Structure of 69816-35-9
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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. : | 69816-35-9 |
Formula : | C5H4F3N3 |
M.W : | 163.10 |
SMILES Code : | NC1=NC(C(F)(F)F)=CN=C1 |
MDL No. : | MFCD10697803 |
InChI Key : | FMBKXKZEXQCCFM-UHFFFAOYSA-N |
Pubchem ID : | 13341114 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.44 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.8 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.11 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.74 |
Solubility | 2.99 mg/ml ; 0.0183 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.54 |
Solubility | 4.68 mg/ml ; 0.0287 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.17 |
Solubility | 1.1 mg/ml ; 0.00676 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 |
-6.68 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 |
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) |
1.91 |
* 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 |
---|---|---|
With iodine; copper; In chloroform; | (a) 2-Iodo-6-trifluoromethylpyrazine A three liter flask was charged with a solution of <strong>[69816-35-9]2-amino-6-trifluoromethylpyrazine</strong> (obtained by the method of J. L. Miesel, U.S. Pat. No. 4,293,552, 95% pure by HPLC analysis, 32.6 g, 0.20 mol) in chloroform (1000 mL). Freshly ground iodine (101 g. 0.40 mol) was added to give a dark purple solution. After 40 min, a solution of t-butyl nitrite (22.9 g, 0.20 mol) in chloroform (300 mL) was added dropwise over 1 h. During the addition, slow gas evolution was observed together with a mild exotherm (<10 C.) which was moderated with a cold water bath. After an additional 1 h at room temperature the reaction mixture was washed with saturated aqueous sodium sulfite (3*500 mL) to remove the excess iodine. The chloroform solution was dried over magnesium sulphate, filtered and concentrated on a Buchi to give 23 g of an orange oil. The crude product was purified by distillation from copper (40-80 mesh, 200 mg) to give 19.5 g of the title compound as a yellow oil; b.p. 50-56 C./0.6 mmHg; delta (360 MHz, CDCl3) 9.06 (1H, s, pyrazine-H), 8.86 (1H, s, pyrazine-H); m/e 274 (M+). | |
With iodine; In chloroform; | (a) 2-Iodo-6-trifluoromethylpyrazine A three litre flask was charged with a solution of <strong>[69816-35-9]2-amino-6-trifluoromethylpyrazine</strong> (obtained by the method of J.L. Miesel, U.S. Patent 4293552, 95% pure by HPLC analysis, 32.6g, 0.20mol) in chloroform (1000mL). Freshly ground iodine (101g. 0.40mol) was added to give a dark purple solution. After 40 min, a solution of t-butyl nitrite (22.9g, 0.20mol) in chloroform (300mL) was added dropwise over 1h. During the addition, slow gas evolution was observed together with a mild exotherm (< 10C) which was moderated with a cold water bath. After an additional 1h at room temperature the reaction mixture was washed with saturated aqueous sodium sulfite (3 x 500mL) to remove the excess iodine. The chloroform solution was dried over magnesium sulphate, filtered and concentrated on a Buchi to give 23g of an orange oil. The crude product was purified by distillation from copper (40-80 mesh, 200mg) to give 19. 5g of the title compound as a yellow oil; b.p. 50-56C/0.6mmHg; delta (360MHz, CDCl3) 9.06 (1H, s, pyrazine-H), 8.86 (1H, s, pyrazine-H); m/e 274 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; sodium acetate; In methanol; water; | A mixture of 6.6 g. of 3,3-dibromo-1,1,1-trifluoropropanone, 60 ml. of water, and 6.6 g. sodium acetate was refluxed for about 10 minutes. The solution thus obtained was cooled and added dropwise to a solution of 6 g. of aminoacetamidine dihydrobromide in 90 ml. of methanol cooled to a temperature of about -30 C., followed by the addition of a solution of 3.6 g. of sodium hydroxide pellets in 25 ml. of water. The reaction mixture was stirred and warmed gradually to about 20 C. over a period of about two hours. The reaction product mixture was concentrated in vacuo to remove the methanol, and the residue extracted with ethyl acetate. There was obtained product weighing 3.6 g. and having a melting point of about 133-136 C. after recrystallization from a mixture of benzene and hexane. The product was identified by NMR spectrum and elemental analyses as 2-amino-6-trifluoromethylpyrazine. Analyses calcd. for C5 H4 F3 N3: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1-(2-Chlorobenzoyl)-3-(6-trifluoromethyl-2-pyrazinyl)urea, having a melting point of about 179-180 C., from 1.5 g. of <strong>[69816-35-9]2-amino-6-trifluoromethylpyrazine</strong> and 1.6 g. of 2-chlorobenzoylisocyanate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With pyridine; trichlorophosphate; In dichloromethane; at 0 - 20℃; for 2.0h; | To a solution of intermediate 1 (50 mg, 0.306 mmol) in DCM (5 mL) was added 4-(trifluoromethyl)pyrimidin-2-amine (73 mg, 0.306 mmol), pyridine (96.81 mg, 1.224 mmol) followed by POCl3 (51 mg, 0.336 mmol) at 0 C. The mixture was stirred at room temperature for 2 hours before diluted with DCM, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by chromatography on silica gel (PE: EtOAc = 10: 1) to give intermediate 2 (35 mg, yield 82.0%) as colorless oil. LC/MS (ESI) (m/z): 387 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With 1-chloro-1-(dimethylamino)-2-methyl-1-propene; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 16.0h; | Compound 345a was prepared and purified according to the procedure reported in step-1 of scheme-344, from (lR,3S,5R)-2-(tm-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3- carboxylic acid (259a) (177 mg, 0.781 mmol) in DCM (5 mL) using l-chloro-N,N,2- trimethylprop- 1 -en- 1 -amine (0.114 mL, 0.859 mmol), 6-(difhioromethoxy)pyridin-2-amine (125 mg, 0.781 mmol) and DIPEA (202 mg, 1.561 mmol) to afford ( 1R,3 S,5R)-tert-butyl 3- (6-(difluoromethoxy)pyridin-2-ylcarbamoyl)-2-azabicyclo[3.1 ,0]hexane-2-carboxylate (345a) (170 mg, 59% yield) as a pale-yellow solid; NMR (300 MHz, DMSO-cfe) δ 10.44 (s, 1H), 8.04 - 7.85 (m, 2H), 7.57 (s, 1H), 6.88 - 6.64 (m, 1H), 4.34 - 4.05 (m, 1H), 3.35 (s, 1H), 2.38 - 2.21 (m, 1H), 2.21 - 2.02 (m, 1H), 1.71 - 1.53 (m, 1H), 1.32 (s, 9H), 0.84 - 0.64 (m, 1H), 0.50 - 0.33 (m, 1H);19F NMR (282 MHz, DMSO -de) δ -86.36; MS (ES+): 370 (M+l); (ES-): 368 (M-l). |
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