Structure of 1000796-62-2
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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. : | 1000796-62-2 |
Formula : | C10H21ClN2O2 |
M.W : | 236.74 |
SMILES Code : | O=C(N1CC(N)CCC1)OC(C)(C)C.[H]Cl |
MDL No. : | MFCD06691424 |
InChI Key : | DUNAVVRRZJQGCZ-UHFFFAOYSA-N |
Pubchem ID : | 17750334 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.9 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 66.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.56 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.53 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.77 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.32 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.95 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.07 |
Solubility | 2.0 mg/ml ; 0.00844 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.31 |
Solubility | 1.17 mg/ml ; 0.00495 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.92 |
Solubility | 28.5 mg/ml ; 0.12 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 |
-6.66 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) |
2.71 |
* 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 |
---|---|---|
77% | With sodium hydrogencarbonate; In ethanol; for 4h;Heating / reflux; | tert-Butyl 3-(4-benzylpiperazin-1 -yl)piperidine-1 -carboxylate (XXIc); 4.90 g (21.1 mmol) of benzylbis(2-chloroethyl)amine hydrochloride were dissolved in ethanol (120 ml) and, while stirring, 5.0O g (21.1 mmol) of tert-butyl 3- aminopiperidine-1 -carboxylate hydrochloride and 14.2 g (169 mmol) of sodium bicarbonate were added. The resulting reaction solution was heated under reflux for 4 h. The cooled reaction mixture was concentrated in vacuo, 100 ml of water were added, and the aqueous phase was extracted with ethyl acetate (4x60 ml). The combined organic phases were washed with saturated aqueous NaHCO3 solution, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (mobile phase gradient 0-5% methanol in dichloromethane). Yield: 6.99 g (75%) of yellow solid Yield: 5.82 g (77%) of yellow oil MS (API-ES,pos) m/z = 360 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | Svnthesis 8-1 -B; f-Butyl 3-(4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamido)piperidine-1-carboxylate; A solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (18 mg, 0.09 mmol), HATU (45 mg, 0.12 mmol), and diisopropylethylamine (80 mul_, 0.46 mmol) in DMF (1 mL) was stirred at room temperature for 30 minutes. ferf-Butyl 3-aminopiperidine-1- carboxylate hydrochloride (28 mg, 0.12 mmol) in DMF (0.5 mL) was added and the resulting solution was stirred for 16 hours. The mixture was diluted with brine and extracted with ethyl acetate. The combined organic layers were washed sequentially with NaHCO3 solution, citric acid, and brine, then dried (Na2SO4), filtered, and concentrated. Purification by preparative TLC, eluting with ethyl acetate, gave the title compound as a light yellow oil (10 mg, 29%).1H NMR (500 MHz, CD3OD) delta 1.47 (9H, s), 1.49-1.69 (2H, m), 1.71-1.84 (1 H, m), 2.02- 2.11 (1 H, m), 3.13-3.27 (1 H, m), 3.54-3.68 (1 H, m), 3.86-3.96 (2H, m), 4.00-4.09 (1 H, m), 7.92 (1 H, s), 8.61 (1 H, s); LC-MS Rt 4.29 min; m/z (ESI) 380 [MH+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 140.0℃; for 0.75h;Microwave irradiation; | Example 67A; tert-Butyl 3-[(5-cyanopyridin-2-yl)amino]piperidine-1-carboxylate In analogy to the preparation of Example 60A, 85 mg (56% of theory) of the product are obtained as a solid from 100 mg (0.49 mmol) of <strong>[1000796-62-2]tert-butyl 3-aminopiperidine-1-carboxylate hydrochloride</strong> and 138 mg (0.99 mmol) of 6-chloropyridine-3-carbonitrile.LCMS (method 6): Rt=1.81 min. (m/z=303 (M+H)+)1H-NMR (400 MHz, DMSO-d6): delta=8.40 (d, 1H), 7.68 (d, 1H), 7.53 (d, 1H), 6.59 (d, 1H), 4.12 (s, br, 3H), 3.80 (s, br, 1H), 3.1-3.7 (m, 2H), 1.90 (m, 1H), 1.74 (m, 1H), 1.3-1.6 (m, 1H), 1.27 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Step B tert-butyl 3-aminopiperidine-1-carboxylate hydrochloride Using the compound (2.04 g, 6.17 mmol) obtained in step A and according to the method of Reference Example 9, step C, the title compound (1.45 g, yield 99%) was obtained as a colorless solid. 1H-NMR (300 MHz, DMSO-d6); delta(ppm) 1.3-1.6 (m, 2H), 1.43 (s, 9H), 1.6-1.8 (m, 1H), 1.9-2.0 (m, 1H), 2.7-3.1 (m, 3H), 3.6-3.8 (m, 1H), 3.9-4.0 (m, 1H), 8.23 (brs, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20.0℃; for 16h; | 2- Nitrobenzenesulfonyl chloride (200 mg; 0.90 mmol; 1 eq.), 3- aminopiperidine-1-carboxylic acid tert-butyl ester hydrochloride (320 mg; 1.35 mmol; 1.5 eq.), DIPEA (0.47 mL; 2.71 mmol; 3 eq.), THF anhydrous (10 mL) are stirred at room temperature for 16 h. The reaction mixture is evaporated under reduced pressure, dissolved in EtOAc (50 mL), washed with water (3 x 20 mL) and brine (2 x 10 mL). The organic layer is dried over Na2S04, filtered, and evaporated to dryness. The crude tert-butyl 3- (2-nitrobenzenesulfonamido)piperidine-1-carboxylate (354 mg; 0.90 mmol; 99%; yellow oil; UPLC purity: 98%) is used in the next step without further purification. |
99% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20.0℃; for 16h;Inert atmosphere; | A mixture of2-nitrobenzenesulfonyl chloride4(200 mg; 0.90 mmol; 1 eq.),<strong>[1000796-62-2]tert-butyl 3-aminopiperidine-1-carboxylate hydrochloride</strong> (320 mg; 1.35 mmol; 1.5 eq.), DIPEA (0.47 mL; 2.71 mmol; 3 eq.) in anhydrous THF (10 mL) was stirred at room temperature for 16 h under argon. The reaction mixture was concentratedin vacuo, dissolved in EtOAc (50 mL) and the resulting solution was washed with water, 1 M aq. HCl, sat. aq. NaHCO3and brine. The organic layer was dried over Na2SO4, filtered, and evaporated to dryness. The crudetert-butyl 3-(2-nitrobenzenesulfonamido)piperidine-1-carboxylate (354 mg; 0.90 mmol; yield: 99%; yellow oil; UPLC purity: 98%) was used in the next step without further purification.m/z[M+H]+: 386.05. |
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