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[ CAS No. 136888-21-6 ] {[proInfo.proName]}

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Chemical Structure| 136888-21-6
Chemical Structure| 136888-21-6
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Product Details of [ 136888-21-6 ]

CAS No. :136888-21-6 MDL No. :MFCD06659490
Formula : C5H2ClFN2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :SVVZGNAZMPSGMU-UHFFFAOYSA-N
M.W : 176.53 Pubchem ID :10773626
Synonyms :

Calculated chemistry of [ 136888-21-6 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 38.03
TPSA : 58.71 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.14 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.06
Log Po/w (XLOGP3) : 1.74
Log Po/w (WLOGP) : 2.2
Log Po/w (MLOGP) : 0.31
Log Po/w (SILICOS-IT) : 0.37
Consensus Log Po/w : 1.14

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.37
Solubility : 0.756 mg/ml ; 0.00428 mol/l
Class : Soluble
Log S (Ali) : -2.59
Solubility : 0.454 mg/ml ; 0.00257 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.3
Solubility : 0.887 mg/ml ; 0.00502 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 3.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.03

Safety of [ 136888-21-6 ]

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 [ 136888-21-6 ]

* 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.

  • Upstream synthesis route of [ 136888-21-6 ]
  • Downstream synthetic route of [ 136888-21-6 ]

