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[ CAS No. 1289942-66-0 ] {[proInfo.proName]}

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Chemical Structure| 1289942-66-0
Chemical Structure| 1289942-66-0
Structure of 1289942-66-0 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1289942-66-0 ]

CAS No. :1289942-66-0 MDL No. :MFCD22581651
Formula : C12H15FN2O3 Boiling Point : -
Linear Structure Formula :- InChI Key :IAAHEGARPMZSTJ-UHFFFAOYSA-N
M.W : 254.26 Pubchem ID :67106897
Synonyms :

Calculated chemistry of [ 1289942-66-0 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 18
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.33
Num. rotatable bonds : 5
Num. H-bond acceptors : 4.0
Num. H-bond donors : 3.0
Molar Refractivity : 64.93
TPSA : 78.43 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) : -6.81 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.87
Log Po/w (XLOGP3) : 1.47
Log Po/w (WLOGP) : 1.69
Log Po/w (MLOGP) : -0.66
Log Po/w (SILICOS-IT) : 1.27
Consensus Log Po/w : 1.13

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -2.26
Solubility : 1.4 mg/ml ; 0.00551 mol/l
Class : Soluble
Log S (Ali) : -2.72
Solubility : 0.48 mg/ml ; 0.00189 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.32
Solubility : 0.122 mg/ml ; 0.000481 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 1.78

Safety of [ 1289942-66-0 ]

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 [ 1289942-66-0 ]

* 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 [ 1289942-66-0 ]
  • Downstream synthetic route of [ 1289942-66-0 ]

[ 1289942-66-0 ] Synthesis Path-Upstream   1~8

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YieldReaction ConditionsOperation in experiment
87% With water; potassium carbonate; <i>L</i>-proline; copper(l) chloride In N,N-dimethyl-formamide at 100℃; for 24 h; Inert atmosphere 4-bromo-2-fluoro -N- methylbenzamide, 2-amino - isobutyric acid molar ratio, catalyst, co-catalyst, acid binding agent, followed by water 1:1.5:0.1:0.1:4:2.3
In a single-neck flask was added4-bromo-2-fluoro -N- methylbenzamide (10g, 43.1mmol), 2- amino - isobutyric acid (6.7g, 64.7mmol), potassium carbonate (23.8g, 172.4mmol), proline (0.7g, 4.31mmol), water (1.8ml, 100mmol) was dissolved in DMF (60ml), andStirring under nitrogen replacementAfter addition of CuCl (0.45g, 4.31mmol), was heated to 100 , reaction 24h.After completion of the reaction first added water (120ml) the mixture was diluted, added and extracted with dichloromethane, the organic phase was removed, the aqueous phase was adjusted pH = 4 with 1mol / L citric acid solution, and the precipitated solid was filtered. The solid washed with water and ethanol (100: 1) mixed solution was washed three times to give pure white solid 9.5g. