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[ CAS No. 837-52-5 ] {[proInfo.proName]}

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Chemical Structure| 837-52-5
Chemical Structure| 837-52-5
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Product Details of [ 837-52-5 ]

CAS No. :837-52-5 MDL No. :MFCD01476123
Formula : C13H14ClN3 Boiling Point : -
Linear Structure Formula :- InChI Key :DNXNPMDUDGUXOB-UHFFFAOYSA-N
M.W : 247.72 Pubchem ID :738389
Synonyms :

Calculated chemistry of [ 837-52-5 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 17
Num. arom. heavy atoms : 10
Fraction Csp3 : 0.31
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 78.11
TPSA : 28.16 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.1 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.41
Log Po/w (XLOGP3) : 2.41
Log Po/w (WLOGP) : 1.54
Log Po/w (MLOGP) : 1.99
Log Po/w (SILICOS-IT) : 2.72
Consensus Log Po/w : 2.21

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.26
Solubility : 0.135 mg/ml ; 0.000545 mol/l
Class : Soluble
Log S (Ali) : -2.64
Solubility : 0.563 mg/ml ; 0.00227 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.82
Solubility : 0.00376 mg/ml ; 0.0000152 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.85

Safety of [ 837-52-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338-P310 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 837-52-5 ]

* 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.

  • Upstream synthesis route of [ 837-52-5 ]
  • Downstream synthetic route of [ 837-52-5 ]

