Structure of 147539-41-1
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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. : | 147539-41-1 |
Formula : | C11H22N2O2 |
M.W : | 214.30 |
SMILES Code : | O=C(N1CCC(NC)CC1)OC(C)(C)C |
MDL No. : | MFCD02259411 |
InChI Key : | CZYUGTLMFHDODF-UHFFFAOYSA-N |
Pubchem ID : | 15380702 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.91 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 64.2 |
TPSA ? Topological Polar Surface Area: Calculated from |
41.57 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.87 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.24 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.22 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.45 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.69 |
Solubility | 4.42 mg/ml ; 0.0206 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.71 |
Solubility | 4.17 mg/ml ; 0.0195 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.72 |
Solubility | 4.08 mg/ml ; 0.0191 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 |
-6.73 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 |
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) |
2.24 |
* 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 potassium acetate; In acetonitrile;Heating / reflux; | 152 (l-r2-(lH-Indazol-4-ylV4-morpholin-4-yl-thienor3.2-d1pyrimidin-6-ylmethyl1- piperidin-4-vU-(3-methanesulfonyl-propylVmethyl-amine.Via [ 1 -(2-chloro-4-morpholin-4-yl-thieno[3 ,2-d]pyrimidin-6-ylmethyl)- piperidin-4-yl]-(3-methanesulfonyl-propyl)-methyl-amine, prepared from (3- methanesulfonyl-propyl)-methyl-piperidin-4-yl-amine. Amine preparation: Toluene-4-sulfonic acid 3-methylsulfanyl-propyl ester was prepared from 3-(methylthio)-l-propanol using standard conditions. Treatment with mCPBA in DCM yielded <strong>[263400-88-0]toluene-4-sulfonic acid 3-methanesulfonyl-propyl ester</strong>. A mixture of 4-methylamino-piperidine- 1-carboxylic acid tert-butyl ester and <strong>[263400-88-0]toluene-4-sulfonic acid 3-methanesulfonyl-propyl ester</strong> was heated in MeCN in the prescence of potassium carbonate to yield 4- [(3-methanesulfonyl-propyl) -methyl- EPO <DP n="82"/>amino]-piperidine-l-carboxylic acid tert-butyl ester. Treatment of this compound with HCl in DCM/MeOH yielded the desired amine, isolated as the hydrochloride salt.1H NMR (400MHz, CDCl3) 1.50-1.70 (m, 4H, 2 x CH2), 1.90-1.97 (m, 2H, CH2), 2.00-2.05 (m, 2H, CH2), 2.21 (s, 3H, CH3), 2.38 (m, H, CH), 2.55 (m, 2H, CH2), 2.74 (s, 3H, CH2), 2.96-3.04 (m, 4H, 2 x CH2), 3.75 (s, 2H, CH2), 3.83-3.89 (m, 4H, 2 x CH2), 4.00-4.02 (m, 4H, 2 x CH2), 7.28 (s, H, CH), 7.41 (t, H, ArH, J=7.74Hz), 7.50 (d, H, ArH, J=8.24Hz), 8.18 (d, H, ArH, J=7.05Hz), 8.93 (s, H, ArH); MS (ESI+) 584.39 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; | Reference Example 5 By allowing benzyl 4-(methylamino)piperidine-1-carboxylate to react with EDCI hydrochloride, HOBt and 1-methyl-L-proline, tert-butyl 4-[methyl(1-methyl-L-prolyl)amino]piperidine-1-carboxylate was obtained. Then, trifluoroacetic acid was added thereto to obtain N,1-dimethyl-N-piperidin-4-yl-L-prolinamide. ES: 226. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 65℃; for 30h; | Step 1HCJNIG base (28.03 g, 0.217 mol) is added to the solution of 6-chloro-3-nitro-2- methylpyridine SM-3 (25 g, 145 mmol) and 4-methylamino-piperdine-1-carboxylic acid- te/f-butylester SM-5a (40.36 g, 188 mmol) in dry AcCN (200 mL) and stirred for 30 h at 65 °C. After the reaction is finished the reaction mixture is diluted with AcCN and water and stirred for 15 min. The precipitated product is collected by filtration, washed with water and the solid is dried in vacuo. | |
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 65℃; for 30h; | HUeNIG base (28.03 g, 0.217 mol) is added to the solution of <strong>[22280-60-0]6-chloro-3-nitro-2-methylpyridine</strong> SM-3 (25 g, 145 mmol) and 4-methylamino-piperidine-1-carboxylic acid-tert-butylester SM-5a (40.36 g, 188 mmol) in dry AcCN (200 mL) and stirred for 30 h at 65° C. After the reaction is finished the reaction mixture is diluted with AcCN and water and stirred for 15 min. The precipitated product is collected by filtration, washed with water and the solid is dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | 1-Boc-4-(methylamino)piperidine (800mg, 3.7mmol), and <strong>[90176-80-0]4-fluoro-2-(trifluoromethyl)benzaldehyde</strong> (0.56mL, 4.lmmol) were dissolved in DCM (l2mL) (plus molecular sieves) and stirred for 2 hours at room temperature. To the clear solution was added sodium triacetoxyborohydride (1 .1 8g, 5.6mmol) and the reaction was stirred over the weekend at room temperature. The reaction was diluted withDCM and then quenched with saturated NaHCO3 solution (aq). The organic and aqueous layers were separated and the aqueous layer further extracted with DCM. The organic layers were combined and concentrated in vacuo to give 1 .6g of crude product as a yellow oil. Purification by silica flash chromatography using 0% EtOAc in heptane with a gradient increasing to 50% ethyl acetate afforded tert-butyl 4-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl-methyl-amino]piperidine-1 -carboxylate (1 .1 5g, 2.9mmol, 79%) as a pale yellow/clear oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃; for 12h; | Step 1: To a solution of compound 1c (1 equivalent) in dichloromethane, compound 13a (1.5 eq.) was added sequentially.HOAT (1.5 eq.), HATU (2 eq.), DIPEA (6 eq.), stirred at room temperature for 12 hours.The solvent is then sparged off and directly isolated by column chromatography to afford intermediate 13b. |
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