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[ CAS No. 676602-31-6 ] {[proInfo.proName]}

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Chemical Structure| 676602-31-6
Chemical Structure| 676602-31-6
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Product Details of [ 676602-31-6 ]

CAS No. :676602-31-6 MDL No. :MFCD06203915
Formula : C9H6FNO2 Boiling Point : -
Linear Structure Formula :- InChI Key :UCOJKDQJOVWXRE-UHFFFAOYSA-N
M.W : 179.15 Pubchem ID :45790123
Synonyms :

Calculated chemistry of [ 676602-31-6 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.11
Num. rotatable bonds : 2
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 42.39
TPSA : 50.09 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) : -6.26 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.91
Log Po/w (XLOGP3) : 1.59
Log Po/w (WLOGP) : 1.9
Log Po/w (MLOGP) : 1.71
Log Po/w (SILICOS-IT) : 2.11
Consensus Log Po/w : 1.84

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.16
Solubility : 1.23 mg/ml ; 0.00689 mol/l
Class : Soluble
Log S (Ali) : -2.25
Solubility : 1.0 mg/ml ; 0.00558 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.84
Solubility : 0.261 mg/ml ; 0.00146 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.86

Safety of [ 676602-31-6 ]

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 [ 676602-31-6 ]

* 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 [ 676602-31-6 ]
  • Downstream synthetic route of [ 676602-31-6 ]

[ 676602-31-6 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 67-56-1 ]
  • [ 201230-82-2 ]
  • [ 179897-89-3 ]
  • [ 676602-31-6 ]
YieldReaction ConditionsOperation in experiment
43% With triethylamine; triphenylphosphine In acetonitrile at 60℃; for 96 h; To CH3CN (100 mL) and MEOH (25 mL) in a sealed tube apparatus is added 5-bromo-2- fluorobenzonitrile (5.00 g, 25. 0 MMOL), TEA (6.97 mL, 50.0 mmol), palladium (II) acetate (393 mg, 1.75 mmol), and triphenylphosphine (269 mg, 1.03 mmol). The reaction is sealed, purged with carbon monoxide twice, and placed under 60 psi of carbon monoxide at 60 C for 4 d. Upon cooling, the reaction is filtered through diatomaceous earth, washing with MeOH. The filtrate is concentrated under reduced pressure, and the residue suspended in 4: 1 EtOAc/Hex (100 mL) then filtered. The filtrate is concentrated under reduced pressure then subjected to flash chromatography (silica gel, CHC13) to afford the sub-title compound (1.91 g, 43percent). 'H NMR (300 MHz, DMSO-d6) 8 3.87 (s, 3H), 7.66 (t, J= 9. 0 Hz, 1H), 8.30 (ddd, J = 2.2, 5.3, 8.6 Hz, 1H), 8.43 (dd, J = 2.2, 6.3 Hz, 1H). FAB MS nez 154 [C9H6FN02 + H-HCN] +, 136 [C9H6FN02 + H-CO2]-
