Structure of 35320-22-0
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 35320-22-0 |
Formula : | C3H8N2O |
M.W : | 88.11 |
SMILES Code : | C[C@@H](N)C(N)=O |
MDL No. : | MFCD00672501 |
InChI Key : | HQMLIDZJXVVKCW-UWTATZPHSA-N |
Pubchem ID : | 446080 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 6 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.67 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 22.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
69.11 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.32 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.18 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.28 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.95 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.54 |
Solubility | 308.0 mg/ml ; 3.49 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.42 |
Solubility | 231.0 mg/ml ; 2.63 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.56 |
Solubility | 316.0 mg/ml ; 3.59 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 |
-7.81 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 |
2.0 |
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) |
1.0 |
* 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 hydrogenchloride; sodium hydroxide; sodium hydrogencarbonate; In methanol; chloroform; water; | Step 2 3-Methyl-2-hydroxypyrazine <strong>[35320-22-0]D-alanine amide</strong>(7.5 g, 60.2 mmol) was suspended in MeOH (100 mL). H2 O (10 mL) was added to dissolve the solid. The solution was cooled to -30. Glyoxal (72.2 mmol, 8.28 mL of 40% weight solution) was added in one portion. 12.5 N NaOH (12 mL) was added dropwise over 20 minutes. The resulting mixture was stirred at -30 for 40 minutes then at room temperature for another 3 hours. The reaction mixture was placed in refrigerator overnight. The yellow suspension was cooled to 0 and then treated with concentrated HCl (15 mL) followed by NaHCO3 (12.3 g). The resulting neutral mixture was filtered through a frit. The filtrate was added to H2 O (12 mL) and concentrated to remove MeOH. The residue was treated with 100 mL MeOH and filtered to remove the salt. The filtrate was concentrated again to yield a tacky solid that was shaken with CHCl3 (100 mL). Just enough water was added to make the dark aqueous phase supernatant (~15 mL). This aqueous layer was extracted with CHCl3 (6*, 50 mL portions). The organic layers were combined and dried (MgSO4), filtered and concentrated to yield 3-methyl-2-hydroxypyrazine as an off-white solid. 1 H NMR (400 MHz, CDCl3) delta 12.52 (bs, 1H); 7.37 (d, 2H); 7.14 (d, 2H); 2.48 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; In ethanol; | Step 1 D-alanine amide D-alanine (10 g, 71.6 mmol) was dissolved in EtOH in a pressure vessel. The solution was cooled to -78. NH3 (l) (90 mL) was condensed into the reaction mixture. The pressure vessel was sealed and stirred at room temperature for 2 days. The excess ammonia was released from the vessel. The resulting suspension was concentrated to yield the title compound as a white solid which was dried under hi-vacuum for 16 hours overnight. 1 H NMR (400 MHz, CDCl3) delta (12.52 (bs, 1H); 7.37 (d, 1H); 7.14 (d, 1H); 2.49 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Analogously, starting from (4) and (R)-(-)-2-aminopropanamide, the R-enantiomer can be obtained (m.p. 170 C. dec.), [alpha]D225 -3.0 (C=1.1 DMF). | ||
K is --NH(CH2CH3) or is an aminoacyl residue selected from the group consisting of D-alanylamide, D-alanyl(OH), D-glutamyl(OH), | ||
T is --NH(CH2 CH3) or is an aminoacyl residue selected from the group consisting of D-alanylamide, N(R1)-L-alaninamide, N(R1)-D-alaninamide, D-serylamide, and azaglycylamide, |
J is --NH(CH2 CH3) or is an amino acyl residue selected from the group consisting of D-alaninamide, N-(R0)-D-alaninamide, N-(R0)-L-alaninamide, alpha-aza-glycinamide, D-serinamide, and | ||
J is --NH(CH2 CH3) or is an amino acyl residue selected from the group consisting of D-alaninamide, alpha-aza-glycinamide, D-serinamide, and | ||
