Structure of 2-Chloro-6-fluoroaniline
CAS No.: 363-51-9
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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. : | 363-51-9 |
Formula : | C6H5ClFN |
M.W : | 145.56 |
SMILES Code : | C1=C(C(=C(C=C1)Cl)N)F |
MDL No. : | MFCD00040309 |
InChI Key : | ZJLAWMDJTMMTQB-UHFFFAOYSA-N |
Pubchem ID : | 2734205 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 35.81 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.68 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.49 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.21 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.24 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.68 |
Solubility | 0.305 mg/ml ; 0.0021 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.47 |
Solubility | 0.489 mg/ml ; 0.00336 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.91 |
Solubility | 0.179 mg/ml ; 0.00123 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 |
-5.56 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 |
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) |
1.39 |
* 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 |
---|---|---|
46% | With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 160℃; for 3h;Inert atmosphere; Microwave irradiation; | General procedure: NaOt-Bu (0.240 g, 2.5 mmol), Pd(OAc)2 (0.006 g, 0.025 mmol) and [HPt-Bu3][BF4] (0.010 g, 0.035 mmol) were suspended in toluene (3 ml) in a 5 ml microwave vial. The appropriate 2-chloroaniline (0.50 mmol) and aryl bromide (0.50 mmol) were then added and the vial sealed. The reaction was then heated in the microwave reactor at 160 C for 3 h, allowed to cool, and then quenched by addition of aqueous HCl (2 M, 3 ml). The organic phase was extracted with CH2Cl2 (2×20 ml), dried (MgSO4), then filtered and the solvent removed under reduced pressure. The crude product mixture was then subjected to column chromatography (SiO2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In tetrahydrofuran; at 20℃; for 15h;Inert atmosphere; | To a solution of PE1-028-B2 acid chloride (6.36 g, 0.030 mol) obtained in the previous step in THF (40 mL) under inert conditions, 2-chloro-6-fluoroaniline (4.38 g, 0.03 mol) was addedportion wise and the reaction mixture was stirred at r.t. for 15 h. The resulting precipitate was filtered, washed with DCM (15 mL) and the solid obtained was sonicated in HC1 (1M, 100 mL), filtered and washed with water (20 mL), DCM (20 mL) sequentially and dried under high vacuum to obtain the title compound 7c (5.529 g) as a white solid. The first filtrate (i.e., THF and DCM) was concentrated, slurried with DCM (15 mL) and filtered to get a solid. The solidwas again sonicated with HC1 (1M, 30 mL), filtered and washed with water (20 mL), DCM (15 mL) sequentially and dried under high vacuum to obtain another crop of pure product 7c (1.702 g) also as a white solid. The combined yield of 7c (7.23 1 g, 75%), mp 207-211 C. ‘H NMR (400 MHz, DMSO-d6): ö 10.71 (s, 1H), 9.03 (s, 1H), 7.48-7.36 (m, 3H); ‘9F NMR (376 MHz, DMSOd 6): -115.25, -115.28 (m); LC-MS (ESI+) m/z 319.96 (M+H) HRMS (ESI+) m/z calculated forC,,H6C13FN3O (M+H) 319.9555, found 319.9562. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52.8% | A stirred solution of 9 <strong>[397308-78-0]4-hydroxy-2-methylsulfanyl-pyrimidine-5-carboxylic acid</strong> (5.70 g, 30.65 mmol, 1.0 eq) and 237 2-chloro-6-fluoro-aniline (4.50 g, 30.65 mmol, 1.0 eq) in 24 toluene (200 mL) was purged with nitrogen gas for 15 min. To the above solution 91 PCl3 (30 mL) was added. The reaction was heated at 100 C. for 72 h. Progress of reaction was monitored by LCMS. After completion of reaction, solvent was removed under reduced pressure, residue was diluted with a mixture of 238 diethyl ether: 30 MeOH (10:1) (100 mL) stirred for 15 min then filtered off. Solid was suspended in MeOH (20 mL), stirred for 5 min, filtered off and washed with MeOH (10 mL), and then dried under vacuum to obtain of 239 N-(2-chloro-6-fluoro-phenyl)-4-hydroxy-2-methylsulfanyl-pyrimidine-5-carboxamide (5.0 g, 52.8%). (0370) LCMS: 314 [M+1]+ |