Structure of 1259224-00-4
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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. : | 1259224-00-4 |
Formula : | C15H22N2O2 |
M.W : | 262.35 |
SMILES Code : | O=C(OC(C)(C)C)NC1(C2=CC=C(N)C=C2)CCC1 |
MDL No. : | MFCD18762015 |
InChI Key : | SOYSJYBVYFILEK-UHFFFAOYSA-N |
Pubchem ID : | 56924485 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.53 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 76.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
64.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.54 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.44 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.07 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.2 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.26 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.5 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.91 |
Solubility | 0.325 mg/ml ; 0.00124 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.43 |
Solubility | 0.0965 mg/ml ; 0.000368 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.09 |
Solubility | 0.0213 mg/ml ; 0.0000813 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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) |
Yes |
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 |
-6.17 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.08 |
* 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 |
---|---|---|
59% | With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 18h;Inert atmosphere; | To a solution of 4-Chloro-5-iodo-pyrimidine (200 mg, 0.83 mmol) and [1- (4-Amino-phenyl)-cyclobutyl]-carbamic acid tert-butyl ester (218 mg, 0.83 mmol) in dioxane (10 mL) was added DIPEA (214 mg, 1.66 mmol). The mixture was heated at 100C for 18 h. After removal of solvent by concentration, the residue was purified by silica gel chromatography eluted with Hexane Ethyl acetate = 10:1 to give { l-[4-(5-Iodo-pyrimidin-4-ylamino)-phenyl]-cyclobutyl}- carbamic acid tert-butyl ester. (230 mg, 59%yield). LCMS (ESI+): 466.8 [M+l]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With triethylamine; In 1,4-dioxane; at 80℃;Inert atmosphere; | To the solution of <strong>[1137576-38-5]4,6-dichloro-5-iodopyrimidine</strong> (5.50 g, 20.00 mmol) (prepared according to the ref of Organic Letters; English; 11; 8; 2009; 1837 - 1840; ) in dioxane (100 mL) was slowly added the solution of tert-butyl l-(4-aminophenyl)cyclobutylcarbamate (5.2 g, 20.00 mmol) in dioxane (20 mL) and Et3N(5 ml). The reaction mixture was stirred at 80C for overnight, lc-ms indicated <strong>[1137576-38-5]4,6-dichloro-5-iodopyrimidine</strong> was completed consumed. After removed the excess solvents under the reduced pressure to get a residue, which was dissolved in Ethyl acetate (250 mL) and washed water and brine. The combined organic layer was dried over Na2S04 and then filtered, the filtrate was concentrated to give the crude product, which was further purified by flash chromatography to afford tert-butyl l-(4-(6-chloro-5-iodopyrimidin-4- ylamino)phenyl)cyclobutylcarbamate. (5.00 g 50% yield).LC/MS: (ESI+): 501 [M+l], 523 [M+Na]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium carbonate; In N,N-dimethyl acetamide; at 100℃; for 18.5h; | 1? (48.0 g, 1.0 equiv.), 2? (59.0 g, 1.1 equiv.), and Na2CO3 (43.4 g, 2.0 equiv.) were charged to a 2 L, 3-neck flask. DMA (310 mL, 6.5 vol.) was added and the reaction was heated to 100 C. After 18.5 hours, HPLC analysis showed the reaction to be complete. The reaction was cooled to 9 C. and 2-MeTHF (960 mL, 20 vol.) was added. 10% aqueous solution of NaCl (720 mL, 15 vol.) was added resulting in some solid formation. The mixture was stirred for one hour and then transferred to a separatory funnel (rinsed the solids forward with 100 mL water). The layers were separated and the aqueous layer (Vaq1200 mL) was back extracted with 2-MeTHF (2×200 mL). The combined organics were then washed with 10% aqueous solution of NaCl (2×250 mL) and then analyzed by 1H NMR for DMA (0.3 wt %). After holding the solution overnight, an aliquot was taken out (6 mL) and was washed (3 mL) with water which resulted in a nice phase split (took >30 minutes). Water (650 mL, batch size) was added and stirred for 10 minutes and then transferred to a separatory funnel and allowed to sit. After 90 minutes, a partial phase split was realized (Vaq=250 mL). Brine (250 mL) was added resulting in a phase split. The organic layer (1300 mL, 27 vol., Kf=3.45%) was split off and charged to a 3-L RB flask. The flask was heated (atmospheric) to distill off some of the 2-MeTHF. Once 15 volumes of 2-MeTHF (720 mL) remained (30 minutes), the solution was reanalyzed for water content (Kf=0.24%). The reaction was then cooled to 50-55 C. and polished filtered through filter paper (very little solids present). The solution was then recharged to the 3-L flask (after cleaning flask) and the solution was distilled down to 9 volumes (430 mL). The solution was then heated to 70 C. and heptane was added in portions over one hour. The heat was then turned off and the solution was allowed to slowly cool to room temperature (after one hour the temperature was 48 C.). After stirring for 70 hours, the mother liquor was checked by HPLC analysis for 3 (2.7 mg/mL) and then filtered. The solids were washed with a 25% 2-MeTHF/heptane solution (75 mL, slurry) followed by 2×240 mL displacement wash with the same solution. The cake was washed one more time with heptane (240 mL) and then dried in a vacuum oven for 20 hours at room temperature. 3 (81.1 g, 86% yield, 99.2% AUC) was isolated as a dark red solid. 1H NMR (CDCl3) analysis showed no residual solvent present. |
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