Structure of 67221-50-5
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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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Search for reports by entering the product batch number.
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 67221-50-5 |
Formula : | C4H6N4O |
M.W : | 126.12 |
SMILES Code : | O=C(C1=C(N)C=NN1)N |
MDL No. : | MFCD02646740 |
InChI Key : | JVXDFTZWKFHULK-UHFFFAOYSA-N |
Pubchem ID : | 580973 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 31.09 |
TPSA ? Topological Polar Surface Area: Calculated from |
97.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
-0.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.7 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.9 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.77 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.49 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.82 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.53 |
Solubility | 37.6 mg/ml ; 0.298 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.88 |
Solubility | 16.7 mg/ml ; 0.132 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.42 |
Solubility | 47.5 mg/ml ; 0.377 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 |
No |
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) |
No |
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 |
-7.57 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 |
2.0 |
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) |
1.52 |
* 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 |
---|---|---|
87.2% | With 2,2-dimethyl-N-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-yl)-propionamide; In ethanol; water; for 2.0h; | Intermediate LL (4.0 g, 31.74 mmol) was dissolved by warming in water (200 mL). A mixture of benzoyl isothiocyanate (5.7 g, 34.92 mmol) and ethanol (200 mL) was added slowly to the rapidly stirred solution of compound J. The mixture was stirred for 2 hours, during which time the sides of the flask were frequently scraped clean of adhering solid. At this time, the solid was collected, washed with hot ethanol (50 mL), and dried to yield Intermediate MM as a pale yellow solid (8g, 87.2%). 1H NM (300 MHz, DMSO-<¾): delta 13.68 (s, 1H), 13.3 (s, 1H), 1 1.4 (s, 1H), 9.09 (s, 1H), 7.96 (d, J= 7.5 Hz, 2H), 7.71 (bs, 1H), 7.66-7.63 (m, 1H), 7.55-7.51 (m, 2H), 7.41 (bs, 1H), Mass (M+H): 290 (100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | palladium-on-charcoal; In methanol; at 20.0℃; under 1034.32 Torr; for 2.0h; | To a solution of Intermediate KK (5.0 g, 32.04 mmol) in methanol (95 mL) in a stainless steel Parr hydrogenation flask was added a slurry of 10 % Pd/C (500 mg) in methanol (5 mL). The resulting mixture was shaken at 20 psi at room temperature for a period of 2 hours. The catalyst was filtered over a Celite bed, which was then washed with MeOH. The combined filtrates were evaporated under reduced pressure to yield Intermediate LL (3.0g, 88%), which was used for the next step without further purification. Mass (M+H): 127 (100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In acetic acid; at 180.0℃; for 0.5h;Microwave irradiation; | Stepl: 5 -Phenyl- 1, 6-dihydro-pyrazolo [4, 3-d] pyrimidin-7 -one4-Amino-2H-pyrazole-3-carboxylic acid amide (5mmol) and benzaldehyde (5mmol) were dissolved in acetic acid (14ml) . Subsequently DDQ (3.75mmol) were added and the reaction mixture is heated in the microwave to 180C for 30 minutes. The precipitate was filtered and washed with Et20.Mexact = 212,079Yield 80%HPLC-MS method: ARetention Time : 2.1 minmass found (m+H) : 213.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium t-butanolate; In N,N-dimethyl-formamide; at 100.0℃; for 0.25h;Microwave irradiation; | Method G14: 4-(6-methoxy-2-(pyridin-3-yl)quinazolin-4-ylamino)-1H-pyrazole-5-carboxamide, 2HCl (vi-d):_The method G14 is representative of method G4 and G5 also. This method can be implemented in a similar way except for substitution of the appropriate solvent and adjustment of the temperature) To a microwave vial containing 4-bromo-6-methoxy-2-(pyridin-3-yl)quinazoline (150.0 mg, 0.47 mmol) in DMF (2 mL) was added <strong>[67221-50-5]4-amino-1H-pyrazole-5-carboxamide</strong> (66.0 mg, 0.52 mmol) and sodium tert-butoxide (50 mg, 0.52 mmol). The reaction mixture was heated at 100 C. for 15 mins by microwave irradiation. Water (50 mL) was added to the reaction mixture, and extracted with ethyl acetate (5×50 mL). The crude material was purified via ISCO (silica, 12 g column, 93% CH2Cl2-7% MeOH-0.1% NH4OH) giving the product as a yellow solid. The free base was then converted to the HCl salt to yield the final product as an orange solid (59.8 mg, 0.14 mmol, 22%). LC-MS m/z=362.4 (M+1) (retention time=1.57) 1H NMR (300 MHz, DMSO) delta 11.28 (s, 1H), 9.62 (d, J=1.7 Hz, 1H), 9.17 (d, J=7.8 Hz, 1H), 8.93 (dd, J=5.2, 1.3 Hz, 1H), 8.60 (s, 1H), 8.05 (s, 1H), 8.03-7.94 (m, 2H), 7.77 (s, 1H), 7.64 (dd, J=9.2, 2.5 Hz 1H), 7.40 (d, J=2.6 Hz, 1H), 3.97 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With sodium t-butanolate; In N,N-dimethyl-formamide; at 100.0℃; for 0.25h;Microwave irradiation; | A DMF solution (2 mL) of 4-bromo-6-methoxy-2- (pyridin-3-yl) quinazoline (150.0 mg, 0.47 mmol)Was placed 4-amino-1 H-pyrazole-5-carboxamide (66.0 mg, 0.52 mmol) and sodium tert-butoxide (50 mg, 0.52 mmol).The reaction mixture was heated by microwave irradiation at 100 C. for 15 minutes.Water (50 mL) was added to the reaction mixture and extracted with ethyl acetate (5 × 50 mL).The crude product was purified by ISCO (silica, 12 g column, 93% CH 2 Cl 2 - 7% MeOH - 0.1% NH 4 OH) to give the product as a yellow solid.The free base was then converted to the HCl salt and the final product was obtained as an orange solid (59.8 mg, 0.14 mmol, 22%). |