Structure of 33985-71-6
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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. : | 33985-71-6 |
Formula : | C13H15NO |
M.W : | 201.26 |
SMILES Code : | O=CC1=CC2=C(N3CCC2)C(CCC3)=C1 |
MDL No. : | MFCD00151555 |
InChI Key : | XIIVBURSIWWDEO-UHFFFAOYSA-N |
Pubchem ID : | 98700 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.46 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 64.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.31 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.15 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.82 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.76 |
Solubility | 0.349 mg/ml ; 0.00174 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.35 |
Solubility | 0.891 mg/ml ; 0.00443 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.35 |
Solubility | 0.0905 mg/ml ; 0.00045 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) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
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) |
Yes |
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 |
-5.9 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 |
0.0 |
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) |
1.79 |
* 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 |
---|---|---|
1g | With acetic anhydride; for 3h;Inert atmosphere; Reflux; | A mixture of 9-aldehyde julolidine (0.7 g), Was fully dissolved in acetic anhydride (10 ml) and added under argonInto the malononitrile (2.2g),Stirring reaction under reflux reaction 3h. After the reaction, quenching, caustic washing, washing,Dried, concentrated, and TLC (PE: EA = 3: 1) to give 1.0 g of 9- (2,2-dinitrile vinyl) julolidine as a red solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With trichlorophosphate; In dichloromethane; at 20℃; for 4h;Inert atmosphere; | Julolidine (0.5 g, 2.89 mmol), DMF (0.255 g, 3.49 mmol)and POCl3 (0.535 g, 3.49 mmol) were dissolved in DCM(15 mL) and the mixture was stirred at room temperaturefor 4 h under an inert argon atmosphere. The solution?scolor turned green and the degree of advancement was followedby TLC. The solution was treated with aq. NaOH(2 M) and the crude product then was extracted withEt2O. After two aqueous washings, the organic phase wasdried on MgSO4, filtered and concentrated under vacuum.The product was then purified on column chromatographyusing 40%-50% Et2O: Hexane was used as the eluentto give 0.48 g (83.08%) (the reaction yield was upto 92% when 1.5 g julolidine was used as starting material)of a light yellow solid product.1H NMR (300 MHz,CDCl3: = 9597 (s, 1 H), 7.29 (s, 1 H), 3.308 (t, J =57 Hz, 4 H), 2.787 (t, J = 62, 4 H), 2.002-1.92 (m, J =63, 4 H). |
80% | 2,3,6,7-Tetrahydro-1H,5H-pyrido[3,2,1-ij]quinoline-9-carbaldehyde was synthesized according to the described method [Kauffman, Joel M.; Imbesi, Steven J.; Aziz, Mohammed Abdul - Organic Preparations and Procedures International, 2001, vol. 33, 6, p. 603 - 613] with some modifications: to a magnetically stirred solution of POCl3 (2.2 ml, 23 mmol) in DMF (2 ml) julolidine (2) (2 g, 11.6 mmol) and DMF (2 mL) under argon was added dropwise at 0 C. Then the mixture was allowed to stir for 3 h at rt (TLC). Ammonium hydroxide was added for neutralization and the solution was deluted with ethyl acetate and washed with water several times. The residue was purified by column chromatography (silica gel, 10% ethyl acetate/hexane). Yield 1.8 g (80%). 1H NMR (300 MHz, CDCl3): delta 9.63 (s, 1H), 7.28 (s, 2H), 3.31 (t, J=5.8 Hz, 4H), 2.81 (t, J= 6.2 Hz, 4H), 1.97-2.06 (m, 4H). | |
