Structure of 57184-23-3
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CAS No. : | 57184-23-3 |
Formula : | C11H22N2 |
M.W : | 182.31 |
SMILES Code : | N1(CC2CCCCC2)CCNCC1 |
MDL No. : | MFCD01075237 |
InChI Key : | LRPGNFROBDUREU-UHFFFAOYSA-N |
Pubchem ID : | 2735885 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 64.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
15.27 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.77 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.81 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.88 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.09 |
Solubility | 1.5 mg/ml ; 0.00821 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.93 |
Solubility | 2.16 mg/ml ; 0.0118 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.22 |
Solubility | 1.1 mg/ml ; 0.00605 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 |
No |
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) |
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 |
-6.01 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 |
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) |
1.76 |
* 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 |
---|---|---|
In ethyl acetate; at 70℃; for 6h; | Die nachfolgenden Verbindungen der Beispiele 8 bis 65 wurden nach einem automatisierten Herstellungsverfahren hergestellt.Hierzu wurde pro Ansatz eine Lösung von 0,03 mmol (2R)-1-[3,5- Bis(trifluormethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(4-azido-2-butin-1-yl)piperazin der Formel IV (Herstellung siehe Beispiel 1/Syntheseweg 1B)) in 1 ml Ethylacetat jeweils mit einer Lösung von 0,03 mmol des als Reaktionspartner vorgesehenen sekundären Amins der Formel V in 1 ml Ethylacetat umgesetzt und anschließend mit 3 ml Ethylacetat verdünnt. Auf das Reaktionsgemische wurde Stickstoffgas gegeben und es wurde jeweils 6 Stunden lang bei 70 C gerührt. Der Reaktionsendpunkt wurde Dünnschicht-chromatographisch bestimmt. Nach vollendeter Umsetzung wurden die einzelnen Reaktionsgemische jeweils im Vakuum zur Trockene eingedampft. Aus dem Rückstand wurde ohne weitere Aufreinigung jeweils eine Probe für die Hochleistungs-Flüssigkeitschromatographie (= HPLC) und für die automatische Massenspektroskopie zur Bestimmung der Reinheit bzw. zur Strukturbestätigung entnommen. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 110℃; for 4.83h; | Example 39; Synthesis of (3,5-bis-trifluoromethyl-benzyl)- [2-(4-cyclohexylmethyI-piperazin-l-yl)- quinolin-3-ylmethyl]-carbamic acid ethyl ester; Step (i): Synthesis of 2-(4-cyclohexylmethyl-piperazin-l-yl)-quinoline-3-carbaldehyde; l-(Cyclohexylmethyl)piperazine (0.42 niL, 2.2 mmol) was added to a mixture of 2-chloro-3-quinolinecarboxaldehyde (0.383 g, 2.0 mmol) and potassium carbonate (0.7 g, 5.0 mmol) in anhydrous DMF (4 mL) at ambient temperature under a nitrogen atmosphere. After being stirred