethanol; for 4h;Reflux; Inert atmosphere; A solution of methyl 5-chloropyrazolo[l,5-alpha]pyrimidine-3-carboxylate (240 mg, 1.1 mM, 1.0 equiv), 3-fluorobenzylamine (200 uL, 2.0 mM, 2.0 equiv), 30 mL of ethanol and 400 uL of N,N-diisopropylethylamine (2.0 mM, 2 equiv) were combined and heated under reflux for 4 hours. The mixture was concentrated and the product collected by filtration and washed with cold ethanol to give 271 mg (80%) of methyl 5-(3- fluorobenzylamino)pyrazolo[l,5-alpha]pyrimidine-3-carboxylate LCMS (ESI) m+H = 301.2, 1H NMR (400 MHz, OMSO-d6) delta: 8.56 (d, 1 H), 8.41 (m 1 H), 8.17 (s, 1 H), 7.35 (m, 3 H), 7.08 (td, 1 H), 6.44 (d, 1 H), 4.61 (d, 2 H), 3.74 (s, 3 H).
80% With N-ethyl-N,N-diisopropylamine; In ethanol; for 4h;Reflux; Inert atmosphere; A solution of <strong>[1224944-51-7]methyl 5-chloropyrazolo[1,5-c]pyrimidine-3-carboxylate</strong> (240 mg, 1.1 mM, 1.0 equiv), 3-fluorobenzylamine (200 uL, 2.0 mM, 2.0 equiv), 30 mL of ethanol and 400 uL of N,N-diisopropylethylamine (2.0 mM, 2 equiv) were combined and heated under reflux for 4 hours. The mixture was concentrated and the product collected by filtration and washed with cold ethanol to give 271 mg (80%) of methyl 5-(3-fluorobenzylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylate LCMS (ESI) m+H=301.2, 1H NMR (400 MHz, DMSO-d6) delta: 8.56 (d, 1H), 8.41 (m 1H), 8.17 (s, 1H), 7.35 (m, 3H), 7.08 (td, 1H), 6.44 (d, 1H), 4.61 (d, 2H), 3.74 (s, 3H).
  • 2
  • [ 67-56-1 ]
  • [ 1224944-47-1 ]
  • [ 1224944-51-7 ]
YieldReaction ConditionsOperation in experiment
for 0.5h;Inert atmosphere; A mixture of 5-oxo-4,5-dihydropyrazolo[l,5-alpha]pyrimidine-3-carboxylic acid (151 mg, 0.84 mM, 1.0 equiv), phosphorus oxychloride (20 mL) and N,N- diisopropylethylamine (440 uL, 2.5 mM, 3.0 equiv), were heated under reflux for 2 hours. The reaction mixture was cooled to ambient temperature overnight then concentrated under reduced pressure. The residue was dissolved in 20 mL of methanol, stirred for 30 minutes and concentrated under vacuum. The residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered through a pad of silica gel and concentrated to give 160 mg (90%) of methyl 5-chloropyrazolo[l,5- alpha]pyrimidine-3-carboxylate LCMS (ESI) m+H = 212.2, 1H NMR (400 MHz, DMSO-^) delta: 9.34 (d, 1 H), 8.68 (s, 1 H), 7.42 (d, 1 H), 3.83 (s, 3 H).
  • 3
  • [ 67-56-1 ]
  • [ 1224944-46-0 ]
  • [ 1224944-51-7 ]
YieldReaction ConditionsOperation in experiment
90% A mixture of 5-oxo-4,5-dihydropyrazolo[1,5-c]pyrimidine-3-carboxylic acid (151 mg, 0.84 mM, 1.0 equiv), phosphorus oxychloride (20 mL) and N,N-diisopropylethylamine (440 uL, 2.5 mM, 3.0 equiv), were heated under reflux for 2 hours. The reaction mixture was cooled to ambient temperature overnight then concentrated under reduced pressure. The residue was dissolved in 20 mL of methanol, stirred for 30 minutes and concentrated under vacuum. The residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered through a pad of silica gel and concentrated to give 160 mg (90%) of methyl 5-chloropyrazolo[1,5-c]pyrimidine-3-carboxylate LCMS (ESI) m+H=212.2, 1H NMR (400 MHz, DMSO-d6) delta: 9.34 (d, 1H), 8.68 (s, 1H), 7.42 (d, 1H), 3.83 (s, 3H).