[ 837-52-5 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 110-85-0 ]
  • [ 86-98-6 ]
  • [ 837-52-5 ]
YieldReaction ConditionsOperation in experiment
98% at 130℃; for 4 h; Inert atmosphere 4,7-Dichloroquinoline (2.00 g, 10.1 mmol) was combined with piperazine (4.35 g, 50.5 mmol, 5.0 equiv) and neat triethylamine (2.81 mL, 20.2 mmol, 2.0 equiv). The reaction flask was sealed under nitrogen and heated to 130 °C whereupon the solid material gradually melted to give a clear orange-yellow solution. After a period of time, a yellow precipitate was observed. The reaction was completed in approximately 4 hours as determined by TLC (5percent v/v methanol in dichloromethane was used as the solvent system). At this point, the reaction was cooled to room temperature before being diluted with dichloromethane (25 mL) and water (25 mL). The layers were separated and the organic layer was washed with water (3 x 25 mL). The combined aqueous washes were then back-extracted with dichloromethane (50 mL). The combined organic layers were washed with brine (50 mL) and dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give a yellow solid (2.60 g). The crude material was purified by column chromatography over silica gel (dichloromethane/methanol: 100/0 to 98/2) to afford 2.44 g (9.85 mmol, 98percent yield) of the title compound as a yellow solid. The 1H and 13C spectra were consistent with published data. 1H NMR (300 MHz, CDCl3): δ 8.71 (d, J = 4.9 Hz, 1H), 8.03 (d, J = 2.0 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.41 (dd, J = 2.0, 9.0 Hz, 1H), 6.82 (d, J = 5.0 Hz, 1H), 3.17 (obscured br. s, 4H), 3.16 (obscured br. s, 4H); 13C NMR (75 MHz, CDCl3): δ 157.3, 151.9, 150.1, 134.7, 128.8, 126.0, 125.2, 121.9, 108.9, 53.5, 46.0; ESI-MS: m/z 248.
89% With potassium carbonate In 1-methyl-pyrrolidin-2-one at 150℃; for 4 h; Inert atmosphere Piperazine (3.20 g, 36.73 mmol), 4,7-dichloroquinoline (1.5 g, 7.35 mmol) and K2CO3 (0.52 g, 3.76 mmol) were refluxed in anhydrous NMP (10 ml) at 150 °C under N2 and cooled to r.t. after 4 h. The reaction mixture was diluted with CH2Cl2 (50 ml), and washed with H2O (3 x 50 ml), brine (50 ml), dried (Na2SO4) and solvent reduced. The crude material was purified via column chromatography, eluting with MeOH/CH2Cl2 (1:9) to yield the pure material as a white solid (1.62 g, 89percent). m.p. 113 - 116°C (lit. 113 - 115 °C).2 Rf (MeOH/CH2Cl2, 1:9) 0.13. δH (300 MHz; CD3OD) 8.64 (d, J 5.4, 1H, H2), 8.07 (d, J 9.0 Hz, 1H, H5), 7.92 (d, J 2.1, 1H, H8), 7.52 (dd, J 9.0 and 2.1, 1H, H6), 7.01 (d, J 5.4, 1H, H3), 3.31 (pentet, J 1.8, 1H, H11), 3.24 (m, 4H, H9), 3.11 (m, 4H, H10).
80.6% for 16 h; Inert atmosphere To a suspension of 4,7-Dichloro-quinoline (4) (50 g, 0.252 mol) in isopropyl alcohol (150 mL, 3 vol) was added piperazine (65.2 g, 0.757 mol) at ambient temperature. The reaction mixture was stirred under nitrogen at 90 °C for 16 h. The reaction mass was turned into a clear solution at the beginning and the solid precipitation was observed slowly. The progress of the reaction was monitored by TLC analysis. The reaction mass was cooled to room temperature and diluted with ethyl acetate (1L, 20 vol). The unreacted piperazine was precipitated and it was removed by filtration. The filtrated solid was washed with ethyl acetate (500 mL). The filtrate was washed with water (500 mL X 2), dried over solid sulphate and concentrated under reduced pressure to give a crude desired compound. The crude compound was purified by column chromatography using silica gel (60-120), eluent 5 percent methanol in dichloromethane to get the desired compound as a pale yellow solid. Yield; 50 g (80.6 percent)
77.6% for 12 h; Reflux To a stirred solution of 4,7-dichloroquinoline (1) (10 g, 50.49 mmol) in 150 mL ethanol was added piperazine (30.44 g, 353.44 mmol), the resulting solution was then refluxed for 12 h. On reaction completion (TLC) the reaction was then concentrated under vacuum to give a crude solid mixture which was taken up in 200 mL DCM and washed with saturated sodium bicarbonate solution until no piperazine was seen in the organic layer (TLC). The combined organic extracts were dried over anhydrous sodium sulfate and concentrated to give a crude product which was purified by recrystallization in 30percent DCM:Hexane as a white powder (9.7 g, 77.6percent) of compound 2: Rf = 0.25 (10percentMeOH/CHCl3) mp: 118–120 °C; Anal. calcd for C13H14ClN3: C, 63.03; H, 5.70; N, 16.96; found: C, 63.23; H, 5.61; N, 17.02; IR νmax (cm−1): 1652 (C=O), 1579 (C=C); 1H NMR (CDCl3) δ (ppm): 3.14–3.21 (m, 8H), 3.33 (s, 1H), 6.83 (d, 1H J = 5.1 Hz), 7.42 (dd, 1H, J = 2.1 and 9 Hz), 7.97 (t, 1H, J = 9 Hz) 8.06 (dd, 1H, J = 2.1 and 9 Hz), 8.72 (d, 1H, J = 5.1 Hz); FAB-MS (m/z): [M++1] 248.
77% for 12 h; Reflux Piperazine (30.4 g, 353.4 mmol) was added to a mixture of 4,7-dichloro-quinoline 1 (10 g, 50.4 mmol) in ethanol (150 mL). Thereaction mixture was refluxed and stirred for 12 h. The solvent wasremoved in vacuo and the resulting solid mixture was dissolved indichloromethane (200 mL) and washed with saturated sodiumbicarbonate solution until the complete removal of piperazine inthe organic layer (TLC). The combined organic phases were driedover anhydrous Na2SO4, concentrated and then purified byrecrystallization in 30percent dichloromethane/hexane, (yield: 9.7 g 77percent)of compound 2. Mp: 118e120 C; 1H NMR (300 MHz, CDCl3):d 8.72 (d, 1H, J 5.1 Hz), 8.06 (dd, 1H, J 2.1 and 9 Hz), 7.97 (t, 1H,J 9 Hz), 7.42 (dd, 1H, J 2.1 and 9.0 Hz), 6.83 (d, 1H, J 5.1 Hz),3.33 (s, 1H), 3.14e3.21 (m, 8H); IR (KBr) nmax 3342, 3024, 1579,823 cm1; FAB-MS (m/z): [M 1], 248; Anal. calcd for C13H14N3Cl:C 63.03, H 5.70, N 16.96percent; found: C 63.23, H 5.61, N 17.02percent.
70% at 80 - 135℃; for 24 h; General procedure: The amino-functionalized quinolines (7) - (9) were synthesized using a reported method [33], as depicted in Scheme 2 and described as follows: A mixture of 4,7-dichloroquinoline (4.95 g, 25 mmol) and a diamine (250 mmol; 10 eq.) was vigorously stirred upon heating at 80-135 °C for 24h. For the synthesis of the quinolines (10) and (11), a mixture of the quinoline and the diamine was dissolved in anhydrous dimethylformamide (DMF) after which the above described method was applied. The process was monitored by thin layer chromatography. After completion, the mixture was cooled to room temperature while stirring then basified with 1M NaOH (50 ml) and washed with distilled water (150 ml) thereafter the product was extracted with hot EtOAc (3 x 150 ml). The organic phase was dried over MgSO4 for an hour and the solvent removed under reduced pressure. The resulting residue was dissolved in boiling ethyl acetate and allowed to recrystallize at 0-5 °C to afford the amine-functionalized intermediates. The physical data of all compounds are reported.
61.3% With potassium carbonate In acetonitrile at 30 - 80℃; To a suspension of 4,7-dichloroquinoline (2.5g, 12.6mmol) and potassium carbonate (2.1, 15.1mmol) in acetonitrile (20mL) was added piperazine (1.1g, 12.6mmol) at 30°C. The reaction mixture was then heated to 80°C for 1–2h (monitored by TLC and LCMS for completion), cooled to 30°C. The mixture was then filtered through celite bed, and acetonitrile was evaporated in vacuo. The resultant residue was diluted with water (10mL) and dichloromethane (20mL) and the layers separated. The aqueous layer was re-extracted with dichloromethane (2×25mL). The combined organic extract was washed with brine, dried over sodium sulphate, and evaporated in vacuo. The resultant residue was the purified by column chromatography on neutral alumina using hexane: ethylacetate as eluent to give 7-chloro-4-(piperazin-1-yl)quinoline (1.9g, 61.3percent) as an off-white solid. 1H NMR (DMSO-d6): δH. 2.92–3.03 (m, 4H), 3.05–3.13, (m, 4H), 6.95 (d, J=5.1Hz, 1H), 7.52 (dd, J=8.7Hz, J=1.8Hz, 1H), 7.92–8.04 (m, 2H), 8.67 (d, J=4.8Hz, 1H). 13C NMR (DMSO-d6): δC. 156.7, 152.1, 149.6, 133.4, 128, 125.9, 125.5, 121.3, 109.2, 52.8, 45.3. ESI-MS m/z 248.1 (M+1)+. Anal Calcd for C13H14ClN3; C, 63.03; H, 5.70; N, 16.96; Found: 62.99; H, 5.67; N, 16.93.
50% With potassium iodide In isopropyl alcohol for 10 h; Reflux A mixture of4,7-dichloroquinoline (1) (0.505 mol), piperazine (2c) (1.5mol) and potassium iodide (0.12 mol) in isopropyl alcohol(20 ml) was refluxed for 10 h, and cooled to room temperature.The precipitated solid was filtered, washed withisopropyl alcohol and evaporated in vacuo. The crudeproduct, thus obtained was diluted further with dichloromethane(20 ml) and washed twice with water. The pH ofdichloromethane layer was adjusted using conc. HCl. Theseparated water layer was made alkaline with 10percent NaOHsolution and extracted again with dichloromethane. Theorganic layer was evaporated to dryness to get 7-chloro-4-piperazine-1-ylquinoline. Odourless off-white solid; solublein acetone, dichloromethane; melting range 161–162 °C;percentYield 50; Rf value 0.76 (dichloromethane: ethanol: 1:1);Spectroscopic analysis: λmax (in DMSO) 321.52 nm; FTIRSpectrum (νmax, in cm−1, film) 3250.01 (N–H stretching,4NH piprazinyl), 3035.30 (aromatic C–H stretching, quinolyl),2925.41–2830.10 (C–H stretching, 4CH2 piprazinyl),1918.46–1496.85 (N–H bending, 4NH piprazinyl),1452.82–1419.76 (C=C–C, aromatic ring stretching, quinolyl),1373.06–1281.11 (C–N stretching), 1250.50–922.34(aromatic C–H in-plane bend), 1067.64 (C–Cl stretching, quinolyl–Cl), 867.05–618.50 (aromatic C–H out-of-planebend, quinolyl).

