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[ CAS No. 57489-77-7 ] {[proInfo.proName]}

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Chemical Structure| 57489-77-7
Chemical Structure| 57489-77-7
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Product Details of [ 57489-77-7 ]

CAS No. :57489-77-7 MDL No. :MFCD08273918
Formula : C6H3Cl2N3 Boiling Point : -
Linear Structure Formula :- InChI Key :JMTFWCYVZOFHLR-UHFFFAOYSA-N
M.W : 188.01 Pubchem ID :11074154
Synonyms :

Calculated chemistry of [ 57489-77-7 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 43.01
TPSA : 30.19 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.85 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.73
Log Po/w (XLOGP3) : 2.25
Log Po/w (WLOGP) : 2.04
Log Po/w (MLOGP) : 1.78
Log Po/w (SILICOS-IT) : 1.77
Consensus Log Po/w : 1.91

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.03
Solubility : 0.176 mg/ml ; 0.000936 mol/l
Class : Soluble
Log S (Ali) : -2.52
Solubility : 0.568 mg/ml ; 0.00302 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.95
Solubility : 0.212 mg/ml ; 0.00113 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.89

Safety of [ 57489-77-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 57489-77-7 ]

* 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 [ 57489-77-7 ]
  • Downstream synthetic route of [ 57489-77-7 ]