[ 136888-21-6 ] Synthesis Path-Upstream   1~8

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Reference: [1] Patent: CN107827887, 2018, A,
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  • [ 136888-20-5 ]
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YieldReaction ConditionsOperation in experiment
70% With benzyltrimethylammonium chloride; trichlorophosphate In acetonitrile at 80℃; for 6 h; a)
Synthesis of 2-chloro-5-fluoro-3-nitro-pyridine
5-fluoro-3-nitro-pyridin-2-ol (2 g, 12.7 mmol) and benzyltrimethyl ammonium chloride (1.17 g, 6.35 mmol) were dissolved in acetonitrile, and phosphorus oxychloride (3.5 ml, 38.1 mmol) was added thereto and stirred at 80° C. for 6 hours.
The reaction mixture was cooled and poured into ice water to quench the reaction, and extracted with dichloromethane.
The combined organic layer was washed with saturated saline solution, dried over anhydrous sodium sulfate (Na2SO4), filtered and evaporated under reduced pressure.
The residue was purified by column chromatography on silica eluding with a solvent of dichloromethane:methanol=30:1.
The fractions containing the product were collected and evaporated to obtain yellow liquid (1.57 g, 70percent).
1H-NMR (CDCl3, 300 MHz); δ=8.56 (d, J=2.7 Hz, 1H), 8.40 (dd, J=6.5 Hz, 2.7 Hz, 1H).
MS (ESI); 176.9 (M++1).
69% With tetraethylammonium chloride; trichlorophosphate In acetonitrile at 90℃; for 24 h; PREPARATION 53
2-Chloro-5-fluoro-3-nitropyridine
5-Fluoro-3-nitro-pyridin-2-ol (1.00 g, 5.33 mmol) was dissolved in acetonitrile (40 mL) and tetraethylammonium chloride (2.10g, 12.65 mmol) was added.
The mixture became clear, phosphorous oxytrichloride (1.94 g, 12.65 mmol) was added at room temperature and the mixture was heated at 90 ºC for 24h.
The reaction mixture was evaporated to dryness; the residue was taken up with water (100 mL) and extracted with ethyl acetate (2x100 mL).
The organic layer was dried with sodium sulfate, filtered and evaporated to dryness.
A yellow solid (0.90 g, 69percent) was isolated, pure enough to perform the next synthetic step.
LRMS (m/z): 177 (M+1)+
41% at 110℃; for 18 h; A mixture of the pyridine of preparation 55 (105 mg, 0.66 mmol), phosphorus oxychloride (1 ml) and Λ/,Λ/-dimethyIformamide (10 μl, catalytic) was heated at 11O0C for 18 hours. The cooled reaction mixture was then concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel using dichloromethane/acetonitrile as eluant (100:0 to 50:50 v/v) to yield the title compound (48 mg, 41percent) as a solid. 1H NMR (400MHz, CDCI3): δ 8.03 (dd, 1 H), 8.55 (d, 1 H).
Reference: [1] Patent: US2011/28467, 2011, A1, . Location in patent: Page/Page column 52
[2] Patent: EP2518071, 2012, A1, . Location in patent: Page/Page column 43
[3] Patent: WO2006/114706, 2006, A1, . Location in patent: Page/Page column 45
[4] Journal of Heterocyclic Chemistry, 1996, vol. 33, # 2, p. 287 - 293
[5] Patent: US2004/110785, 2004, A1, . Location in patent: Page 77
[6] Patent: WO2012/146667, 2012, A1, . Location in patent: Page/Page column 97-98
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YieldReaction ConditionsOperation in experiment
65 g With ethylenediaminetetraacetic acid; dihydrogen peroxide; potassium carbonate In water; acetonitrile at 20℃; for 1 h; In a high-pressure reactor, 85 g (0.5 mol) of 2,3-dichloro-5-fluoropyridine was added to 200 mL of ammonia water.Set the temperature to 180 °C, high pressure reaction 24h,TLC detects the reaction of the raw material completely.The solvent was evaporated to give 2-chloro-5-fluoro-3-aminopyridine 65 g;2-chloro-5-fluoro-3-aminopyridine 65 g (0.45 mol)Placed in 900 mL round bottom flask in acetonitrile,Aqueous buffer solution 450mL (0.6M K2CO3-4x10-4M EDTA disodium salt) was added successively,Acetonitrile 350mL (3mol) and 30percent H2O2 in water290mL (3mol),The reaction mixture was stirred at room temperature for 1 hour and extracted with ethyl acetate (3 x 300 mL).Combine organic layers,Dry with anhydrous Na2SO4,Remove the solvent under vacuum to obtain the product of sufficient purity 2-chloro-5-fluoro-3-nitropyridine65g;To a solution of 2-chloro-5-fluoro-3-nitropyridine 65 g (0.35 mol) in DMSO/H2O (9:1, 3500 mL) was added L-Proline 230g (2mol),Na2CO3 210g (2mol),NaN3 230g (3.5mol),Sodium ascorbate 350g (1.75mol) andCuSO4·5H2O500g (2 mol);The mixture was stirred in an oil bath at 70 °C for 24 hours.Then pour the mixture into 10,000 mL of ice water.The solid product was filtered and crystallized to obtain 47 g of 2-amino-5-fluoro-3-nitropyridine.Suggest an editExample 1See also1
