Structure of 1224944-51-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
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 |
56.49 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.96 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.17 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.21 |
Solubility | 1.29 mg/ml ; 0.00611 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.92 |
Solubility | 2.54 mg/ml ; 0.012 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.41 |
Solubility | 0.818 mg/ml ; 0.00386 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.78 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.97 |
* 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.
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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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