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Chemical Structure| 33985-71-6 Chemical Structure| 33985-71-6
Chemical Structure| 33985-71-6

1,2,3,5,6,7-Hexahydropyrido[3,2,1-ij]quinoline-9-carbaldehyde

CAS No.: 33985-71-6

4.5 *For Research Use Only !

Cat. No.: A535141 Purity: 95%

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Product Details of [ 33985-71-6 ]

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

Safety of [ 33985-71-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Calculated chemistry of [ 33985-71-6 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

20.31 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.15
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.29
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.82
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.19
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.32

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.76
Solubility 0.349 mg/ml ; 0.00174 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.35
Solubility 0.891 mg/ml ; 0.00443 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.35
Solubility 0.0905 mg/ml ; 0.00045 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

Yes
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.9 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.79

Application In Synthesis [ 33985-71-6 ]

* 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.

  • Downstream synthetic route of [ 33985-71-6 ]

[ 33985-71-6 ] Synthesis Path-Downstream   1~25

  • 1
  • [ 479-59-4 ]
  • [ 93-61-8 ]
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  • 2
  • [ 75-52-5 ]
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  • [ 101077-26-3 ]
  • 3
  • [ 33985-71-6 ]
  • [ 93-17-4 ]
  • 2-(3,4-dimethoxy-phenyl)-3<i>c</i>(?)-(2,3,6,7-tetrahydro-1<i>H</i>,5<i>H</i>-pyrido[3,2,1-<i>ij</i>]quinolin-9-yl)-acrylonitrile [ No CAS ]
  • 4
  • [ 33985-71-6 ]
  • [ 872-73-1 ]
  • 1-methyl-2-[2-(2,3,6,7-tetrahydro-1<i>H</i>,5<i>H</i>-pyrido[3,2,1-<i>ij</i>]quinolin-9-yl)-vinyl]-pyridinium; iodide [ No CAS ]
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  • [ 372-09-8 ]
  • [ 111476-00-7 ]
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  • [ 33985-71-6 ]
  • [ 109-77-3 ]
  • [ 58293-56-4 ]
YieldReaction ConditionsOperation 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.
  • 7
  • [ 33985-71-6 ]
  • [ 101077-18-3 ]
  • 8
  • [ 33985-71-6 ]
  • [ 101077-18-3 ]
  • 2,3,6,7-tetrahydro-1<i>H</i>,5<i>H</i>-pyrido[3,2,1-<i>ij</i>]quinoline-9-carboxylic acid [ No CAS ]
  • 10
  • [ 33985-71-6 ]
  • [ 7092-49-1 ]
  • 11
  • [ 33985-71-6 ]
  • [ 22213-35-0 ]
  • 1-(2-difluoroboranyloxy-naphthalen-1-yl)-3-(2,3,6,7-tetrahydro-1<i>H</i>,5<i>H</i>-pyrido[3,2,1-<i>ij</i>]quinolin-9-yl)-propenone [ No CAS ]
  • 12
  • [ 479-59-4 ]
  • [ 68-12-2 ]
  • [ 33985-71-6 ]
YieldReaction ConditionsOperation 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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  • [ 150020-82-9 ]
  • 15
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  • [ 20439-47-8 ]
  • (1R,2R)-N,N'-Bis-[1-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)-meth-(E)-ylidene]-cyclohexane-1,2-diamine [ No CAS ]
  • 16
  • [ 33985-71-6 ]
  • [ 20439-47-8 ]
  • (R,R)-N,N'-bis<(2,3,6,7-tetrahydro-1H,5H-benzo<ij>quinolizin-9-yl)methylene>-1,2-cyclohexanediamine [ No CAS ]
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  • [ 6228-47-3 ]
  • [ 93033-71-7 ]
  • [ 93033-72-8 ]
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  • [ 92510-33-3 ]
  • [ 137334-96-4 ]
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  • [ 15626-30-9 ]
  • [ 90133-88-3 ]
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  • [ 56405-66-4 ]
  • [ 90133-91-8 ]
  • 21
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  • [ 82177-74-0 ]
  • 2,3,5,6,7,9-hexahydro-9-<(2,3,6,7-tetrahydro-1H,5H-benzo<i,j>quinolizin-9-yl)methylene>-1H-benzo<i,j>quinolizinium perchlorate [ No CAS ]
  • 22
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  • [ 83710-66-1 ]
  • [ 83710-97-8 ]
  • 23
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  • [ 108-91-8 ]
  • N-<(2,3,6,7-tetrahydro-1H,5H-benzo<ij>quinolizin-9-yl)methylene>cyclohexylamine [ No CAS ]
  • 24
  • [ 33985-71-6 ]
  • kasugamine [ No CAS ]
  • 3-O-<2,3,4,6-tetradeoxy-2,4-bis<<(2,3,6,7-tetrahydro-1H,5H-benzo<ij>quinolizin-9-yl)methylene>amino>-α-D-arabino-hexopyranosyl>-D-chiro-inositol [ No CAS ]
  • 25
  • [ 33985-71-6 ]
  • 2,3,5,6,7,9-hexahydro-9-<(2,3,6,7-tetrahydro-1H,5H-benzo<i,j>quinolizin-9-yl)methylene>-1H-benzo<i,j>quinolizinium perchlorate [ No CAS ]
 

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