65 g With dihydrogen peroxide In water; acetonitrile at 20℃; for 1 h; In a high-pressure reaction vessel, 2,3-dichloro-5-fluoropyridine 85g (0.5 mol) was added to 200 mL of ammonia water, and the temperature was set at 180° C., and the reaction under high pressure was performed for 24 h. The reaction of the starting material was complete by TLC, and the solvent was swirled to obtain 2- Chloro-5-fluoro-3-aminopyridine 65g;Place 2-chloro-5-fluoro-3-aminopyridine 65 g (0.45 mol) in a 900 mL round-bottomed flask in acetonitrile, and add 450 mL of water buffer solution (0.6 M K2CO3-4×10-4 M EDTA disodium salt). 350 mL (3 mol) of acetonitrile and 290 mL (3 mol) of a 30percent H2O2 aqueous solution, and the reaction mixture was stirred at room temperature for 1 hour and extracted with ethyl acetate (3 x 300 mL). The organic layers were combined and dried over anhydrous Na2SO4. The solvent was removed to give a sufficiently pure product, 2-chloro-5-fluoro-3-nitropyridine, 65 g;To a solution of 65 g (0.35 mol) of 2-chloro-5-fluoro-3-nitropyridine in DMSO/H2O (mass ratio 9:1, 3500 mL) was added L-proline 230 g (2 mol), Na2CO3 210 g (2 mol), NaN3 230 g (3.5 mol), sodium ascorbate 350 g (1.75 mol) and CuSO4.5H2O 500 g (2 mol); the mixture was stirred in an oil bath at 70C for 24 hours, and then the mixture was poured into 5000 mL of ice water to give a solid product. Filter and crystallize to obtain 47g of 2-amino-5-fluoro-3-nitropyridine; add 2-amino-5-fluoro-3-nitropyridine to the aqueous solution of sulfuric acid, add a certain amount of chloroacetic acid, and heat to 120°C. After TLC monitored the reaction of the raw materials, the reaction mixture was extracted with methylene chloride. The pH of the organic phase was adjusted to 7-8 with a saturated sodium carbonate solution, and the organic phase was concentrated to obtain 2-amino-5-fluoro-pyridine.
Reference: [1] Patent: CN107903266, 2018, A, . Location in patent: Paragraph 0026; 0027
[2] Patent: CN107827887, 2018, A, . Location in patent: Paragraph 0027; 0028
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  • [ 212268-12-7 ]
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Reference: [1] Patent: EP2471792, 2012, A1, . Location in patent: Page/Page column 39-40
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  • [ 21717-96-4 ]
  • [ 136888-21-6 ]
Reference: [1] Patent: EP2471792, 2012, A1,
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  • [ 51173-05-8 ]
  • [ 136888-21-6 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1996, vol. 33, # 2, p. 287 - 293
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  • [ 136888-21-6 ]
  • [ 212268-12-7 ]
YieldReaction ConditionsOperation in experiment
47 g With sodium azide; copper(ll) sulfate pentahydrate; sodium carbonate; sodium L-ascorbate; <i>L</i>-proline In water; dimethyl sulfoxide at 70℃; for 24 h; In a high-pressure reactor, 85 g (0.5 mol) of 2,3-dichloro-5-fluoropyridine was added to 200 mL of ammonia water.Set the temperature to 180 °C, high pressure reaction 24h,TLC detects the reaction of the raw material completely.The solvent was evaporated to give 2-chloro-5-fluoro-3-aminopyridine 65 g;2-chloro-5-fluoro-3-aminopyridine 65 g (0.45 mol)Placed in 900 mL round bottom flask in acetonitrile,Aqueous buffer solution 450mL (0.6M K2CO3-4x10-4M EDTA disodium salt) was added successively,Acetonitrile 350mL (3mol) and 30percent H2O2 in water290mL (3mol),The reaction mixture was stirred at room temperature for 1 hour and extracted with ethyl acetate (3 x 300 mL).Combine organic layers,Dry with anhydrous Na2SO4,Remove the solvent under vacuum to obtain the product of sufficient purity 2-chloro-5-fluoro-3-nitropyridine65g;To a solution of 2-chloro-5-fluoro-3-nitropyridine 65 g (0.35 mol) in DMSO/H2O (9:1, 3500 mL) was added L-Proline 230g (2mol),Na2CO3 210g (2mol),NaN3 230g (3.5mol),Sodium ascorbate 350g (1.75mol) andCuSO4·5H2O500g (2 mol);The mixture was stirred in an oil bath at 70 °C for 24 hours.Then pour the mixture into 10,000 mL of ice water.The solid product was filtered and crystallized to obtain 47 g of 2-amino-5-fluoro-3-nitropyridine.
Reference: [1] Patent: CN107903266, 2018, A, . Location in patent: Paragraph 0026; 0027
[2] Patent: CN107827887, 2018, A, . Location in patent: Paragraph 0027; 0028
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Reference: [1] Patent: EP2394987, 2011, A1, . Location in patent: Page/Page column 10
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