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[ CAS No. 5521-38-0 ] {[proInfo.proName]}

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Chemical Structure| 5521-38-0
Chemical Structure| 5521-38-0
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Product Details of [ 5521-38-0 ]

CAS No. :5521-38-0 MDL No. :MFCD00511837
Formula : C12H17N3O3 Boiling Point : -
Linear Structure Formula :- InChI Key :WVNPWSRYQDRSIS-UHFFFAOYSA-N
M.W : 251.28 Pubchem ID :2763936
Synonyms :

Calculated chemistry of [ 5521-38-0 ]

Physicochemical Properties

Num. heavy atoms : 18
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.5
Num. rotatable bonds : 4
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 77.49
TPSA : 72.53 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.12 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.02
Log Po/w (XLOGP3) : 1.0
Log Po/w (WLOGP) : -0.05
Log Po/w (MLOGP) : 0.91
Log Po/w (SILICOS-IT) : -0.97
Consensus Log Po/w : 0.58

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.01
Solubility : 2.45 mg/ml ; 0.00976 mol/l
Class : Soluble
Log S (Ali) : -2.11
Solubility : 1.94 mg/ml ; 0.00773 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.8
Solubility : 3.99 mg/ml ; 0.0159 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 1.0 alert
Brenk : 2.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.14

Safety of [ 5521-38-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 5521-38-0 ]

* 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 [ 5521-38-0 ]
  • Downstream synthetic route of [ 5521-38-0 ]

[ 5521-38-0 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 103-76-4 ]
  • [ 350-46-9 ]
  • [ 5521-38-0 ]
YieldReaction ConditionsOperation in experiment
97% With potassium carbonate In dimethyl sulfoxide at 80℃; for 16 h; To a stirred suspension of 1—fluoro—4—nitrobenzene (2 g,14.17 mmol) and potassium carbonate (3.92 g, 28.3 mmol) in anhydrous dimethyl sulfoxide (10 mL) was added 2— (piperazin—1—yl)ethanol (2.089 mL, 17.01 mmol) and the mixture was heated at 80 °C for 16 hours. After coolingthe mixture was partitioned between water (100 mL) and ethyl acetate (30 mL) . The aqueous layer was separated and extracted with ethyl acetate (2 x 30 mL) . The combined organic fractions were reduced in vacuo. The residue was triturated in water (100 mL) . The solid wascollected by filtration under vacuum and dried for 16 hours under vacuum and flowing nitrogen to give the title compound (3.45 g, 97 percent) . ‘H NMR (400 MHz, CDC13) : 3 8.11 (d, 2H), 6.82 (d, 2H), 3.68 (t, 2H), 3.44 (t, 4H), 2.67 (t, 4H), 2.62 (t, 2H), 2.55 (br s, 1H) . LCMS (Method C):RT = 0.45 mi m/z = 252 [M+H].
95.6% With triethylamine In dimethyl sulfoxide at 90℃; To a solution of l-fluoro-4-nitrobenzene (4.23 g, 30 mmol, 1.0 eq.) in DMSO (40 mL) was added TEA (9.1 g, 90 mmol, 3.0 eq.) followed by 2-(piperazin-l-yl)ethanol (3.9 g, 30 mmol, 1.0 eq.) and the mixture was stirred at 90 °C overnight. The mixture was poured into ice-water (400 mL), filtered and dried in vacum to afford 2-(4-(4-nitrophenyl)piperazin- l-yl)ethanol as a yellow solid (7.2 g, 95.6percent).
86% With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 5 h; Step: 3A-lSynthesis of 2-[4-(4-Nitro-phenyI)-piperazin-l-yl]-ethanol. Procedure:K2C03 (3.912g, 0.02834mol) followed by 1 -Fluoro-4-nitro-benzene (2g, 0.01417mol) was added to a solution of 2-Piperazin-l-yl-ethanol (5.21ml, 0.0425 lmol) in DMF (10ml) and the reaction flask was maintained at 80°C for 5hrs. The reaction was monitored by the TLC (10percent MeOH: CHC13). The resultant was quenched with ice to afford 3g (86percent yield) of 2-[4-(4-Nitro-phenyl)-piperazin-l-yl]-ethanol as a yellow solid.
72% With N-ethyl-N,N-diisopropylamine In acetonitrile for 15 h; Reflux; Sealed tube; Inert atmosphere [00212] Step 1 : To a solution of 4-fluoronitrobenzene (2.0g, 14.16 mmol) in AcN (15 mL), 2-(piperazin-l-yl)ethanol (1.85 g, 14.17mmol) and DIEA (2.97 mL, 17.01 mmol) were added. The mixture was refluxed for 15 h (in a sealed tube). After cooling, the resulting mixture was poured to water (300 ml). The mixture was stirred at room temperature for 30 min. The solids were collected by filtration and washed with water to afford the the desired product as off white solids (2.74g, 72percent yield). ESI-MS calcd for (C12H17N303) 251, found 252 [M+H]+.

