Structure of 187973-60-0
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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. : | 187973-60-0 |
Formula : | C4H4IN3 |
M.W : | 221.00 |
SMILES Code : | NC1=NN=C(I)C=C1 |
MDL No. : | MFCD09991754 |
InChI Key : | QHEUBRHRIJMZOR-UHFFFAOYSA-N |
Pubchem ID : | 10867834 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 39.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.8 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.21 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.67 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.74 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.31 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.82 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.88 |
Solubility | 2.92 mg/ml ; 0.0132 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.83 |
Solubility | 33.0 mg/ml ; 0.149 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.25 |
Solubility | 1.24 mg/ml ; 0.00561 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) |
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 |
-7.52 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 |
1.0 |
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 |
1.0 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) |
2.28 |
* 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 |
---|---|---|
81% | In N,N-dimethyl acetamide; water; | Reference Example 3 Production of ethyl (6-iodoimidazo[1,2-b]pyridazin-2-yl)carbamate To a solution of 3-amino-6-iodopyridazine (27.0 g, 122 mmol) in N,N-dimethylacetamide (270 mL) were added <strong>[6092-47-3]ethyl (chloroacetyl)carbamate</strong> (32.4 g, 195 mmol) and disodium hydrogenphosphate (43.4 g, 305 mmol), and the mixture was stirred at 110 C. for 3 hr. After cooling the mixture to room temperature, water (810 mL) was added, and the precipitated crystals were filtrated, and washed with acetonitrile and ether to give the title compound (33.0 g, 81%) as a dark brown powder. 1H-NMR (DMSO-d6, 300 MHz) δ 1.26 (3H, t, J=7.1 Hz), 4.17 (2H, q, J=7.1 Hz), 7.47 (1H, d, J=9.2 Hz), 7.70 (1H, d, J=9.2 Hz), 8.06 (1H, s), 10.51 (1H, brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With disodium hydrogenphosphate; In N,N-dimethyl acetamide; at 110℃; for 3h; | To a stirred solution of 3-amino-6-iodopyridazine (5)30 (27.0 g, 122 mmol) in DMA (270 mL) were added <strong>[6092-47-3]ethyl (chloroacetyl)carbamate</strong> (32.4 g, 196 mmol) and Na2HPO4 (43.4 g, 306 mmol), and the mixture was stirred at 110 C for 3 h. After cooling to room temperature, the mixture was diluted with water (810 mL), and the precipitate was collected by filtration and washed with CH3CN followed by Et2O to give 6 (33.0 g, 81%) as a dark brown solid. 1H NMR (300 MHz, DMSO-d6) δ 1.26 (3H, t, J = 7.1 Hz), 4.17 (2H, q, J = 7.1 Hz), 7.47 (1H, d, J = 9.2 Hz), 7.70 (1H, d, J = 9.2 Hz), 8.06 (1H, s), 10.51 (1H, br s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16%; 18% | Toa mixture of 6-iodopyridazin-3-amine (500 mg, 2.26 mmol), NaHC03(230 mg, 2.71 mmol) in MeOH (5 mL) was added bromine (117 μ, 2.26 mmol)dropwise. The resulting mixture was stirred at room temperature for 16 hrs. Thesolution was filtered and the filtrate concentrated in vacuo. The residue wasdissolved in water, and the product extracted with EtOAc (3 times). The organiclayers were combined, dried ( a2S04) and concentrated invacuo to give a dark red solid which was purified by flash silicachromatography (eluent: 20% EtOAc :Hexane) to give a 60:40 mixture of the titlecompounds as an off white solid (250 mg); H NMR (400 MHz, CDC13) δ5.49 (s, 4H), 7.66 (s, 1H), 7.81 (s, 1H)Toa stirred solution of a mixture of 4,6-dibromopyridazin-3-amine and 4-bromo-6-iodopyridazin-3-amine (10 g, compounds not separated in previous step,estimated 34 mmol) in methanol (90 mL) was added solid sodium methoxide (3.6 g,67 mmol) at room temperature and the reaction mixture stirred at 90C for16hrs. More sodium methoxide was added regularly until all starting materialhad been consumed. The cooled solution was concentrated in vacuo and theresidue poured into water (200 mL). The resulting solution was extracted withEtOAc three times and the organic layers were combined, dried (MgSC^), andconcentrated in vacuo. The residue was purified by silica column chromatography(eluent: chloroform: methanol (98:0.2 to 90:10) to afford the title mixture ofmethoxy ethers (3.0g, taken into next steps without further purification); HNMR (400 MHz, CDC13) δ 3.90 (s, 3H), 3.92 (s, 3H), 5.05 (m, 3H),6.75 (s, 1H), 6.91 (s, 1H).To a stirred solution of (6-bromo-4-methoxypyridazin-3-amine and 6-iodo-4-methoxy- pyridazin-3 -amine (0.8 g, mixture not separated in previous step, estimated 3.92 mmol) in pyridine (9 mL) was added <strong>[163295-70-3](3,5-dichlorophenyl)methanesulfonyl chloride</strong> (1.02 g, 3.92 mmol) at room temperature and the mixture stirred for 16 hrs. Water was then added and the mixture extracted with EtOAc (3x 150 mL). The combined organic layers were washed with more water and brine, then concentrated and purified by flash silica chromatography (eluent: 1% MeOH:DCM) to afford a mixture of methoxy ethers (250mg). To this mixture in DCM (5 mL) was added neat boron tribromide (166 μ, 1.76 mmol) and the mixture stirred for 3h before being diluted with DCM and neutralised with saturated NaHC03 (pH 7). The phases were separated and the aqueous phase extracted with DCM and EtOAc. The combined organic layers were dried (MgSC^), the mixture filtered and the filtrate concentrated to dryness to yield an oil which was purified by automated reverse phase HPLC (low pH method) to afford 1 -(3,5-dichlorophenyl)-N-(4- hydroxy-6-iodopyridazin-3-yl)methanesulfonamide (22 mg, 16%) and -(6-bromo-4- hydroxypyridazin-3-yl)-l-(3,5)-dichlorophenyl)methanesulfonamide (22 mg, 18%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; sodium hydrogencarbonate; In methanol; at 20℃; for 16.0h; | Toa mixture of 6-iodopyridazin-3-amine (500 mg, 2.26 mmol), NaHC03(230 mg, 2.71 mmol) in MeOH (5 mL) was added bromine (117 mu, 2.26 mmol)dropwise. The resulting mixture was stirred at room temperature for 16 hrs. Thesolution was filtered and the filtrate concentrated in vacuo. The residue wasdissolved in water, and the product extracted with EtOAc (3 times). The organiclayers were combined, dried ( a2S04) and concentrated invacuo to give a dark red solid which was purified by flash silicachromatography (eluent: 20% EtOAc :Hexane) to give a 60:40 mixture of the titlecompounds as an off white solid (250 mg); H NMR (400 MHz, CDC13) delta5.49 (s, 4H), 7.66 (s, 1H), 7.81 (s, 1H) |