Structure of 111600-83-0
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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. : | 111600-83-0 |
Formula : | C4H4BrNS |
M.W : | 178.05 |
SMILES Code : | CC1=C(Br)SC=N1 |
MDL No. : | MFCD12026322 |
InChI Key : | IIMLZWMRQNCPTM-UHFFFAOYSA-N |
Pubchem ID : | 15020997 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 34.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.13 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.38 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.21 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.92 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.3 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.13 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.97 |
Solubility | 0.19 mg/ml ; 0.00107 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.88 |
Solubility | 0.232 mg/ml ; 0.0013 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.53 |
Solubility | 0.524 mg/ml ; 0.00294 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 |
-5.7 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) |
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 |
---|---|---|
82% | With potassium carbonate; | Step 4 To a solution of tert-butyl N-tert-butoxycarbonyl-N-[[2-cyano-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl]carbamate (2.2 g, 4.80 mmol, 1 eq), 5-bromo-4-methyl-thiazole (940 mg, 5.28 mmol, 1.1 eq) in dioxane (20 mL) and water (4 mL) was added potassium carbonate (1.66 g, 12.00 mmol, 2.5 eq) and <strong>[72287-26-4](1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride</strong> (351 mg, 0.48 mmol, 0.1 eq) under nitrogen. The reaction mixture was stirred at 100 C. for 12 hours. Water (100 mL) was added to the mixture, the resulting mixture was extracted with ethyl acetate (50 mL*3). The combined organic phase was washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=100:1 to 1:1). tert-Butyl N-tert-butoxycarbonyl-N-[[2-cyano-4-(4-methylthiazol-5-yl)phenyl]methyl]carbamate (1.7 g, 3.96 mmol, 82% yield) was obtained as a light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate; | Step 5 To a solution of 5-bromo-4-methyl-thiazole (800 mg, 4.49 mmol, 1 eq) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.37 g, 5.39 mmol, 1.2 eq) in dioxane (10 mL) was added 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (164 mg, 0.22 mmol, 0.05 eq) and potassium acetate (882 mg, 8.99 mmol, 2 eq). The reaction mixture was stirred at 100 C. for 12 h. The reaction mixture was filtered and concentrated under reduced pressure to give 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (1 g, crude) as a brown oil which was used without purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 90℃; for 2h;Inert atmosphere; | To a solution of 5-bromo-4-methyl-1,3-thiazole (1.9 g, 10.7 mmol) in dioxane (19 mL) were added H2O (1.9 mL), <strong>[489446-42-6][4-([[(tert-butoxy)carbonyl]amino]methyl)phenyl]boronic acid</strong> (4.0 g, 16.0 mmol), Na2CO3 (2.3 g, 21.3 mmol) and Pd(dppf)Cl2·CH2Cl2 (871.4 mg, 1.1 mmol). The mixture was purged with N2 for 3 times and was stirred at 90 oC for 2 hours under N2 atmosphere. The resulting mixture was cooled to room temperature, diluted with water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layers was washed with brine (2 x 30 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with petroleum ether in ethyl acetate (v/v = 1/1) to afford tert-butyl N-[[4-(4-methyl-1,3-thiazol- 5-yl)phenyl]methyl]carbamate (3 g, 91%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) d 8.98 (s, 1H), 7.53-7.42 (m, 3H), 7.33 (d, J = 8.0 Hz, 2H), 4.16 (d, J = 6.2 Hz, 2H), 2.45 (s, 3H), 1.40 (s, 9H). LC/MS (ESI, m/z): [(M + 1)]+ = 305.2 |
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