for 20 minutes, the reaction mixture was heated at 110 C for 4.5 h. After cooling to room temperature this mixture was diluted with water (40 mL) and extracted with ethyl acetate (3 x 30 mL). The combined organic extracts were EPO <DP n="205"/>washed with brine, dried over sodium sulfate, filtered, and then concentrated under vacuum to give a pale brown crude product. Purification by silica gel column chromatography and eluting with 2.5% methanol in dichloromethane afforded the title compound (0.56 g), yield: 86%.Mp 95-96 C;1H NMR (CDCl3, 300 MHz): δ 10.17 (s, IH), 8.48 (s, IH), 7.81 (t, J= 8.2 Hz, 2H), 7.67(m, IH), 7.36 (m, IH), 3.51 (t, J= 5.1 Hz, 4H), 2.61 (t, J= 4.8 Hz, 4H), 2.22 (d, J= 7.2Hz, 2H), 1.84-1.68 (m, 6H), 1.31-1.13 (m, 3H), 0.96-0.82 (m, 2H).777/z MS: 338 (M++., 100%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | 4-Cyclohexylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-phenoxy)-phenyl Ester The hydrochloride of the title compound was prepared from 4-(4-trifluoromethyl-phenoxy)-phenyl chloroformate and 1-cyclohexylmethyl-piperazine, yield 93%. White crystals, m.p. 256-258 C.; IR (KBr): ν 1715 (C=O) cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | 4-Cyclohexylmethyl-piperazine-1-carboxylic Acid 4-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-phenyl Ester The hydrochloride of the title compound was prepared from 4-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-phenyl chloroformate and 1-cyclohexylmethyl-piperazine, yield 76%. White crystals, m.p. 265-266 C.; IR (KBr): ν 1732 (C=O) cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.75 g (100%) | EXAMPLE 22 1-(Cyclohexylmethyl)-4-[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxybutyl]piperazine STR39 Reaction of N-(cyclohexylmethyl)piperazine and 4-[(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yl)oxy]butyric acid (2 g) analogously to the procedure of Example 4 gave the title compound after crystallization from methanol/diethyl ether as the hydrated dihydrochloride salt; yield 3.75 g (100%), m.p. 258-260 C. (dec). Anal. Calcd. for C25 H33 N5 O3.2HCl.0.4 H2 O: C, 56.48; H, 6.79: N, 13.18; H2 O, 1.36. Found: C, 56.72: H, 7.47; N, 12.47; H20, 0.35%. 1 H-NMR (DMSO-d6) delta 0.93 (2H, q, J=11 Hz), 1.15 (3H, m), 1.50 to 1.95 (6H, m), 2.01 (2H, t, J=6 Hz), 2.58 (2H, m), 2.90 to 3.20 (4H, m), 3.33 (1H, t, J=12 Hz), 3.44 (2H, bs), 3.77 (1H, t, J=12 Hz), 4.08 (3H, t, J=6 Hz), 4.39 (1H, d, J=12 Hz), 7.24 (1H, dd, J=9 Hz, J1 =2.5 Hz), 7.44 (1H, dd, J=2.5 Hz), 7.72 (1H, s), 7.84 (1H, d, J=9 Hz), 11.13 (1H, bs), 11.50 (2H, bs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N-methyl-acetamide; dichloromethane; | Example 1 1-[3-(4-Cyclohexanemethyl-1-piperazinyl)-propyl]-2(1H)-quinolinone 1-(3-Bromopropyl)-2(1H)-quinolinone (250 mg) obtained in Preparation example 1, cyclohexanemethylpiperazine (171 mg), and potassium carbonate (195 mg) were suspended in dimethylformamide (3 ml). The suspension was heated at 80C for 10 hr. Dichloromethane was added to the reaction solution. The mixture was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under the reduced pressure to give an oil. The oil was purified by column chromatography on silica gel to give the title compound (272 mg). 