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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
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Structure of 6914-76-7
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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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Search for reports by entering the product batch number.
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CAS No. : | 6914-76-7 |
Formula : | C5H8O2 |
M.W : | 100.12 |
SMILES Code : | O=C(C1(C)CC1)O |
MDL No. : | MFCD00001290 |
InChI Key : | DIZKLZKLNKQFGB-UHFFFAOYSA-N |
Pubchem ID : | 81326 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.8 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 25.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.16 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.61 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.81 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.5 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.85 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.79 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.78 |
Solubility | 16.7 mg/ml ; 0.166 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.97 |
Solubility | 10.8 mg/ml ; 0.108 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.38 |
Solubility | 41.6 mg/ml ; 0.416 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 |
-6.48 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 |
0.56 |
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 |
---|---|---|
119.4 g (84%) | With ammonium hydroxide; thionyl chloride; In water; toluene; | Preparation of 1-Methylcyclopropanecarboxamide A 77.7 weight percent solution of 1-methylcyclopropanecarboxylic acid in toluene (185.66 g of solution; about 144.24 g; 1.44 moles) prepared as described above and toluene (42 mL) were added to a 1-L, 4-necked flask equipped with a magnetic stirrer, an addition funnel, and a nitrogen T inlet linked to a water scrubber. The solution was heated to 45 C. and thionyl chloride (116 mL; 1.58 moles; 1.1 equiv.) was added over 1 hour. The addition was accompanied by gas evolution and a mild endotherm. After the addition was complete the reaction mixture was heated to 80 C. for 5 hours at which point no 1-methylcyclopropanecarboxylic acid was present according to GC analysis. Ammonium hydroxide (28% NH3; 390 mL; 5.76 moles; 4 equiv.) was added to a 2-L, 3-necked flask equipped with a mechanical stirrer and an addition funnel. The contents of the thionyl chloride reaction were placed into the addition funnel and washed in with a little toluene. The ammonium hydroxide was cooled in an ice-acetone bath and the contents of the addition funnel were added over 1 hour such that the reaction mixture was maintained below 25 C. Once the addition was complete the mixture was cooled to 0-5 C. in an ice-water bath for 1 hour. The precipitated 1-methylcycpropanecarboxamide was collected by filtration, washed with ice-cold water, and air-dried to afford 119.4 g (84%) of 1-methylcycpropanecarboxamide as a white solid, mp 144-145 C. 1H NMR (DMSO) delta7.03 (bs, 1H); 6.83 (bs, 1H); 1.19 (s, 3H); 0.89 (m, 2H); 0.45 (m, 2H) |
C-(1-Methylcyclopropyl)methylamine A mixture of 1-methylcyclopropanecarboxylic acid (3.0 g) was heated with thionyl chloride (3.6 g) to reflux for 3 hours. The cooled reaction mixture was poured into a concentrated aqueous ammonia solution. Extraction with diethyl ether gave an organic phase, which was dried over sodium sulfate and concentrated. The residue was treated with lithium aluminum hydride according to method I. In an analogous manner, it is also possible to prepare C-(1-ethylcyclopropyl)methylamine. | ||
Example B20 A solution of 1-methylcyclopropane-1-carboxylic acid (1.24 g, 12.39 mmol) and HOBt (2.47 g, 16.1 mmol) in MeCN (31 mL) was treated portion-wise with EDC (3.09 g, 16.1 mmol), stirred at RT for 2 h, treated with NH4OH (15M, 2.4 mL, 36 mmol) and stirred at RT overnight. The mixture was treated with 50% satd. brine, then solid NaHCO3 until saturated, and extracted with EtOAc (3×). The combined organics were dried over Na2SO4 and concentrated to dryness to afford 1-methylcyclopropanecarboxamide (1.35 g, 110%) which was used without further purification. 1H NMR (400 MHz, DMSO-d6): delta 7.01 (br s, 1H), 6.81 (br s, 1H), 1.20 (s, 3H), 0.92-0.88 (m, 2H), 0.47-0.43 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Hydrazine hydrate (34 mL, 1.1 mol) was added portionwise to a stirred suspension of methyl 3-aminopyrazine-2-carboxylate 37 (21.3 g, 139 mmol) in ethanol (65 mL) at room temperature. The resulting slurry was stirred at 60 C for 2 h, cooled to room temperature, and filtered. The solid was washed with cold ethanol (2 x 25 mL) and dried to a constant weight to afford <strong>[6761-52-0]3-aminopyrazine-2-carbohydrazide</strong> (20.75 g, 97%) as a beige solid. TBTU (5.77 g, 18.0 mmol) was added portionwise over 15 min to a stirred suspension of DIPEA (8.5 mL, 49 mmol), 1-methylcyclopropanecarboxylic acid (1.63 g, 16.3 mmol) and <strong>[6761-52-0]3-aminopyrazine-2-carbohydrazide</strong> (2.50 g, 16.3 mmol) in acetonitrile (40 mL). The mixture was stirred at 80 C for 20 min, and then cooled to 0 C. DIPEA (8.5 mL, 49 mmol) followed by 4-methylbenzene-1-sulfonylchloride (9.34 g, 49 mmol) were added over a period of 15 min. The reaction mixture was brought to reflux and allowed to stir at room temperature for 14 h. The mixture was concentrated, and the residue was diluted with DCM, washed with water and brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 40% ethyl acetate in dichloromethane. After evaporation of the solvent, the resulting solid was triturated with diethyl ether, filtered, washed with the minimum of diethyl ether and dried to afford 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.12 g, 60%). NBS (1.87 g, 10.5 mmol) was added portionwise to a solution of 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.08 g, 9.6 mmol) in THF (30 mL). The reaction mixture was stirred at room temperature for 16 h and concentrated. The residue was dissolved in dichloromethane (150 mL), washed with water (2 x 40 mL), brine, dried over magnesium sulfate and concentrated. After evaporation of the solvents, the crude product was purified by flash chromatography on silica gel eluting with 0 to 10% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 5-bromo-3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.50 g, 88%) as a yellow solid. Bis(triphenylphosphine)palladium(II) chloride (59 mg, 0.08 mmol) was added in one portion to a stirred solution of 5-bromo-3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (500 mg, 1.69 mmol) and hexamethyldistannane (0.49 mL, 2.4 mmol) dissolved in dioxane (8 mL) under argon. The resulting suspension was stirred at 80 C for 1 h. The mixture was evaporated. The crude product was purified by flash chromatography on silica gel eluting with 10 to 30% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)-5-(trimethylstannyl)pyrazin-2-amine 38a (314 mg, 49%) as a yellow crystalline solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium hydroxide; for 3h;Reflux; | To a 500 ml three-neck round bottom flask equipped with a mechanical stirrer,19.8 g,<strong>[15910-91-5]1-methylcyclopropylcarboxamide</strong> (0.2 mol),50 ml of 30% sodium hydroxide solution.With stirring,After heating under reflux for 3 hours,cool down,40 ml of concentrated hydrochloric acid was added dropwise to pH = 1 with stirring,Stir for another half hour.Extracted with methylene chloride,dry,The solvent was removed by evaporation,To give 17.2 g of 1-methylcyclopropylcarboxylic acid,The yield was 86.%Purity> 95% (GC normalization method). |
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