Reference: [1] Patent: WO2004/67529, 2004, A1, . Location in patent: Page 193 - 194
  • 2
  • [ 67-56-1 ]
  • [ 171050-06-9 ]
  • [ 676602-31-6 ]
YieldReaction ConditionsOperation in experiment
95% at 0℃; for 3 h; Heating / reflux Example 1 3,4,5-trimethoxyphenyl-2,4-diaminoquinazoline-6-carboxylate (Compound No. 31)STEP-I: To a solution of 3-cyano 4-fluro benzoic acid (2 g, 0.012 mol) in dry MeOH (20 ml) was added thionyl chloride (1.2 ml, 0.018 mol) at 0 0C and heated to reflux for 3 hours. The reaction mixture was concentrated under vacuum to afford the step-1 product (2 g, 95 percent) as white solid. This was used as such for the next step. Rf = 0.5 (CHCI3: MeOH, 9:1).
87% at 0 - 80℃; for 9 h; To a solution of 3-cyano-4-fluorobenzoic acid (1800 mg, 10.9 mmol) in MeOH (30 mL) was added SOCI2 (1.2 mL) dropwise at 0 °C. After complete addition, the reaction mixture was heated to 80 °C for 9 hours. The solvent was removed under reduced pressure to afford a white solid, which was dissolved in EtOAc. The organic layer was washed with H20, brine, dried over Na2S04, and concentrated to afford the title compound as white solid (1700 mg, 87percent). 1H NMR (400 MHz, CDCI3) δ 8.36-8.30 (m, 2H), 7.33-7.29 (m, 1 H), 3.96 (s, 3H) ppm.
78.1% at 0℃; To a stirred suspension of 16.0 g (96,9 mmol) 2.3.1.a and 161 ml methanol are added 30.4 g (387,6 mmol) acetyl chloride drop wisely at 0°C. The reaction mixture is stirred over night, filtered and concentrated. The residue is diluted with dichloromethane, washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The residue is purified by column chromatography (hexane : ethylacetate). The desired product 2.3.1.b is obtained in 78,1percent yield (13.5 g; 75.7 mmol) MS-ESI: 180 (M+ +1,57), Elementary analysis: Calculated: C 60.34percent H 3.38percent F 10.60percent N 7.82percent Determined: C 60.51percent H 3.39percent F 10.57percent N 7,80percent
78.1% at 0℃; b) Synthesis of 3-Cvano-4-fluoro-benzoic acid methyl ester 2:To a stirred suspension of 16.0 g (96,9 mmol) 1 and 161 ml methanol were added 30.4 g (387,6 mmol) acetyl chloride drop wisely at 00C. The reaction mixture was stirred over night, filtered and concentrated. The residue was diluted with dichloromethane, washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The residue was purified by column chromatography (hexane : ethylacetate). The desired product 2 was obtained in 78,1percent yield (13.5 g; 75.7 mmol) MS-ESI: 180 (M+ +1 , 57), Elementary analysis:Calculated: C 60.34percent H 3.38percent F 10.60percent N 7.82percent Determined: C 60.51percent H 3.39percent F 10.57percent N 7,80percent