1H NMR (CDCl3) δ (ppm): 0.80 - 0.98 (2H, m), 1.09 - 1.30 (3H, m), 1.42 - 1.55 (1H, m), 1.61 - 1.80 (5H, m), 1.93 (2H, tt, J = 7.7 and 7.2 Hz), 2.13 (2H, d, J = 7.2 Hz), 2.36 - 2.58 (8H, m), 2.48 (2H, t, J = 7.2 Hz), 4.35 (2H, t, J = 7.7 Hz), 6.69 (1H, d, J = 9.5 Hz), 7.18- 7.24 (1H, m), 7.50 - 7.58 (3H, m), 7.66 (1H, d, J = 9.5 Hz). Mass spectrum EIMS, m/z 367 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20℃; | General procedure: The basic substituent was introduced in the 6th-position of chlorokojic acid via a Mannich-type reaction, using formaline and an appropriate substituted piperidine or piperazine derivatives in methanol at room temperature. The reaction proceeded very rapidly. Mannich bases were prepared by the reaction of substituted piperazine or piperidine derivatives and chlorokojic acid in MeOH with 37% formaline. The mixture was stirred vigorously for 15-25min at room temperature. The resulting precipitate was collected by filtration and washed with cold MeOH. Formation of the desired new Mannich base derivatives were confirmed on the basis of elemental analysis, and the structures of the compounds were supported by spectral data. Chlorokojic acid; Yield 60%, mp: 166-167C. 6-(Chloromethyl)-3-hydroxy-2-((4-(4-iodophenyl)piperazin-1-yl)methyl)-4H-pyran-4-one (Compound 9) C17H18ClIN2O3, yield: 56%; mp: 182-3C; %CHN Found (Calculated): C 44.65 (44.32), H 3.91 (3.94), N 6.61 (6.08); IR ν (cm-1): 1630 (C=O), 1456 (C=C), 1202 (C-O); 1H NMR (DMSO-d6, 400MHz) δ ppm: 2.60 (4H; t; J=4.8; piperazine-H2′, H6′), 3.13 (4H; t; J=4.8; piperazine-H3′,H5′), 3.62 (2H; s; -CH2-), 4.66 (2H; s; ClCH2-), 6.55 (1H; s; H5), 6.76 (2H; d; J=9.2; Ar-H2″, H6″), 7.46 (2H; d; J=9.2; Ar-H3″, H5″), 9.22 (1H; s; -OH); 13C NMR (DMSO, 400MHz) δ ppm: 42.11, 48.35, 52.77, 54.02, 81.32, 113.12, 118.49, 137.93, 144.82, 148.14, 151.19, 161.93, 174.15; ESI-MS (m/z): 399 (100%), 461 (M++H), 463 (M++H+2), 483 (M++Na). Ethyl 4-((6-(chloromethyl)-3-hydroxy-4-oxo-4H-pyran-2-yl)methyl)piperazine-1-carboxylate (Compound 24) C14H19ClN2O5, yield: 63%; mp: 136-7C; %CHN Found (Calculated): C 50.59 (50.84), H 5.63 (5.79), N 8.38 (8.47); IR ν (cm-1): 1679 (C=O), 1424 (C=C), 1220 (C-O); 1H NMR (DMSO-d6, 400MHz) δ ppm: 1.67 (3H; t; J=7.0; -CH3), 2.44 (4H; t; J=5.2; piperazine-H2′, H6′), 3.36 (4H; t; J=5.2; piperazine-H3′,H5′), 3.60 (2H; s; -CH2-), 4.02 (2H; q; J=6.8; -CH2CH3), 4.65 (2H; s; ClCH2-), 6.55 (1H; s; H5), 9.19 (1H; br s; -OH); 13C NMR (DMSO, 400MHz) δ ppm: 15.22, 42.10, 43.93, 52.62, 53.10, 61.39, 113.12, 144.86, 147.90, 155.23, 161.94, 