Structure of 1268810-09-8
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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. : | 1268810-09-8 |
Formula : | C10H15NO2 |
M.W : | 181.23 |
SMILES Code : | O=C(OC(C)(C)C)NC1(C#C)CC1 |
MDL No. : | MFCD22548363 |
InChI Key : | QVGLHHJMUIIWAA-UHFFFAOYSA-N |
Pubchem ID : | 72218569 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.7 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 50.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.51 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.39 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.69 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.56 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.58 |
Solubility | 4.82 mg/ml ; 0.0266 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.8 |
Solubility | 2.88 mg/ml ; 0.0159 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.73 |
Solubility | 3.36 mg/ml ; 0.0185 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 |
-6.42 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 |
1.0 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) |
2.56 |
* 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 |
---|---|---|
Three 250mL flask was added triphenylphosphine (45. 4g, 0 · 17mol, 4eq) and DCM (255g), the reaction solution was cooled down to0~5 C, was added CBr4 (28. 6g, 0. 086mol, 2eq), the red color of the solution no mention, 20min after the solid precipitation.Four batches Compound 2Α (8g, 0. 043πο1, leq), heat obvious, 0 C reaction 0. 5h. The solid was removed by filtration, and concentrated,Brush silica gel, the eluent was concentrated to give a pale yellow solid 13. 7g.[0047] 4 NMR (400MHz, CDC13):... Δ = 6. 687 (s, 1H), 1 453 (s, 9H), 1 288 (m, 2H), 1 253 (m,2H) ppm; ESI / MS: m / z = 342 (Μ + Η) +.[0048] The light yellow solid (270mL) was added in THF, cooled to -78 C, dropping 2. 5Mn-BuLi / hexane solutionLiquid (53mL, 0 130mol, 3eq.), - 78 C reaction 30min, was slowly warmed to -40 C, the reaction 30min. Slowly at -40 CDropwise addition of water (lmL), was slowly warmed to room temperature and extracted with ethyl acetate (100mL * 2), dried and concentrated to give a solid. N-heptylDioxane (20g) was added to the solid, stirred 30min, filtered and dried to afford Compound 3A as a white solid (6. 6g, yield:84%, purity: 94.1%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | three flask was added compound 24 (28,0.0111111,169) and 01 ^ (201 ^), added dropwise at room temperatureTCA (2 · 6g, 0 · 016mol, 1 · 5eq), at room temperature was added in three portions sodium trichloroacetate (3g, 0 · 015mol, 1 · 6eq),Room temperature 4h. Cooled to 0 C, was added dropwise acetic anhydride (2. 2g, 0. 022mol, 2eq), was slowly warmed to room temperature, room temperaturelh. Acetic acid (25mL), cooled to 0 C, was added zinc dust (1.48,0.02 111,269), warmed to 55~60 (:, transShould lh. Slow cooling to room temperature, water (200 mL), filtered, MTBE extract (50mL * 2), the combined organic phases with saturated common saltWashed with water (30mL * l), the organic phase was concentrated, brush silica, eluant was concentrated to give a pale yellow solid 2. 4g.2. 4g solid was added to the three 100mL flask was added THF (30mL), cooled to -30 C, was added dropwise 1. 6M AButyl lithium / diethyl ether solution (18mL, 0. 03mol, 3eq), low temperature reaction lh, slowly warmed to room temperature. Aqueous solution of ammonium chloride(100 mL), extracted with ethyl acetate (50mL * 2), and the combined organic phase was concentrated to give a solid, n-heptane (10g) was added to the solid,Stirred for 30min, filtered and dried to afford Compound 3A as a white solid (1. 5g, Yield: 77%, purity: 952%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | 250mL three neck flask was added triphenylphosphine (11. 3g, 0. 044mol, 4eq) and DCM (255g), the reaction solutionCooled to 0~5 C, was added CC14 (11. 4g, 0 · 022mol, 2eq), stirred for 30min. Compound was added in four batches2Α (2g, 0. 01 lmo 1,1 eq), heat obvious, 0 C reaction 0. 5h. Filtered to remove solids, and concentrated, brush silica gel, eluent concentrationCondensing pale yellow solid 2. 5g. ESI / MS: m / z = 253 (M + H) +.[0078] (50mL) of the pale yellow solid was added THF, cooled to -78 C, was added dropwise 2. 5Μ n-BuLi / hexane solution(13mL, 0 · 033mol, 3eq), - 78. . The reaction 30min, slowly warmed to -40. . The reaction 30min. -40. . Slowly droppedWater (50 mL), was slowly warmed to room temperature and extracted with ethyl acetate (50mL * 2), dried and concentrated to give a solid. N-Heptane (10g)Was added to the solid, stirred for 30min, filtered and dried to afford Compound 3A as a white solid (1. 45g, yield: 74%, pureDegree: 95 · 1%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
250mL three neck flask was added triphenylphosphine (11. 3g, 0 · 044mol, 4eq) and DCM (255g), the reactionWas cooled to 0~5 C, was added CI4 (11. 4g, 0. 022mol, 2eq), stirred for 30min. Four batches Compound 2Α (2g, 0. 01 lmo 1,1 eq), heat obvious, 0 C reaction 0. 5h. Filtered to remove solids, and concentrated, brush silica gel, eluent concentrationReduced to give a yellow solid 4. 3g. ESI / MS: m / z = 436 (M + H) +.[0073] (50mL) of the pale yellow solid was added THF, cooled to -78 C, was added dropwise 2. 5Μ n-BuLi / hexane solution(13mL, 0 · 033mol, 3eq), - 78. . The reaction 30min, slowly warmed to -40. . The reaction 30min. -40. . Slowly droppedWater (50 mL), was slowly warmed to room temperature and extracted with ethyl acetate (50mL * 2), dried and concentrated to give a solid. N-Heptane (10g)Was added to the solid, stirred for 30min, filtered and dried to afford Compound 3A as a white solid (1. 55g, yield: 79%, pureDegree: 94 · 6%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Dimethyl (1-diazo-2-oxopropyl)phosphonate (443 mL) was dissolved in MeCN (0222) (25 mL) and potassium carbonate (767 mg) was added. The suspension was stirred at room temperature for 10 minutes, then the freshly prepared aldehyde 14 (428 mg) in MeOH (9 mL) was added. Stirring was continued overnight. The solvents were removed in vacuo and the residue was dissolved in 1 :1 mixture of Et20/water. The layers were separated and the organic layer was washed with water and brine, and dried (Na2S04). The yellowish oil was purified by FCC (1 :2 EtOAc/heptane) to give product 15 as a pale white solid. 1H NMR (300 MHz, CDCIs) d = 5.00 (s, 1 H), 2.13 (s, 1 H), 1.46 (s, 9H), 1.23 - 1.16 (m, 2H), 1.12 - 1.01 (m, 2H). 13C NMR (75 MHz, CDCIs) d = 155.47, 85.80, 80.34, 66.75, 28.49, 23.72, 18.13. |