[ 57489-77-7 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 57489-70-0 ]
  • [ 57489-77-7 ]
YieldReaction ConditionsOperation in experiment
86% at 20 - 60℃; for 16 h; Inert atmosphere POC13 (130 mL) was added to pyrazolo[1,5-a]pyrimidine-5,7-diol (10g. 66 rnrnol). The suspension was cooJed to 0 °C ard N,N-dimethylaniline (23 mL. 179 mmoi) was siowy added. After warming to room temperature, the reaction was heated at 60 °C under N2 for 16 hr. Upon coohng, the reactior mixture was concentrated in aeuo to give a brown viscous liquid, which was slowly poured onto ice and aIowed to warm to room temperature. The pH was adjustedpH 8 with saturated NaHCO3. The organic layer was then extracted with CH2C12 (4 x 50 mL), dried (MgSO4), and concentrated in vacuo to give a brown ‘iquid. Purification by flash column chromatography using 1:1 v/v DCM:hexanes to 2:1 v/v DCM:hexanes afforded the title compound (10.7 g, 86percent yield) as a white crystalline solid. MS m/z 189.36 [M+1].
64% at 0 - 60℃; for 16 h; Inert atmosphere Step B - Synthesis of 5,7-dichloropyrazolo[ l,5-a]pyrimidine (lnt-9b)lnt-9a Int-ψbTo pyrazolo[l,5-aJpyrimidine-5,7-diol (Int-9a, 9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 ( 125 mL, 1341.1 mmol). The flask was then cooled to 0 0C and OC2009.701887N, N-dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction mixture was then heated at 60 0C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHCψ3 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2CI2 (4 x 50 mL), dried (Na?Sψ4) and concentrated in vacuo to give a brown liquid (29.8 g). Gradient column chromatography on silica eluting with 50percent CHbCb/hexanes (to elute aniline) followed by 75percent CHaC^/hexanes (to elute product) gave 5,7-dichloropyrazolo[l,5-a]pyrimidine (Int-9b) as a white solid (7.7 g, 40.8 mmol, 64percent).
64%
Stage #1: at 0 - 60℃; for 16 h; Inert atmosphere
To pyrazolo[l,5-a]pyrimidine-5,7-diol (9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 (125 mL, 1341.1 mmol). The flask was then cooled to 0°C and N, N- dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction was then heated at 60°C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHC03 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2CI2 (4 x 50 mL), dried (Na2S04) and concentrated in vacuo to give a brown liquid (29.8 g). Gradient column chromatography on silica eluting with 50percent CHaCLVhexanes (to elute aniline) followed by 75percent CH2Cl2/hexanes (to elute product) gave 5,7-dichloropyrazolo[l,5~ a]pyrimidine as a white solid (7.7 g, 40.8 mmol, 64percent).
Reference: [1] Patent: WO2016/130920, 2016, A2, . Location in patent: Page/Page column 124
[2] Patent: WO2011/2887, 2011, A1, . Location in patent: Page/Page column 86-87
[3] Patent: WO2012/27234, 2012, A1, . Location in patent: Page/Page column 40
[4] ACS Medicinal Chemistry Letters, 2010, vol. 1, # 5, p. 204 - 208
[5] Patent: US2011/294781, 2011, A1, . Location in patent: Page/Page column 20
[6] Patent: WO2012/27240, 2012, A1, . Location in patent: Page/Page column 47; 48
[7] Patent: WO2012/47569, 2012, A1, . Location in patent: Page/Page column 41
[8] Patent: WO2012/47570, 2012, A1, . Location in patent: Page/Page column 41
[9] Journal of Medicinal Chemistry, 2012, vol. 55, # 22, p. 10312 - 10313
[10] Patent: WO2013/16164, 2013, A1, . Location in patent: Page/Page column 55
[11] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 1, p. 126 - 132
  • 2
  • [ 121-69-7 ]
  • [ 57489-70-0 ]
  • [ 57489-77-7 ]
Reference: [1] Patent: EP2621926, 2017, B1,
  • 3
  • [ 1820-80-0 ]
  • [ 105-53-3 ]
  • [ 57489-77-7 ]
Reference: [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 15, p. 6700 - 6715
  • 4
  • [ 57489-77-7 ]
  • [ 99898-84-7 ]
YieldReaction ConditionsOperation in experiment
99% With sodium hydroxide In water at 90℃; for 0.5 h; 1 g of 5,7-dichloropyrazolo [2,5-a] pyrimidine was suspended in 25 mL of 1N aqueous sodium hydroxide solution and heated to 90 ° C,Stir for 0.5 h. The reaction was detected by thin layer chromatography, and after completion of the reaction, the reaction solution was cooled to room temperature.The solution was adjusted to pH = 2 with 1N HCl solution to give a suspension,5-chloropyrazolo [1,5-a] pyridine-7 (4H) -one (0.9 g, yield = 99percent) was obtained by standing filtration.
Reference: [1] Patent: CN107033149, 2017, A, . Location in patent: Paragraph 0110; 0180-0181
[2] Journal of Heterocyclic Chemistry, 1985, vol. 22, # 3, p. 601 - 634
  • 5
  • [ 57489-77-7 ]
  • [ 114040-06-1 ]
YieldReaction ConditionsOperation in experiment
92% With N-Bromosuccinimide; ammonium cerium(IV) nitrate In acetonitrile for 1 h; Heating / reflux To a solution of 5, 7-CHLOROPYRAZOLO [1, 5-A] PYRIMIDINE (1 g, 5.32 MMOL) in ACETONITRILE (20 CM3) was added N-BROMOSUCCINIMIDE (1.04 g, 5. 85 MMOL) and ceric ammoinum nitrate (0.029 g, 0.053 MMOL). The reaction was heated at reflux for 1 hour. The reaction was washed with aqueous sodium metabisulfite (30 CM3, 10percent solution) and then brine (20 cm3). The organic fraction was dried with magnesium sulphate and CONCENLRATED IN VACUO. The product was purified on silica ELUTING with 20percent ETHYLACETAT in hexane, to yield the title compound as A yellow solid (1. 33 g, 92percent). δH (400 MHz; d4-CDCl3) 8.22 (1H, s), 7.04 (1H, s).
89% With N-Bromosuccinimide In acetonitrile at 20℃; for 2 h; To a solution 5,7-dichloropyrazolo[l ,5-a]pyrimidine (246.6 g, 1.31 mol) in CH3CN (1.8 L) was added NBS (245 g, 1.38 mol ). The resulting mixture was stirred at room temperature for 2 hours. After removal of the solution, the reaction mixture was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 :5) to give the title compound (3 13.5 g, 89percent) as light yellow solid. NMR (300 MHz, CDCl3): 5 7.04 (s, 1 H), 8.21 (s, 1 H); MS ESI [M + H]+265.9, calcd for [C6H2BrCl2N3+H]+265.9.
89% With N-Bromosuccinimide In acetonitrile at 20℃; for 2 h; Inert atmosphere To a stirred solution of sodium ethoxide in EtOH, which was prepared from sodium (281.3 g, 12.0 mol) and EtOH (10 L) by the conventional method, were added diethyl malonate (963.7 g, 6.02 mol) at ambient temperature and then compound lH-pyrazol-3-amine (500 g, 6.02 mol). The reaction mixture was refluxed for 12 hours. After cooled to room temperature, the precipitates were collected by filtration and dissolved in water. The aqueous solution was acidified with 2 M HC1 (pH = 2). The resulting precipitates were collected by filtration and dried under reduced pressure to afford pyrazolo[l,5-a]pyrimidine- 5,7(4H,6H)-dione (649 g, 71percent) as a yellow solid, which was used for the next reaction without further purification. A stirred suspension of pyrazolo[l,5-a]pyrimidine-5,7(4H,6H)-dione (265 g, 1.75 mol) and NN-dimethylaniline (335.6 mL) in POCl3 (2.00 kg, 13.2 mol) was refluxed for 4 hours. After cooled to room temperature, the reaction mixture was poured into ice-water, and stirred for 30 min, neutralized with saturated aqueous sodium carbonate and extracted with EtOAc. The combined organic layers were washed with water, brine and dried over MgSC>4, filtered and evaporated. The residue was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 : 10) to give 5,7- dichloropyrazolo[l,5-a]pyrimidine (287 g, 87percent) as a yellow solid. To a solution 5,7-dichloropyrazolo[l,5-a]pyrimidine (246.6 g, 1.31 mol) in CH3CN (1.8 L) was added NBS (245 g, 1.38 mol ). The resulting mixture was stirred at room temperature for 2 hours. After removal of the solution, the reaction mixture was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 :5) to give the title compound (313.5 g, 89percent) as light yellow solid. l NMR (300 MHz, CDCl3): δ ppm 7.04 (s, 1H), 8.21 (s, 1H); MS ESI [M + H]+ 265.9, calcd for [CgHzBrC Ns + H]+ 265.9.
Reference: [1] Patent: WO2004/87707, 2004, A1, . Location in patent: Page 33; 34
[2] Patent: WO2014/75168, 2014, A1, . Location in patent: Page/Page column 53
[3] Patent: WO2015/70349, 2015, A1, . Location in patent: Page/Page column 22; 23
[4] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 7, p. 671 - 675
[5] Journal of Medicinal Chemistry, 2012, vol. 55, # 15, p. 6700 - 6715
[6] Patent: WO2004/76458, 2004, A1, . Location in patent: Page 155-156
[7] Patent: US4838925, 1989, A,
[8] Patent: US2006/135514, 2006, A1, . Location in patent: Page/Page column 67-68
[9] Journal of Medicinal Chemistry, 2012, vol. 55, # 22, p. 10312 - 10313
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