D. Coupling of D-alanine amide with L-aspartic acid N-thiocarboxyanhydride The D-alanine amide provided in Part C, 1.1 g (5.1 mmole) is dissolved in 5 ml of tetrahydrofuran and 5 ml of water is added. The clear solution is cooled in ice and 0.89 g (5.1 mmole) of L-aspartic acid N-thiocarboxyanhydride is added in one portion. To this is added as required, 0.5M sodium hydroxide to maintain the mixture at pH 9. After stirring 30 minutes the reaction mixture is washed with ethyl ether, then ethyl acetate and the washes are discarded. The aqueous phase is acidified with dilute hydrochloric acid to pH 5.6 and evaporated to dryness at reduced pressure. The residue is taken up in hot methanol, filtered and the methanol evaporated. The residue is taken up again in hot methanol, filtered and the filtrate decolorized with activated carbon, filtered through diatomaceous earth and the filtrate is evaporated to obtain the crude product. The crude product is dissolved in hot water and filtered, concentrated under a stream of nitrogen to a small volume and cooled to precipitate the title compound. Use of D-2-aminobutyric acid, D-serine, D-valine or D-2-aminopentanoic acid in place of D-alanine in the procedure of Part A above and reacting the N-t-butoxycarbonyl-D-amino carbonyl-D-amino acids thus obtained in the procedures of Parts B, C and D, similarly provides the corresponding compounds of formula (I) wherein R is 3,5-dimethyl-1,2-dithiolan-4-yl and Ra is C2 H5, CH2 OH, (CH3)2 CH, or CH3 CH2 CH2, respectively. | ||
Xaa11 is a hydroxy group or an amino acid amide selected from the group consisting of D-alanylamide, D-alanylethylamide, azaglycylamide, glycylamide, glycylethylamide, serylamide, D-serylamide, | ||
A compound according to claim 1 wherein Xaa11 is selected from the group consisting of D-alanylamide, D-alanylethylamide, azaglycylamide, NH-cyclobutyl, NH-cycloheptyl, NH-ethyl, glycylamide, glycylethylamide, NH-hexyl, ... | ||
Xaa11 is a hydroxy group or an amino acid amide selected from the group consisting of: alanylamide, D-alanylamide, alanylethylamide, D-alanylethylamide, azaglycylamide, glycylamide, glycylethylamide, N-methyl-D-alanylamide, serylamide, ... | ||
A compound according to claim 1, wherein Xaa11 is selected from the group consisting of alanylamide, D-alanylamide, alanylethylamide, D-alanylethylamide, azaglycylamide, NH-cyclobutyl, NH-cycloheptyl, NH-ethyl, NH-glycyl, ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; potassium carbonate; In methanol; | 58.0 Parts of D-alanine methyl ester hydrochloride is shaken with 83 parts by volume of a 5 M potassium carbonate solution. The resulting mixture is then extracted three times with portions of methylene chloride. The methylene chloride extracts are combined, dried over anhydrous magnesium sulfate, and stripped to a low volume under reduced pressure. The oily residue is dissolved in a solution of 310 parts of methanol and 200 parts by volume of liquid ammonia and allowed to stand at room temperature for 24 hours. Removal of the solvent under reduced pressure affords an oil, which upon trituration with ethyl ether and cooling, crystallizes. The crystalline material is filtered, dried under vacuum, and recrystallized from isopropyl acetate, to afford D-alanine amide, melting at about 75-80 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium azide; copper(ll) sulfate pentahydrate; trifluoromethylsulfonic anhydride; potassium carbonate; In methanol; dichloromethane; water; for 16h; | Synthesis of 1-007D-Ala-NH0 1-007Tf20 (12 mL, 71 mmol) is added to a mixture of NaN3 (23 g, 350 mmol), H20 (100 mL), and CH2C12 (200 mL) at 0 C. The mixture is stirred at 0 C for 2h, then the layers are separated. The aqueous layer is extracted with CH2C12 (2 x 50 mL). The combined extracts are added to a stirring mixture of D-Ala-NH2 (4.4 g, 35 mmol), K2CC>3 (7.3 g, 53 mmol), 0.3 M CuS04-5H20 (1.2 mL, 0.35 mmol), H20 (200 mL), and MeOH (400 mL). The resulting mixture is stirred for 16 h, then evaporated, and diluted with H20 (50 mL). The mixture is concentrated, H20 (100 mL) is added, and the mixture is extracted with EtOAc (3 x 100 mL). The extracts are combined, washed with brine (100 mL), dried over Na2S04, filtered, and concentrated to provide 1-007 as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 48h;Inert atmosphere; | General procedure: To an oven-dry ground test tube equipped with a stir bar were added 1 mmol 2-bromoiodobenzene, 1mmolL-alaninamide, 3 mmol potassium carbonate and 5 mL DMF. The test tube was sealed with a rubber stopperand was evacuated and refilled with argon for three times. Then the test tube was stirred in an oil bathpreheated at 90? C for 48 hours. After the test tube was cooled to room temperature, the reaction wasquenched with water, and the reaction mixture was extracted with 20 mL ethyl acetate for three times. Thecombined organic layer was washed with 10 mL water and then saturated sodium chloride aqueous solution,and dried over anhydrous sodium sulfate. After filtration, the filtrate was condensed on a rotary evaporator invacuum. The resulting crude product was chromatographed on silica gel (300-400 mesh) with a 1:2 volumeratio mixed solution of ethyl acetate and petroleum ether as eluent to give a white solid L-N-phenylalaninamide. |