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  • 2
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  • [ 837-52-5 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 1, p. 97 - 102
  • 3
  • [ 3412-99-5 ]
  • [ 837-52-5 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 1, p. 97 - 102
  • 4
  • [ 86-99-7 ]
  • [ 837-52-5 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 1, p. 97 - 102
  • 5
  • [ 98-60-2 ]
  • [ 837-52-5 ]
  • [ 774549-97-2 ]
YieldReaction ConditionsOperation in experiment
93.3% With triethylamine In dichloromethane at 0 - 20℃; General procedure: To a stirred solution of 7-chloro-4-piperazin-1-yl-quinoline (2) (0.25 g, 1 mmol) in 8–10 mL of DCM at 0 °C was added triethylamine (0.12 mL, 1.26 mmol). Different aryl sulfonyl chlorides (1 mmol) were added dropwise/portion wise and the resulting solution was stirred further for 15 min at 0 °C and then stirred at room temperature for different time intervals. On reaction completion (TLC), the reaction mix was diluted with 20 mL water and 20 mL DCM and partitioned in separating funnel, where the organic layer was washed with water (3 × 20 mL) before being separated and dried over sodium sulfate to yield compound 3 in which was recrystallized in DCM:Hexane to yield pure products in 85–95percent yields.
Reference: [1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 11, p. 3080 - 3089
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