Structure of 1001020-17-2
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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. : | 1001020-17-2 |
Formula : | C8H12N2O |
M.W : | 152.19 |
SMILES Code : | O=CC1=CNN=C1C(C)(C)C |
MDL No. : | MFCD07186448 |
InChI Key : | JQCJTNPAWAQSFC-UHFFFAOYSA-N |
Pubchem ID : | 3159701 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.12 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.39 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.52 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.44 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.86 |
Solubility | 2.08 mg/ml ; 0.0137 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.95 |
Solubility | 1.69 mg/ml ; 0.0111 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.38 |
Solubility | 0.639 mg/ml ; 0.0042 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 |
-6.24 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) |
1.7 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | b) 3-Te/t-butyM /-/-pyrazole-4-carbaldehydePhosphorus oxychloride (18.2 ml_, 195 mmol) was added portionwise to DMF (30 ml_, 387 mmol) at < 5 0C. Pinacolone semicarbazone (15.4 g, 97.6 mmol) was added over 1 h maintaing the temperature at < 5 0C. The reaction mixture became very thick so an additional quantity of DMF (10 mL) was added. The mixture was heated to 60 0C for 3.5 h then allowed to cool and poured into ice. The reaction was neutralised using sodium hydroxide (40 g, 1 mol) in water (130 mL) then heated at 60 0C for 5 min. The mixture was <n="66"/>cooled in an ice bath and acidified to pH 6 and the product extracted into EtOAc. The EtOAc was dried over MgSO4 and concentrated onto silica. The crude product was purified by flash chromatography using elutants EtOAc/heptane. Trituration in diethyl ether gave a white solid (1.02 g, 6.1 mmol, 6 %). 1 H NMR (400MHz, CDCI3): delta 1.48 (s, 9H), delta 8.07 (s, 1 H)1 delta 10.06 (s, 1 H) delta 10.25 (b, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 3h; | Example 78 2-(2-(3-7erf-butyl-4-formyl-1H-pyrazol-1-vnacetan?ido)-N-nnethyl-4,5.6,7- tetrahvdrobenzofblthiophene-3-carboxannide3-Terf-butyl-1H-pyrazole-4-carbaldehyde (150 mg, 0.986 mmol), 2-(2-bromoacetamido)- N-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxannide (490 mg, 1.478 mmol) and potassium carbonate (545 mg, 3.94 mmol) were mixed with DMF (5 ml_) and heated for 3 h at 60 0C. The reaction was partitioned between water and EtOAc. Organics were combined and purified by chromatography (0-60%, EtOAc/heptane) to give the title product as a white solid (360 mg, 0.894 mmol, 91 %). MS (ESI): m/z 403.6 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Example 842-(2-(3-rert-butyl-4-formyl-1H-pyrazol-1-vhacetamido)-N-(2-hvdroxyethvn-4.5.6.7- tetrahvdrobenzofbithiophene-3-carboxamide <n="78"/>2-(2-Bromoacetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxamide (1.66 g, 4.60 mmol), 3-tert-butyl-1 H-pyrazole-4-carbaldehyde (1.75 g, 11.49 mmol) and potassium carbonate (2.54 g, 18.38 mmol) were mixed with DMF (20 ml_) and heated at 70 CC for 2 h. On cooling, the reaction was partitioned between EtOAc and water. The organics were washed with brine, dried over MgSO4 and concentrated directly onto silica for chromatographic purification (0-100 % EtOAc/heptane). Concentration in vacuo yielded a white solid (1.64 g, 3.79 mmol, 83 %). MS (ESI): m/z 433.5 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 3h; | A mixture of A-i (750 mg, 4.93 mmol), A-2 (0.46 mL, 7.39 mmol) and K2C03 (2.72 g, 19.71 mmol) in 10 mL DMF is heated at 85 C for 3 hours. The reaction mixture is diluted with EtOAc, washed with water, brine, dried over Na2SO4, concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with 10-100% EtOAc in heptane to yield Intermediates A and B as a 10:1 mixture by 1HNMR. |
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