Structure of 35150-09-5
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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. : | 35150-09-5 |
Formula : | C7H14N2O3 |
M.W : | 174.20 |
SMILES Code : | CC(C)(C)OC(=O)NCC(N)=O |
MDL No. : | MFCD08275106 |
InChI Key : | RHONTQZNLFIDCQ-UHFFFAOYSA-N |
Pubchem ID : | 10910064 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.71 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 43.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
81.42 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.51 |
Solubility | 54.1 mg/ml ; 0.31 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.13 |
Solubility | 13.0 mg/ml ; 0.0748 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.82 |
Solubility | 26.2 mg/ml ; 0.151 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 |
-7.45 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) |
1.96 |
* 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 |
---|---|---|
100% | With Lawessons reagent; In tetrahydrofuran; at 20℃; for 16h; | To compound 386 (21.63 g, 0.124 mol) dissolved in THF (400 mL) was added Lawesson reagent (30.13 g, 0.074 mol). Stirred at room temperature for 16 h then concentrated. Purified by silica gel chromatography (eluant: 3% MeOH- CH2CI2) then re-purified by silica gel chromatography (eluant: 2% MeOH- CH2Cl2) to give 23.59 g (100%) of the product 387 as a light green solid. MS m/e: 135 (M+2-tBu). For n=2: MS m/e: 149 (M+2-tBu) |
78% | With Lawessons reagent; In tetrahydrofuran; at 20℃; for 24h; | Carbamoylmethyl-carbamic acid tert-butyl ester (10.88 grams, 62.46 mmol) and Lawesson's Reagent (15.66 grams, 38.72 mmol) were dissolved in THF (200 ml) and stirred under a nitrogen atmosphere at ambient temperature for 24 hours. The solvent was removed and the residue purified by column chromatography on silica (20% EtOAc/ hexanes) to yield Compound 14.2 (9.21 grams, 48.41 mmol, 78%). IH NMR (400 MHz, DMSO-d6) delta ppm 1.36 (s, 9 H) 3.80 (m, 2 H) 7.03 (m, 1 H) 8.99 (m, 1 H) 9.66 (m, 1 H). |
60% | With Lawessons reagent; In dichloromethane; at 20℃; for 16h;Inert atmosphere; | Lawesson?s reagent (893 mg, 4.25 mmol) was added to a solution of glycineamide (740 mg, 4.25 mmol) in dry CH2Cl2 (50 mL) and the reaction mixture was stirred under N2 atmosphere at room temperature for 16 h. The reaction was quenched by addition of saturated aqueous NaHCO3 and was stirred for 1 h before been extracted with EtOAc (3 x 15 mL). The organic layers were washed with brine (20 mL); dried with MgSO4 and the solvent evaporated under reduced pressure to give the crude product wich was purified by flash chromatography (hexane/ EtOAc, 1:1) to give 8 (466 mg, 60 %) as a white solid. Rf = 0.51 (hexane/ EtOAc, 1:1); 1H NMR (400MHz, CDCl3) delta 1.46 (s, 9H), 4.16 (d, 2H, J = 6.1 Hz), 5.33 (bs, 1H), 7.66 (bs, 1H), 7.89 (bs, 1H). 13C NMR (100MHz, CDCl3) delta 28.3 (3C), 51.4, 81.1, 156.4, 205.1. |
51% | With Lawessons reagent; In tetrahydrofuran; at 20℃;Inert atmosphere; | To a solution of N-Boc-glycinamide (2.5 g, 14.3 mmol, 1 equiv.) in anhydrous THF (20 mL) was added Lawesson's reagent (3.5 g, 8.6 mmol, 1 equiv.) under argon. The reaction mixture was stirred at rt overnight. The solvent was evaporated and the residue purified by flash chromatography using EtOAc/CH2Cl2 (1/9) to give 5 as a white solid (1.4 g, 51%) |
42% | With Lawessons reagent; In dichloromethane; at 20℃; for 12h; | To a solution of Boc-Gly-NH2 (11 g, 62.9 mmol) in CH2Cl2 (300 mL) was added Lawesson's Reagent (13.2 g, 32.7 mmol). After stirring at rt for 12 h, the mixture was concentrated. Purification of the residue (SiO2; 50% Et2O in hexanes) provided the desired product (5.0 g, 42%). |
44 g | With Lawessons reagent; In tetrahydrofuran; at 20℃; for 5h; | Compound 23 (42.59g, 244 . 5mmol) dissolved in tetrahydrofuran (500 ml), cooled to 0 C, plus olausson reagent (59.34g, 146 . 7mmol), stirring at room temperature to 5h, decompression turns on lathe thf, the residue is poured into the ice and saturated sodium bicarbonate solution, ethyl acetate extraction of the organic phase (500mLx3), combined with the phase, the organic phase with saturated salt water washing, dry anhydrous sodium sulfate, concentrated, the residue is dissolved in silica gel column chromatography to obtain white solid compound 24 (44g, 95%). 1 HNMR (400MHz, CDCl 3): delta 7.82 (br, 1H), 7.52 (br, 1H), 5.25 (br, 1H), 4.16 (d, J= 6.0Hz, 2H), 1.46 (s, 9H). |