Reference: [1] Patent: WO2008/152142, 2008, A1, . Location in patent: Page/Page column 22
[2] Patent: WO2016/120849, 2016, A1, . Location in patent: Page/Page column 81
[3] Journal of Medicinal Chemistry, 2004, vol. 47, # 6, p. 1339 - 1350
[4] Patent: EP1916003, 2008, A1, . Location in patent: Page/Page column 19
[5] Patent: WO2008/28688, 2008, A2, . Location in patent: Page/Page column 74; 75; 87
[6] Patent: WO2011/72488, 2011, A1, . Location in patent: Page/Page column 16; 26
[7] Patent: US2012/283297, 2012, A1, . Location in patent: Page/Page column 17
[8] Patent: WO2004/111052, 2004, A1, . Location in patent: Page 30-31
  • 3
  • [ 171050-06-9 ]
  • [ 74-88-4 ]
  • [ 676602-31-6 ]
YieldReaction ConditionsOperation in experiment
62%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide for 0.166667 h;
Stage #2: for 1 h;
Step 1: Methyl 3-cyano-4-fluoro-benzoate[00441] To a 100 mL round bottom flask was added 3-cyano-4-fluoro-benzoic acid (2.6 g, 15.9 mmol), potassium carbonate (6.6 g, 47.6 mmol), and DMF (30 mL) and the reaction was allowed to stir for 10 minutes. Iodomethane (1.1 mL, 17.5 mmol) was added dropwise and the reaction was allowed to stir for lh. The reaction was complete by lcms. The reaction was quenched with brine and extracted with ethyl acetate. The organic layer was washed with brine 3 times and the organic layer was dried over sodium sulfate and evaporated. Methyl 3-cyano-4-fluoro-benzoate (2.5 g, 62 percent) was isolated as a white solid. ESI-MS m/z calc. 179.0, found 180.0 (M+l) +; Retention time: 1.15 minutes (3 min run).
62%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide for 0.166667 h;
To a 100 mL rbf was added 3-cyano-4-fluoro-benzoic acid (2.6 g, 15.9 mmol) , potassium carbonate (6.6 g, 47.6 mmol), and DMF (30 mL) and the reaction was allowed to stir for 10 minutes. Iodomethane (1.1 mL, 17.5 mmol) was added dropwise and the reaction was allowed to stir for lh . The reaction was complete by lcms. The reaction was quenched with brine and extracted with EtOAC. The organic layer was washed with brine 3 times and the organic layer was dried over sodium sulfate and evaporated. Methyl 3-cyano-4-fluoro-benzoate (2.5 g, 62 percent) was isolated as a white solid. ESI-MS m/z calc. 179.0, found 180.0 (M+1) +; Retention time: 1.15 minutes (3 min run).
62.8%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide for 0.166667 h; Green chemistry
Stage #2: for 1 h; Green chemistry
To a 100 mL rbf was added 3-cyano-4-fluoro-benzoic acid(2.620 g, 15.87 mmol), potassium carbonate (6.580 g, 47.61 mmol), and DMF (30mL) and the reaction was allowed to stir for 10 minutes. iodomethane (2.478 g,1.087 mL, 17.46 mmol) was added dropwise and the reaction was allowed to stirfor 1h. The reaction was complete by lcms analysis. The reaction was quenchedwith brine and extracted with EtOAC. The organic layer was washed with brine 3times and the organic layer was dried over sodium sulfate and evaporated. Methyl3-cyano-4-fluoro-benzoate (2.523 g, 62.8percent) was isolated as a whitesolid . ESI-MS m/z calc. 179.04, found 180.0 (M+1)+; Retention time:1.15 minutesTo a 100 mL rbf was added methyl3-cyano-4-fluoro-benzoate (2.522 g, 62.75percent) followed by DMF (20 mL). sodiumpropane-2-thiolate (3.894 g, 39.68 mmol) was added and the reaction was placedin a preheated 65°C oil bath and allowed to stir overnight. The reaction wasmonitored by lcms and the reaction was complete by lcms analysis. The reactionwas quenched with brine and extracted 3 times with EtOAc. The aqueous layer wasthen treated with commercial bleach (100 mL) and the reaction was allowed tostir for 10 minutes. 1N HCl was then added until pH 1. The reaction was thenextracted with EtOAc and the organic layer was further washed with brine 3times. The organic layer was then dried over sodium sulfate and the solvent wasremoved. 3-cyano-4-isopropylsulfonyl-benzoic acid (2.24 g, 99percent) was isolated asa white solid. 1H NMR (400 MHz, CDCl3)δ 8.59 (d, J = 1.4 Hz, 1H), 8.47 (dd, J = 8.2, 1.7 Hz, 1H), 8.28 (d, J = 8.2Hz, 1H), 3.64 (s, 1H), 1.39 (d, J = 6.8 Hz, 6H).
Reference: [1] Patent: WO2012/112743, 2012, A1, . Location in patent: Page/Page column 164
[2] Patent: WO2013/109521, 2013, A1, . Location in patent: Paragraph 00287; 00288
[3] Tetrahedron Letters, 2014, vol. 55, # 22, p. 3295 - 3298
  • 4
  • [ 75-36-5 ]
  • [ 171050-06-9 ]
  • [ 676602-31-6 ]
Reference: [1] Patent: EP1897885, 2008, A1,
  • 5
  • [ 218301-22-5 ]
  • [ 676602-31-6 ]
Reference: [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 6, p. 1339 - 1350
[2] Patent: WO2004/111052, 2004, A1,
  • 6
  • [ 676602-31-6 ]
  • [ 258273-31-3 ]
Reference: [1] Patent: WO2011/72488, 2011, A1,
[2] Patent: US2012/283297, 2012, A1,
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