Structure of 77497-84-8
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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. : | 77497-84-8 |
| Formula : | C7H13NO2 |
| M.W : | 143.18 |
| SMILES Code : | O=C(OC)CCNC1CC1 |
| English Name : | Methyl 3-(cyclopropylamino)propanoate |
| MDL No. : | MFCD11651272 |
| InChI Key : | IXRSFGOAMNXZBZ-UHFFFAOYSA-N |
| Pubchem ID : | 13041902 |
| Num. heavy atoms | 10 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 0.86 |
| Num. rotatable bonds | 5 |
| Num. H-bond acceptors | 3.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 37.74 |
| TPSA ? Topological Polar Surface Area: Calculated from |
38.33 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.16 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.73 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.24 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.35 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.81 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.86 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-0.86 |
| Solubility | 19.9 mg/ml ; 0.139 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-1.11 |
| Solubility | 11.0 mg/ml ; 0.077 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.39 |
| Solubility | 5.79 mg/ml ; 0.0405 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 |
-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 |
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) |
1.24 |
* 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 benzoic acid; isopentyl nitrite In chloroform at 5℃; for 40h; Title compound not separated from byproducts; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With triethylamine In toluene | 20.a (a) (a) 6-Chloro-4-(N-2-methoxycarbonylethyl-N-cyclopropyl)-amino-pyridine-3-carboxylic acid methyl ester (a compound of formula (VI) in which R=methyl and X=chlorine). A mixture of 28.6 g of β-cyclopropylamino-propionic acid methyl ester and 21 g of triethylamine was rapidly added dropwise to a solution of 41.2 g of 4,6-dichloropyridine-3-carboxylic acid methyl ester in 150 ml of toluene at 10° to 20° C., whilst cooling with ice and stirring. The ice-bath was removed and the mixture was stirred at room temperature for 1/2 hour and heated to the boiling point under reflux for 6 hours. The resulting suspension was washed with water and dried with Na2 SO4 and the solvent was distilled off in vacuo. 59 g of the title compound were obtained as a brown oil. | |
| With triethylamine In toluene | 20.a (a) (a) 6-Chloro-4-(N-2-methoxycarbonylethyl-N-cyclopropyl)-amino-pyridine-3-carboxylic acid methyl ester (a compound of formula (VI) in which R=methyl and X=chlorine). A mixture of 28.6 g of β-cyclopropylamino-propionic acid methyl ester and 21 g of triethylamine was rapidly added dropwise to a solution of 41.2 g of 4,6-dichloropyridine-3-carboxylic acid methyl ester in 150 ml of toluene at 10° to 20° C., whilst cooling with ice and stirring. The ice-bath was removed and the mixture was stirred at room temperature for 1/2 hour and heated to the boiling point under reflux for 6 hours. The resulting suspension was washed with water and dried with Na2 SO4 and the solvent was distilled off in vacuo. 59 g of the title compound were obtained as a brown oil. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In ethanol at 20℃; | 20 Compound 20: 4-(9-cyclopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5- b] [ 1 ,4] diazepin-2-ylamino)-3 -methoxy-iV-( 1 -methylpiperidin-4-yl)benzamide; [0336] The title compound was synthesized using an analogous procedure to that described in connection with Compound 11 except that methyl 3-(cyclopropylamino)propanolate, prepared by Michael addition of ethyl acrylate (1 equiv.) with cyclopropylamine (1 equiv.) in ethanol overnight (see Scheme 2), was used and the final compound was purified by reverse phase HPLC to yield the TFA salt. 1H NMR (400 MHz, DMSO-J6) δ 0.7 (m, 2H), 0.88 (m, 2H), 1.77 (m, 2H), 2.01 (m, 2H), 2.67 (m, 2H), 2.79 (d. J=8 Hz, 3H), 2.93 (m, IH), 3.12 (overlap m&s, 5H), 3.47 (d, J=12 Hz, 2H), 3.80 (m, 2H), 3.96 (s, 3H), 4.14 (m, IH), 7.54 (overlap d & s, 2H), 8.18 (s, IH), 8.35 (d, J=8 Hz, IH), 8.50 (br s, IH), 8.64 (d, J=8 Hz, IH), 9.42 (br s, IH). [M+H] calc'd for C25H33N7O3 479; found, 479. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 92% | With Ps-AlCl3 at 20℃; for 1.5h; chemoselective reaction; | Aza-Michael addition General procedure: In a typical experiment, a mixture of amine (11 mmol), methacrylate or acrylonitrile (2 mmol), and Ps-AlCl3 (0.53 g, 0.24 mmol AlCl3 for aromatic amines; 0.27 g, 0.12 mmol AlCl3 for aliphatic amines) was stirred at 70 C for aromatic amines, room temperature for aliphatic amines. After completion of the reaction, Ps-AlCl3 was filtered and washed with ethyl acetate (3 10 ml), dried, and used in the next run under the same reaction conditions. The filtrate was concentrated to give the crude product, which was purified further by column chromatography (petroleum ether/ethylacetate or methanol/ethyl acetate). |
| 14.2 g | In ethanol at 20℃; for 10h; | 3.1 (1) methyl 3-cyclopropylaminopropionate At room temperature, 8.6g (0.1mol) of methyl acrylate was slowly added dropwise 5.7g (0.1mol) cyclopropylamine in ethanol solution. Maintaining the reaction, it was stirred at room temperature for 10 hours. Distilled under reduced pressure gave 14.2g pale yellow oil. Was used directly without purification in the next step. |
| With Pseudomonas fluorescence lipase immobilized on hyroxypropyl methyl cellulose support In toluene at 50℃; for 3.5h; Enzymatic reaction; chemoselective reaction; | 2.4. Reaction procedure and analysis General procedure: Various β-amino ester moieties were synthesized in a 10 mL glass reaction vessel of 1.2 cm i.d. with a glass lid. The desired Michael acceptor was taken into a reaction vessel and diluted by solvent. Afterwards, Michael donor was added into the reaction vessel and reaction was initiated by addition of immobilized HMC:PFL lipase very soon at a specified temperature. The sample of reaction mixture was analyzed by using gas chromatograph (Perkin Elmer Clarus: 400) having flame ionizing detector (FID) and capillary column. The detector and injector temperature were kept 280 and 50 °C, respectively. The oven temperature of GC was kept at 50 °C for 3 min constant and after that raised with 10 °C/min up to the 280 °C. Moreover, reaction products were also verified by GCMS (Gas-Chromatography-Mass Spectroscopy Shimadzu QP-2010) analysis. |
| In methanol at 20℃; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 2.88 g | With triethylamine In tetrahydrofuran at 20℃; for 2h; | 3.2 (2) Synthesis of Compound 17 1.7g (0.012mol) methyl 3-cyclopropylaminopropionate and 1.52g (0.015mol) of triethylamine were added to 20ml of tetrahydrofuran. Stirring at room temperature, 3.90g (0.010mol) 2-chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)benzene-1-sulfonylchloride and 20ml of tetrahydrofuran were added dropwise and the mixture was stirred at room temperature for 2 hours. Completion of the reaction was monitored by TLC. The mixture was filtered and the filter cake was washed with ethyl acetate. The filtrate was distilled under reduced pressure. The residue was subjected to column chromatography (ethyl acetate: petroleum ether = 1:5 ~ 1:2) to give 2.88g of Compound 17, as a white solid, m.p. 195.8°C. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: hydrogenchloride / water / 24 h / 20 °C 2: hydrogenchloride / water / 20 h / 20 °C |