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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 1001353-92-9
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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.
4.5
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CAS No. : | 1001353-92-9 |
Formula : | C6H14N2 |
M.W : | 114.19 |
SMILES Code : | N[C@H]1CN(C)CCC1 |
MDL No. : | MFCD17015901 |
InChI Key : | QZSACHHNFDNCNB-ZCFIWIBFSA-N |
Pubchem ID : | 7446917 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H225-H314 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P260-P264-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P321-P363-P370+P378-P403+P235-P405-P501 |
Class: | 8(3) |
UN#: | 2920 |
Packing Group: | Ⅱ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.36 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.7 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.12 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.21 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.27 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.35 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.47 |
Solubility | 38.5 mg/ml ; 0.337 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.04 |
Solubility | 104.0 mg/ml ; 0.91 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.34 |
Solubility | 51.6 mg/ml ; 0.452 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 |
No |
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 |
-7.08 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) |
1.54 |
* 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 |
---|---|---|
40% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20.0℃; | Diisopropylethylamine (509 mg, 3.95 mmole) was added to a mixture of (S)-1-(4-(3-cyclopropyl-1H-pyrazol-5-ylamino)pyrrolo[1,2-f][1,2,4]triazin-2-yl)-4,4-dimethylpyrrolidine-2-carboxylic acid (163H) (300 mg, 0.79 mmol), <strong>[1001353-92-9](R)-1-methylpiperidin-3-amine</strong> (221 mg, 1.58 mmol), and 1-hydroxybenzotriazole (130 mg, 0.95 mmol), N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide hydrochloride (455 mg, 2.37 mmol) in dry dimethylformamide (3 mL) at room temperature. The reaction mixture was stirred at room temperature overnight. The crude product was purified by preparative HPLC. The fractions that contained the product were applied onto a MCX cartridge and then flushed with methanol. The free base of the was eluted with a 2N solution of ammonia in methanol and removal of the solvents gave (163) (150 mg, 40% yield): MS: 478 (M+H)+ HPLC Ret Time: 2.62 min (Phenomenex-Luna S10 4.6*50 mm column, 3 min gradient, 4 mL/min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With formaldehyd; sodium cyanoborohydride; In methanol; water; at 20.0℃; | 163I. (R)-1-methylpiperidin-3-amine Sodium cyanoborohydride (4.51 g, 0.075 mol) was added in portion to a mixture of (R)-tert-butyl piperidin-3-ylcarbamate (10 g, 0.05 mol), 30% water solution of formaldehyde (7.5 mL), and methanol (75 mL) at 0 C. The reaction mixture was stirred at room temperature overnight and concentrated in vacuo. The residue was dissolved in ethyl acetate and water. After extraction, the organic layers were washed with water, brine, and dried over Na2SO4. Concentration in vacuo, gave the N-methyl compound as an oil which was used directly without further purification. To a solution of the crude material previously obtained in methanol (60 mL) was added 4N HCl dioxane (10 mL). The reaction mixture was stirred at room temperature for 6 h. After concentration in vacuo, the residue was triturated with ether. The resulting precipitate was filtered and washed with ice-cold methanol to give the title compound as a solid (4.01 g, 72%). 1H NMR (CD3OD, 400 MHz) delta 3.54 (1H, m), 2.81 (1H, m), 2.62 (1H, m), 2.23 (3H, s), 1.97 (1H, m), 1.67-1.87 (3H, m), 1.56-1.61 (1H, m), 1.41 (9H, s), 1.15-1.42 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20.0℃; | To a solution of Int 13 (342 mg, 1 .001 mmol) and (R)-1 -methylpiperidin-3-amine (149 mg, 1 .301 mmol) in DMF (8 ml.) was added DIPEA (0.524 ml_, 3.00 mmol), HOBt (169 mg, 1 .101 mmol) and EDC (249 mg, 1 .301 mmol). The solution was stirred at RT overnight. The reaction mixture was diluted with 5% Na2CC>3 solution and extracted with EtOAc. The organic layer was washed twice with 5% Na2CC>3 solution, then brine. A white precipitate which formed between the layers was filtered off. The remaining organic extract was dried over Na2S04, filtered and evaporated to give an off-white solid after trituration with DCM. This crude product was combined with the first precipitate and further purified by crystallization from hot MEK to provide the title compound as white crystalline solid. 1 H NMR (400 MHz, DMSO-d6) d (ppm) 7.98 (d, J = 8.0 Hz, 1 H), 7.91 (s, 1 H), 7.53 (s, 1 H), 6.09 (s, 1 H), 4.54 (d, J = 1 .9 Hz, 2H), 3.81 - 3.66 (m, 1 H), 2.66 - 2.57 (m, 1 H), 2.48 - 2.45 (m, overlapping with DMSO signal, 1 H) 2.13 (s, 3H), 1 .98 - 1 .87 (m, 1 H), 1 .86 - 1 .76 (m, 1 H), 1 .71 - 1 .60 (m, 2H), 1 .58 (s, 6H), 1 .52 - 1 .38 (m, 1 H), 1 .27 - 1 .1 1 (m, 1 H). LC-MS: Rt = 0.69 min; MS m/z [M+H]+ 438.2 |
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