Structure of 740081-22-5
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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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CAS No. : | 740081-22-5 |
Formula : | C17H13ClFN3O3 |
M.W : | 361.75 |
SMILES Code : | CC(OC1=CC2=C(NC3=CC=CC(Cl)=C3F)N=CN=C2C=C1OC)=O |
MDL No. : | MFCD26395271 |
InChI Key : | YJNQYSVKLRFVQN-UHFFFAOYSA-N |
Pubchem ID : | 57476867 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 25 |
Num. arom. heavy atoms | 16 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 92.04 |
TPSA ? Topological Polar Surface Area: Calculated from |
73.34 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.33 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.52 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.67 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.66 |
Solubility | 0.00783 mg/ml ; 0.0000216 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.11 |
Solubility | 0.00283 mg/ml ; 0.00000781 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.95 |
Solubility | 0.0000407 mg/ml ; 0.000000112 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.76 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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.77 |
* 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 |
---|---|---|
100% | With ammonia methyl alcohol; In methanol; at 20℃; for 2h; | Taking compound 3 (200 mg) dissolved in methanol (2 ml) in, adding methanol and ammonia solution (7 N, 1 ml), then stirred at room temperature 2 hours; the reaction the fluid turns on lathe job to the compound 1 (white powder, 176 mg, quant.). |
83% | With ammonia; N,N-diethylaniline; In methanol; at 20℃; for 18h; | To a stirred solution of compound 6 (2.30 g, 5.79 mmol) in MeOH (50 mL) was added concentrated ammonia (4.0 mL). The reaction mixture was stirred at rt for 18 h. The resultant precipitate was filtered, and washed with MeOH to afford 7 (1.54 g, 83%) as a pale yellow solid, mp 280-282 C. 1H NMR (DMSO-d6): d 9.75 (s, 1H), 9.48 (s, 1H), 8.35 (s, 1H), 7.66 (s, 1H), 7.52 (t, J = 6.5 Hz, 1H), 7.45 (t,J = 7.0 Hz, 1H), 7.26 (t, J = 8.0 Hz, 1H), 7.21 (s, 1H), 3.98 (s, 3H). |
81% | With ammonia; In methanol; for 2h;Sealed tube; Inert atmosphere; Heating; | To JGK018 (550 mg, 1.520 mmol) was dropwise added ammonia solution (8.0 mL, 7 N in methanol). After being heated at 50 C (bath temperature) in sealed tube with stirring for 2 h, the reaction mixture was cooled to room temperature and concentrated in vacuo. The resulting white solid were washed successively with Et20 (2 x 50 mL) and collected to give 13 (394 mg, 81%); The resulting spectroscopic data was matched with that of Zhang, X. et al. Med. Chem. 2015, 58, 8200-8215. |
77% | With ammonia; In methanol; water; at 50℃; for 2h; | 6-ACETOXY-4- (3-CHLORO-2-FLUOROANILINO)-7-METHOXYQUINAZOLINE HYDROCHLORIDE FROM step 1 (8.72 g, 21.9 mmol) was dissolved in methanol (200 ml). Concentrated aqueous ammonia (15 ml) was added, and the solution heated to 50C with stirring for 2 hours, causing precipitation of a cream coloured solid. The solid was collected by filtration, washed with diethyl ether (3x 200 ml), and dried in vacuo at 60C over diphosphorous pentoxide, giving the product as an off white solid (5.40 g, 77%); H NMR : 3.95 (s, 3H), 7.19 (s, 1H), 7.23 (dd, 1H), 7.42 (dd, 1H), 7.50 (dd, 1H), 7.64 (s, 1H), 8.32 (s, 1H), 9.43 (s, 1H), 9.67 (br. s, 1H) ; Mass Spectrum: 320.4, 322.4. |
77% | With ammonia; In water; at 50℃; for 2h; | 6-ACETOXY-4- (3-CHLORO-2-FLUOROANILINO)-7-METHOXYQUINAZOLINE hydrochloride from step 1 (8.72 g, 21.9 mmol) was dissolved in methanol (200 ml). Concentrated aqueous ammonia (15 ml) was added, and the solution heated to 50C with stirring for 2 hours, causing precipitation of a cream coloured solid. The solid was collected by filtration, washed with diethyl ether (3x 200 ml), and dried in vacuo at 60C over diphosphorous pentoxide, giving the product as an off white solid (5.40 g, 77%). 1H NMR : 3.95 (s, 3H), 7.19 (s, 1H), 7.23 (dd, 1H), 7.42 (dd, 1H), 7.50 (dd, 1H), 7.64 (s, 1H), 8.32 (s, 1H), 9.43 (s, 1H), 9.67 (br. s, 1H); Mass Spectrum : 320.4, 322.4. |
With methanol; potassium carbonate; at 20℃; | Intermediate 74-[(3-Chloro- -fluorophenyl)aminol-7-methoxyquinazolin-6-olTo a solution of Intermediate 6 (181 g, 0.396 mol) in MeOH (2 L) was added potassium carbonate (138 g, 1 mol) and the reaction mixture was stirred at RT overnight. The reaction mixture was filtered and the solid washed with MeOH. The filtrate was concentrated in vacuo to afford Intermediate 7 (280 g, 60% purity, contained potassium carbonate). 1H NMR (DMSO-d6400MHz): delta 8.01 (s, 1H), 7.61-7.58 (m, 1H), 7.27-7.24 (m, 1H), 7.17-7.13 (m, 1H), 6.95 (s, 1H), 6.83 (s, 1H), 3.79 (s, 3H). | |
With potassium carbonate; In methanol; at 20℃; | To a solution of Intermediate 6 (181 g, 0.396 mol) in MeOH (2 L) was added potassium carbonate (138 g, 1 mol) and the reaction mixture was stirred at RT overnight. The reaction mixture was filtered and the solid washed with MeOH. The filtrate was concentrated in vacuo to afford Intermediate 7 (280 g, 60% purity, contained potassium carbonate). 1H NMR (DMSO-d6 400 MHz): delta 8.01 (s, 1H), 7.61-7.58 (m, 1H), 7.27-7.24 (m, 1H), 7.17-7.13 (m, 1H), 6.95 (s, 1H), 6.83 (s, 1H), 3.79 (s, 3H). | |
30 g | With methanol; ammonium hydroxide; at 20 - 30℃; for 6h; | 35g of compound 4,100g ammonia water,70g of methanol was added to the reaction flask,At a reaction temperature of 20-30 C,Stir for 6h,After TLC detection reaction is complete, suction filtration, and then dried at 40 ~ 50 C, to obtain 30g of compound 5; |
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