Home Cart 0 Sign in  

[ CAS No. 75706-12-6 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 75706-12-6
Chemical Structure| 75706-12-6
Structure of 75706-12-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 75706-12-6 ]

Related Doc. of [ 75706-12-6 ]

Alternatived Products of [ 75706-12-6 ]

Product Details of [ 75706-12-6 ]

CAS No. :75706-12-6 MDL No. :MFCD00867593
Formula : C12H9F3N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :VHOGYURTWQBHIL-UHFFFAOYSA-N
M.W : 270.21 Pubchem ID :3899
Synonyms :
SU101;HWA486;Leflunomide, Arava, Leflunomidum, HWA-486;HW 486;Arava;RS-34821

Calculated chemistry of [ 75706-12-6 ]

Physicochemical Properties

Num. heavy atoms : 19
Num. arom. heavy atoms : 11
Fraction Csp3 : 0.17
Num. rotatable bonds : 4
Num. H-bond acceptors : 6.0
Num. H-bond donors : 1.0
Molar Refractivity : 60.69
TPSA : 55.13 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.18 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.33
Log Po/w (XLOGP3) : 2.49
Log Po/w (WLOGP) : 4.22
Log Po/w (MLOGP) : 2.14
Log Po/w (SILICOS-IT) : 2.97
Consensus Log Po/w : 2.83

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.25
Solubility : 0.153 mg/ml ; 0.000564 mol/l
Class : Soluble
Log S (Ali) : -3.29
Solubility : 0.138 mg/ml ; 0.00051 mol/l
Class : Soluble
Log S (SILICOS-IT) : -5.03
Solubility : 0.00252 mg/ml ; 0.00000933 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.45

Safety of [ 75706-12-6 ]

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

Application In Synthesis of [ 75706-12-6 ]

* 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 [ 75706-12-6 ]
  • Downstream synthetic route of [ 75706-12-6 ]