71% | With trichlorophosphate; In N,N-dimethyl-formamide; at 90℃; for 4.5h; | The synthesis of 9-formyljulolidinewas carried outmodifying a reported procedure [45,46]. In brief,phosphorous oxychloride (1.1 mL, 11.55 mmol) was added dropwise to N,N-dimethyl-formamide(2 mL, 25.85 mmol) at 0 C. A solution of julolidine (2.0015 g, 11.55 mmol) in DMF (3.5 mL, 45.24 mmol)was then added and the mixture was stirred at 90 C for 4.5 h. The solution was allowed to coolat room temperature (rt) and neutralized to pH 6-8 by the addition of a saturated sodium acetatesolution (~30 mL). After stirring overnight at rt, a greenish-yellow solid precipitate was recoveredvia filtration, washed with water (30 mL) and dried under high vacuum. The crude product waspurified through column chromatography on silica gel using ethyl acetate/CHCl3 (70/30 v/v) aseluent mixture. 1.65 g of FJUL were recovered (71% yield). FT-IR (KBr, cm-1): 2758, 1651, 1594,1527, 1321. 1H-NMR (CDCl3): delta (ppm) = 9.6 (s, 1H, CHO), 7.3 (s, 2H, aromatic), 3.3 (t, J = 5.8 Hz,4H, NCH2), 2.7 (t, J = 6.3 Hz, 4H, NCH2CH2CH2), 1.9 (m, 4H, NCH2CH2). 13C-NMR (CDCl3): delta (ppm) = 190.1 (-CHO), 147.9 (-N-C(-C-)=C-), 129.5 (-C(=C)-CH=C(-C)-CH=), 124.0 (-CH-(CH=)C-CHO),120.33 (-CH2-C(=C-)-CH(=C)), 50.0 (-N(-CH2)-), 27.7 (-N(-CH2-CH2-CH2-)-), 21.3 (-N(-CH2-CH2-CH2-)-).EI-MS m/z (%): 201 (100, M+). |
60% | With trichlorophosphate; In dichloromethane; at 25℃; for 8h; | In brief, phosphorous oxychloride (0.29 mL, 3.17 mmol) was added dropwise to a solution of julolidine(0.5 g, 2.88 mmol) and N,N-dimethylformamide (0.27 mL,3.45 mmol) in anhydrous dichloromethane (5 mL) and the mixture was stirred for 8 h at 25 C. The reaction was treated with an aqueous solution of sodium hydroxide (2 M) and the mixture was stirred at 0 C for 4 h. The organic layer was extracted with diethyl ether, dried over Na2SO4 and evaporated to dryness under reduced pressure. The crude product was purified by column chromatography on silica gel (230400 mesh) using diethyl ether/n-hexane (3/7 v/v) as eluent mixture (Rf 0.37) (60% yield). FT-IR (KBr, cm1): 2950, 2895, 1662, 1600, 1320, 900, 720.1H NMR (CDCl3) (ppm): 9.6 (s, 1H, CHO), 7.3 (s, 2H, aromatic), 3.3(t, 4H NCH2), 2.7 (t, 4H NCH2CH2CH2), 1.9 (m, 4H NCH2CH2).13C NMR (CDCl3) (ppm): 191.3 (CHO), 149.1 (CeN aromatic),128.5 to 122.0 (aromatic), 49.3 (NCH2), 28.1 to 20.4 (NCH2CH2CH2). EI-MS m/z (%): 201 (100, M). |
42.7% | With trichlorophosphate; at 80 - 100℃; for 2h;Inert atmosphere; Cooling with ice; | Dry N,N-dimethylformamide (DMF) (3.4 mL, 43.9 mmol) was charged into around bottom flask fitted with a magnetic stirrer and pressure-equalizing dropping funnel. The flask was purged withdry nitrogen and cooled in an ice bath. Phosphorus oxychloride (0.79 mL, 8.5 mmol) was then added slowly to the DMF. A solution of 2,3,6,7-tetrahydro-1H,5H-benzo-quinolizine(julolidine) (1.47 g, 8.5 mmol) in DMF (1.36 mL) was then added with vigorous stirring to the mixture and the resulting mixture was heated at 80-100 C for 2 h. The solution was allowed to cool to room temperature and was poured into ice water. The solution was neutralized to pH 6-8 by addition of saturated sodium acetate. The desired aldehyde precipitated out of solution as a greenish-yellow solid. The solid was filtered, washed with water and hexane, and dried to obtain pure aldehyde 1 (0.731 g). Yield: 42.7%. 1H NMR (500 MHz, CDCl3) delta 1.37 (p, 2x2H), 2.8 (t, 2x2H),3.3 (2x2H, t), 7.29 (2x1H, s), 9.6 (s, 1H, CHO). |
1.1 1: Phosphorus oxychloride (1.17 g, 7.62 mmol) was slowly added dropwise to a round bottom flask containing DMF (1.67 g, 22.87 mmol) in an ice salt bath. After the addition was completed, the ice bath was removed. Vilsmeier-Haack reagent was prepared by stirring at room temperature for half an hour under nitrogen.Then, a DMF solution in which julolidine (1.2 g, 6.93 mmol) was dissolved was slowly added dropwise thereto, and after completion of the dropwise addition, it was refluxed at 90 C for 4 hours. Pour the reacted material into ice water to make it reverseShould stop, continue to stir for at least 2h, a yellow solid precipitated,Finally, suction filtration gave a pale yellow solid. |
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