174.16; ESI-MS (m/z): 331 (M++H), 333 (M++H+2), 353 (M++Na, 100%). Benzyl 4-((6-(chloromethyl)-3-hydroxy-4-oxo-4H-pyran-2-yl)methyl)piperazine-1-carboxylate (Compound 25) C19H21ClN2O5, yield: 64%; mp: 141-2C; %CHN Found (Calculated): C 57.86 (58.09), H 5.25 (5.39), N 7.07 (7.13); IR ν (cm-1): 1679 (C=O), 1446 (C=C), 1225 (C-O); 1H NMR (DMSO-d6, 400MHz) δ ppm: 2.45 (4H; t; J=4.8; piperazine-H2′,H6′), 3.40 (4H; m; piperazine-H3′,H5′), 3.60 (2H; s; -CH2-), 4.65 (2H; s; ClCH2-), 5.07 (2H; s; -CH2COO-), 6.55 (1H; s; H5), 7.28-7.38 (5H; m; Ar-H), 9.20 (1H; br s; -OH); 13C NMR (DMSO, 400MHz) δ ppm: 42.10, 44.15, 52.64, 54.01, 66.89, 113.12, 128.20, 128.50, 129.09, 137.57, 144.82, 148.05, 155.05, 161.92, 174.17; ESI-MS (m/z): 393 (M++H), 395 (M++H+2), 415 (M++Na, 100%). 1-((6-(Chloromethyl)-3-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-4-phenylpiperidine-4-carbonitrile (Compound 26) C19H19ClN2O3, yield: 71%; mp: 156-7C; %CHN Found (Calculated): C 64.35 (63.60), H 5.39 (5.34), N 7.91 (7.81); IR ν (cm-1): 1660 (C=O), 1455 (C=C), 1200 (C-O); 1H NMR (DMSO-d6, 400MHz) δ ppm: 1.99-2.56 (8H; m; piperidine); 3.68 (2H; s; -CH2-), 4.66 (2H; s; ClCH2-), 6.56 (1H; s; H5), 7.34-7.54 (5H; m; Ar-H); 9.24 (1H; br s; -OH); 13C NMR (DMSO, 400MHz) δ ppm: 36.15, 42.09, 42.29, 50.69, 54.03, 113.19, 122.67, 126.33, 128.75, 129.71, 140.82, 144.87, 148.19, 161.95, 174.19; ESI-MS (m/z): 381 (100%, M++Na), 359 (M++H), 361 (M++H+2). 6-(Chloromethyl)-3-hydroxy-2-((4-phenyl-5,6-dihydropyridin-1(2H)-yl)methyl)-4H-pyran-4-one (Compound 27) C18H18ClNO3, yield: 76%; mp: 165-6C; %CHN Found (Calculated): C 64.67 (65.16), H 5.33 (5.47), N 4.16 (4.22); IR ν (cm-1): 1622 (C=O), 1456 (C=C), 1198 (C-O); 1H NMR (DMSO-d6, 400MHz) δ ppm: 2.49-3.19 (6H; m; pyridine), 3.69 (2H; s; -CH2-), 4.67 (2H; s; ClCH2-), 6.14 (1H; t; J=3.6; pyridine), 6.55 (1H; s; H5), 7.22-7.42 (5H; m; Ar-H); 13C NMR (DMSO, 400MHz) δ ppm: 27.99, 42.13, 50.20, 52.76, 53.62, 113.13, 122.47, 125.24, 127.69, 129.04, 134.55, 140.75, 144.76, 148.52, 161.94, 174.18; ESI-MS (m/z): 332 (100%, M++H), 334 (M++H+2), 354 (M++Na). 6-(Chloromethyl)-2-((4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)methyl)-3-hydroxy-4H-pyran-4-one (Compound 28) C18H17Cl2NO3, yield: 97%; mp: 166-7C; %CHN Found (Calculated): C 59.15 (59.03), H 4.61 (4.68), N 4.01 (3.82); IR ν (cm-1): 1631 (C=O), 1458 (C=C), 1194 (C-O); 1H NMR (DMSO-d6, 400MHz) δ ppm: 2.47-3.27 (6H; m; pyridine), 3.69 (2H; s; -CH2-), 4.66 (2H; s; ClCH2-), 6.18 (1H; br s; pyridine), 6.55 (1H; s; H5), 7.36 (2H; d; J=8.4; Ar-H2″, H6″), 7.44 (2H; d; J=8.4; Ar-H3″, H5″); 13C NMR (DMSO, 400MHz) δ ppm: 27.86, 42.13, 50.08, 52.70, 53.55, 113.13, 123.38, 127.02, 128.92, 132.19, 133.46, 139.54, 144.76, 148.47, 161.94, 174.17; ESI-MS (m/z): 218 (100%), 366 (M++H), 368 (M++H+2), 388 (M++Na). 6-(Chloromethyl)-2-((4-(4-fluorophenyl)-5,6-dihydropyridin-1(2H)-yl)methyl)-3-hydroxy-4H-... |