Reference: [1] Patent: WO2015/92431, 2015, A1, . Location in patent: Page/Page column 236
[2] Patent: WO2015/27222, 2015, A2, . Location in patent: Paragraph 0322
[3] Patent: WO2012/59932, 2012, A1, . Location in patent: Page/Page column 112-113
[4] Patent: WO2016/138527, 2016, A1, . Location in patent: Paragraph 00212
[5] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2371 - 2387
[6] Patent: US2003/13708, 2003, A1,
[7] Patent: US2004/87575, 2004, A1,
[8] Patent: US2004/110745, 2004, A1,
  • 2
  • [ 6269-89-2 ]
  • [ 540-51-2 ]
  • [ 5521-38-0 ]
YieldReaction ConditionsOperation in experiment
97% With triethylamine In chloroform at 50℃; A mixture of 1-(4-nitrophenyl)piperazine (5, 2.5 g, 12 mmol), 2-bromoethanol (1.28 mL, 18 mmol) and Et3N (1.6 mL, 18 mmol) wereheated at 50° C in CHCl3 (15 mL) for 30-35 h. Reaction mixturewasthen concentrated under reduced pressure and residue was dissolvedin EtOAc (15 mL). The organic layer was washed with water(10 mL x 3). The combined organic layer was then dried (anhyd.Na2SO4) and was concentrated under reduced pressure. The solidseparated out was washed with distilled hexane and again driedunder high vacuum. The pure yellow crystals were recrystallizedusing EtOAc/Hexane in excellent yield (yield 97percent); mp: 180-184 °C;IR (KBr) v (cm-1): 3019, 2399, 2344, 1597, 1535, 1507, 1476, 1350,1330; 1H NMR (400 MHz, CDCl3): δ 8.12-8.09 (2H, m), 6.83-6.81(2H, m), 3.69 (2H, t, J 5.2 Hz), 3.47-3.43 (4H, m), 2.67 (4H, t,J 5.1 Hz), 2.62 (2H, t, J 5.4 Hz), 2.33 (1H, bs); 13C NMR (100 MHz,CDCl3): δ 154.7, 138.5, 125.9, 112.7, 59.3, 57.9, 52.4, 47.0; HRMS (ESIpositive) m/z calcd. for C12H17N3O3 [M+H]+: 252.1348, found,252.1347; Anal calcd. for C12H17N3O3; C, 57.36; H, 6.82; N, 16.72,found: C, 57.13; H, 6.64; N, 16.60.
Reference: [1] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 204 - 218
[2] Journal of the Brazilian Chemical Society, 2010, vol. 21, # 1, p. 63 - 70
[3] Patent: WO2005/9978, 2005, A1, . Location in patent: Page 59
[4] Patent: WO2005/42518, 2005, A2, . Location in patent: Page/Page column 59
  • 3
  • [ 5521-38-0 ]
  • [ 5521-39-1 ]
YieldReaction ConditionsOperation in experiment
88% With palladium on activated charcoal In methanol at 20℃; To a solution of 2-(4-(4-nitrophenyl)piperazin-l-yl)ethanol (3.6 g, 14.3 mmol) in MeOH (40 mL) was added Pd/C (700 mg) and the resulting mixture was stirred at r.t.overnight. The mixture was filtered, and the filtrate was concentrated to afford 2-(4-(4- aminophenyl)piperazin-l-yl)ethanol (2.8 g, 88percent yield) as yellow solid.
69% With hydrogen In methanol for 2 h; Step: 3A-2Synthesis of 2-[4-(4-Amino-phenyl)-piperazin-l-yl]-ethanol.Procedure:Pd-C (0.3g) was added to a solution of 2-[4-(4-Nitro-phenyl)-piperazin-l-yl]-ethanol (3g, 0.01195mol) in MeOH (20ml) and hydrogenated for 2hrs. The reaction was monitored by the TLC (20percent MeOH: CHC13). The resultant was filtered, washed with MeOH and concentrated to afford 1.8g (69percent yield) of 2-[4-(4-Amino-phenyl)-piperazin-l-yl]-ethanol as a pink solid.
1.10 g With palladium 10% on activated carbon; ammonium formate In ethanol at 50℃; for 1 h; A stirred solution of 2—(4—(4—nitrophenyl)piperazin—1— yl)ethanol (1.2 g, 4.78 mmol) in ethanol (20 mL) washeated to 50 °C. 10percent palladium on carbon (0.254 g, 0.239 mmol) was added followed by portionwise addition of ammonium formate (1.506 g, 23.88 mmol) and the suspension was stirred for 1 hour. The suspension was filtered through Celite® washing with fresh ethanol (20 mL) . Theethanol was removed in vacuo to give the title compound(1.10 g, 104 percent) . ‘H NMR (400 MHz, CDC13) : 3 6.81 (d, 2H),6.66 (d, 2H), 3.69 (t, 2H), 3.09 (t, 4H), 3.02 (br s,3H), 2.74 (t, 4H), 2.66 (t, 2H) . LCMS (Method C): =0.13 mi m/z = 222 [M+H].
Reference: [1] Patent: WO2015/27222, 2015, A2, . Location in patent: Paragraph 0323
[2] Patent: WO2012/59932, 2012, A1, . Location in patent: Page/Page column 113
[3] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2371 - 2387
[4] Patent: US2004/87575, 2004, A1,
[5] Patent: US2003/13708, 2003, A1,
[6] Patent: US2004/110745, 2004, A1,
[7] Patent: WO2015/92431, 2015, A1, . Location in patent: Page/Page column 237
[8] Patent: WO2016/138527, 2016, A1, . Location in patent: Paragraph 00214
[9] European Journal of Medicinal Chemistry, 2019, p. 690 - 709
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