Structure of 34547-28-9
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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. : | 34547-28-9 |
Formula : | C8H9FN2O |
M.W : | 168.17 |
SMILES Code : | NNC(=O)CC1=CC=C(F)C=C1 |
MDL No. : | MFCD06655053 |
InChI Key : | PFBNINAURUGQRR-UHFFFAOYSA-N |
Pubchem ID : | 3771612 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 41.88 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.55 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.62 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.94 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.03 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.4 |
Solubility | 6.68 mg/ml ; 0.0397 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.28 |
Solubility | 8.84 mg/ml ; 0.0525 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.72 |
Solubility | 0.323 mg/ml ; 0.00192 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 |
-6.94 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 |
2.0 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) |
1.41 |
* 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 |
---|---|---|
86% | With hydrazine hydrate; triethylamine; In acetonitrile; for 3h;Reflux; | General procedure: Aralkanoic acid chlorides 2a-g were synthesized by the reaction of aralkanoic acid 1a-g (1 mmol) in the presence of 1,2-dichloroethane (12 mL) solvent and phosphorous oxychloride(0.4 mL) chlorinating agent under reflux for 3hours. Then, the resulting solution was cooled to room temperature, and the solvent was removed under reduced pressureto afford aralkanoic acid chloride 2a-g, which was directly used in the next step without further purification. Acid chloride 2a-g was dissolved in acetonitrile (80 mL), addeddropwise to a solution containing hydrazine hydrate(1 mmol), TEA (0.5 mL) and acetonitrile (20 mL) and allowed to reflux for 3 hours with monitoring by TLC. After consumption of the starting material, the reaction mixture was cooled to room temperature. Evaporation of the solvent under reduced pressure yielded crude acid hydrazide 3a-g as a white solid on cooling, which was purified by column chromatography and crystallized in methanol [46]. |
69% | With hydrazine; In dichloromethane; at 0℃; for 0.666667h; | A cold (0 oC) solution of hydrazine (4. 5 ML, 144 mmol) in dichloromethane (50 mL) was treated with a dichloromethane solution of (4-fluorophenyl) acetyl chloride (1. 0 g, 5. 8 mmol). The resultant solution was stirred for 40 minutes and water was then added. The layers were separated and the aqueous layer was extracted with dichloromethane and the combined organics were dried over sodium sulfate. Filtration and concentration followed by purification by flash chromatography (5% methanol-dichloromethane gradient elution) provided 2- (4-FLUOROPHENYL) acetic hydrazide (673 mg, 69%) as a white solid. 1H NMR (DMSO-D6) : S 9. 18 (broad, 1 H), 7. 26 (dd, J= 8. 4, 5. 7 Hz, 2 H), 7. 09 (t, J= 8. 4 Hz, 2 H), 4. 21 (broad, 2 H), 3. 31 (s, 2 H) ; MS INTO 169 (M+1), |
With hydrazine; | Step 5: (7S)-3-(Benzyloxy)-N-[(4-fluorophenyl)acetyl]-5-methyl-7-phenyl-4;5,6,7- tetrahydropyrazolo[l,5-α]; A solution of (7S)-3-(benzyloxy)-5-methyl-7-phenyl-4,5,6,7-tetrahydropyrazolo[l,5- a]pyrazine-2-carboxylic acid (148 mg, 0.39 mmol), 2-(4-fluorophenyl)acetohydrazide (99 mg, 0.59 mmol; prepared from 4-fluorophenyl acetyl chloride and hydrazine in a manner similar to that described in J. Heterocyclic Chemistry, 1977, 14, 1123), EDC (113 mg, 0.59 mmol), HOBT (79 mg, 0.59 mmol) and triethylamine (82 μL, 0.59 mmol) in DMF (1 mL) was stirred at room temperature for 1 hour. The DMF was removed in vacuo and the residue was partitioned between water and ethyl acetate, adjusting to a pH of 3 using IN HCl. The layers were then separated and the aqueous layer was extracted with more ethyl acetate (2 x 10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure to give the product as white solid. lH NMR (400 MHz, d6-DMSO) δ 10.2 (s, IH), 9.84 (s, IH), 7.98 (dd, J = 8.4 Hz, IH), 7.72 (d, J = 8.4 Hz, IH), 7.56-7.51 (m, 2H), 7.43- 7.34 (m, 6H), 7.14 (t, J = 8.9 Hz, 2H), 6.97 (d, J = 6.1 Hz, 2H), 5.79 (m, IH), 5.34 (AB quartet, J = 10.9 Hz, 2H), 4.23 (dd, J = 13, 4.7 Hz, IH), 3.84 (dd, J = 13.7, 3.7 Hz, IH), 3.52 (s, 2H), and 2.92 (s, 3H). ES MS (M+l) = 528. |
With hydrazine; In dichloromethane; for 0.75h; | To a solution of hydrazine (0.46 mL, 14.49 mmol, 2.5 equiv) in (¾(¾ (29 mL) was added slowly over 30 sec 2-(4- fluorophenyl)acetyl chloride (0.79 mL, 5.79 mmol, 1.0 equiv). Slight warming of the mixture and white precipitate were observed. After stirring 45 min, the mixture was poured into a saturated aqueous solution of NaHCC^ layered with (¾(¾ forming a thick emulsion. This emulsion was filtered through a medium glass frit to give a biphasic homogenous solution. This was extracted with CH2CI2 (x3). The combined CH2CI2 extracts were dried (Na2S04) and then concentrated in vacuo to provide the title compound (1.22 g, 124% yield) as a white solid. Source of extra mass is unclear as product is of high purity. Extra mass may reflect a measuring error of the acid chloride. XH NMR (400 MHz, CDC13) δ ppm 7.19 - 7.24 (m, 2 H), 6.99 - 7.07 (m, 2 H), 6.60 (s, 1 H), 3.85 (d, J=2.01 Hz, 2 H), 3.52 (s, 2 H); LCMS (ES+, (M+H)+) m/z 169.22. | |
With hydrazine hydrate; triethylamine; In acetonitrile; for 3h;Reflux; | General procedure: Aralkanoic acid chlorides 2 were synthesized by the reaction ofaralkanoic acids 1 (1 mmol) in the presence of 1,2edichloroethane(12 mL) solvent and phosphorous oxychloride (0.4 mL) as chlorinatingagent under reflux for 3 h. Then, the resulting solution wascooled to room temperature, and the solvent was removed underreduced pressure to afford aralkanoic acid chlorides 2, which wasdirectly used in the next step without further purification. Aralkanoicacid chlorides 2 was dissolved in acetonitrile (80 mL), addeddrop wise to a solution containing hydrazine hydrate (1 mmol), TEA(0.5 mL) and acetonitrile (20 mL) and allowed to reflux for 3 h withmonitoring by TLC. After consumption of the starting material, thereaction mixture was cooled to room temperature. Evaporation ofthe solvent under reduced pressure yielded crude substituted aromaticacid hydrazides 3 as a white solid on cooling, which waspurified by column chromatography and crystallized on methanol. |
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