  • 4
  • [ 29274-22-4 ]
  • [ 1224944-51-7 ]
  • 5
  • [ 1224944-44-8 ]
  • [ 1224944-51-7 ]
  • 6
  • [ 1224944-45-9 ]
  • [ 1224944-51-7 ]
  • 7
  • [ 1224944-43-7 ]
  • [ 1224944-51-7 ]
  • 8
  • [ 1224944-51-7 ]
  • [ 365996-30-1 ]
  • methyl 5-[[(1R,2S)-2-(tert-butoxycarbonylamino)cyclohexyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% at 90.0℃; for 0.5h;Sealed tube; Microwave irradiation; A microwave vial was charged with <strong>[1224944-51-7]methyl 5-chloropyrazolo[1,5-a]pyrimidine-3-carboxylate</strong> (500 mg, 2.36 mmol), tert-butyl N-[(1S,2R)-2-aminocyclohexyl]carbamate (506 mg, 2.36 mmol), and methanol (4.7 mL). The vial was sealed and stirred at 90 C for 30 min in the microwave, resulting in a suspension. The reaction mixture was concentrated in vacuo and the crude product was purified by column chromatography (0-100% isopropyl acetate/heptane) to afford methyl 5- [[(1R,2S)-2-(tert-butoxycarbonylamino)cyclohexyl]amino]pyrazolo[1,5-a]pyrimidine-3- carboxylate (420.2 mg, 1.08 mmol, 46% yield) as a white solid. MS: m/z = 390 (M+1).
  • 9
  • [ 1224944-51-7 ]
  • [ 365996-30-1 ]
  • 5-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)amino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [ No CAS ]
  • 10
  • [ 29274-22-4 ]
  • [ 1224944-51-7 ]
  • 11
  • 3-iodopyrazolo[1,5-a]pyrimidine-5-ol [ No CAS ]
  • [ 1224944-51-7 ]
  • 12
  • 5-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylic acid methyl ester [ No CAS ]
  • [ 1224944-51-7 ]
YieldReaction ConditionsOperation in experiment
61.9% With N-ethyl-N,N-diisopropylamine; trichlorophosphate; In toluene; for 2h; 5-hydroxypyrazole [1,5-a] pyrimidine-3-carboxylate (0.028 g, 0.14 mmol)Phosphorus oxychloride (0.8 mL, 8 mmol) andN, N-diisopropylethylamine (0.01 mL, 0.06 mmol)In a toluene (2 mL) solution for 2 h.Cooling to room temperature, removing phosphorus oxychloride under reduced pressure,The residue was quenched with warm water (35 mL), extracted with dichloromethane (35 mL x 3), dried over anhydrous sodium sulfate, concentrated under reduced pressure,Column separation (dichloromethane / methanol (v / v) = 80/1) gave 19 mg of a white solid in 61.9% yield.
  • 13
  • [ 22987-10-6 ]
  • [ 1224944-51-7 ]
  • methyl 5-((3-propionamidophenyl)amino)pyrazolo[1,5-a]pyrimidine-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
15.59% With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 110.0℃; for 6h;Inert atmosphere; N2 protection,The 1,4-dioxane (8 mL) was added to 5-chloro-pyrazolo [1,5-a] pyrimidine-3-carboxylate (0.08g, 0.37mmol),Xantphos (0.011 g, 0.02 mmol),Palladium acetate (4 mg, 0.02 mmol),Cesium carbonate (0.14 g, 0.42 mmol) andN- (3-aminobenzene) propionamide (0.08 g, 0.48 mmol)110 reflux reaction 6h,The filtrate was washed with water (30 mL)The aqueous phase was extracted with dichloromethane (30 mL x 3) and the combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Column separation (dichloromethane / methanol (v / v) = 30/1) gave brown solid,And then subjected to high performance chromatography to give 20 mg of a beige solid in a yield of 15.59%.
 

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Technical Information

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