[ 75706-12-6 ] Synthesis Path-Upstream   1~12

  • 1
  • [ 67305-24-2 ]
  • [ 455-14-1 ]
  • [ 75706-12-6 ]
YieldReaction ConditionsOperation in experiment
86% With sodium hydrogencarbonate In N,N-dimethyl acetamide; toluene c)
4-Trifluoromethylaniline (5.75 g, 35.7 mm) was dissolved in a mixture of NaHCO3 (3.16 g, 37.6 mm), N,N-dimethylacetamide (0.7 ml, 7.5 mm) and toluene (70 ml).
The mixture was warmed to 40° C. and 5-methylisoxazole-4-carboxylic acid chloride (5 g, 34.4 mm) was added dropwise over 20 min.
The mixture was stirred at this temperature for another 3 h. and then it was heated to reflux temperature.
The hot mixture was washed with water (3*10 ml).
The organic phase was allowed to cool to ambient temperature, which induced leflunomide to precipitate as a white powder.
The powder was isolated by filtration and then dried at 60° C. to give leflunomide (8.0 g, 86percent) in 99.5percent purity.
Reference: [1] Farmaco, 1991, vol. 46, # 6, p. 789 - 802
[2] Patent: US2002/22646, 2002, A1,
[3] Chemistry - A European Journal, 2014, vol. 20, # 31, p. 9514 - 9518
[4] Patent: US2002/22646, 2002, A1,
[5] Patent: US5494911, 1996, A,
[6] Patent: US5504084, 1996, A,
[7] Patent: US5547971, 1996, A,
[8] Patent: US5519042, 1996, A,
[9] Patent: US4284786, 1981, A,
[10] Patent: WO2016/203410, 2016, A1, . Location in patent: Page/Page column 15; 16; 19
  • 2
  • [ 455-14-1 ]
  • [ 75706-12-6 ]
YieldReaction ConditionsOperation in experiment
62.34%
Stage #1: With thionyl chloride In toluene at 25 - 70℃; for 6 h;
Stage #2: at 0 - 30℃; for 6 h;
N-(4'-trifluoromethyIp)-5-methylisoxazole-4-carboxamide:5-Methylisoxazole~4-carboxylic acid 25.0 g (0.197 mol) was taken in toluene (312.5 ml), heated to reflux arid 62.5 ml toluene was distilled off. The solution was cooled to 25-30 0C. To this solution N, N-Dimethylformamide (0.16 ml) and thionyl chloride 25.68 g (0.216 mol) was added at 25-30 C and heated to 65 to 70 0C for 6 hours. Then the reaction mass was cooled to 0 0C and 4-trifluoromethylaniline 30.07 g (0.199 mol) was added drop wise at this temperature. The resulted reaction mixture was stirred at the same temperature for 2 hours, allowed to come to 25-30 0C and stirred for 4 hours. Water (125 ml) was added to the ' reaction mixture and stirred for 2 hours. The solid was separated out, which was filtered and washed with water (250 ml), dried under vacuum at 80 0C to obtain 40.25 g off white solid which was purified with toluene to give 33.15 g (62.34 percent) leflunomide with 99.9percent HPLC purity and any individual impurity less than 0.1percent.
Reference: [1] Patent: WO2007/86076, 2007, A2, . Location in patent: Page/Page column 5-7
  • 3
  • [ 455-14-1 ]
  • [ 67305-24-2 ]
  • [ 75706-12-6 ]
Reference: [1] Patent: US2002/22646, 2002, A1,
  • 4
  • [ 210627-03-5 ]
  • [ 75706-12-6 ]
Reference: [1] Journal of the American Chemical Society, 2013, vol. 135, # 23, p. 8436 - 8439
[2] Angewandte Chemie - International Edition, 2014, vol. 53, # 6, p. 1482 - 1484[3] Angew. Chem., 2014, vol. 126, # 6, p. 1506 - 1508
  • 5
  • [ 455-14-1 ]
  • [ 75706-12-6 ]
Reference: [1] Patent: US5547970, 1996, A,
  • 6
  • [ 42831-50-5 ]
  • [ 75706-12-6 ]
Reference: [1] Farmaco, 1991, vol. 46, # 6, p. 789 - 802
[2] Journal of the American Chemical Society, 2013, vol. 135, # 23, p. 8436 - 8439
[3] Chemistry - A European Journal, 2014, vol. 20, # 31, p. 9514 - 9518
[4] Patent: WO2016/203410, 2016, A1,
  • 7
  • [ 42831-50-5 ]
  • [ 90774-69-9 ]
  • [ 75706-12-6 ]
Reference: [1] Chemical Communications, 2012, vol. 48, # 96, p. 11781 - 11783
[2] Chemistry - A European Journal, 2015, vol. 21, # 36, p. 12787 - 12796
  • 8
  • [ 67305-24-2 ]
  • [ 75706-12-6 ]
Reference: [1] Journal of the American Chemical Society, 2013, vol. 135, # 23, p. 8436 - 8439
  • 9
  • [ 75706-11-5 ]
  • [ 75706-12-6 ]
Reference: [1] Green Chemistry, 2017, vol. 19, # 11, p. 2541 - 2545
  • 10
  • [ 351-87-1 ]
  • [ 75706-12-6 ]
Reference: [1] Green Chemistry, 2017, vol. 19, # 11, p. 2541 - 2545
  • 11
  • [ 1078-58-6 ]
  • [ 75706-12-6 ]
Reference: [1] Science, 2017, vol. 356, # 6344, p. 1272 - 1275
  • 12
  • [ 106-50-3 ]
  • [ 75706-12-6 ]
Reference: [1] Journal of the American Chemical Society, 2013, vol. 135, # 23, p. 8436 - 8439
Same Skeleton Products
Historical Records

Pharmaceutical Intermediates of
[ 75706-12-6 ]

Teriflunomide Related Intermediates

Chemical Structure| 455-24-3

[ 455-24-3 ]

4-(Trifluoromethyl)benzoic acid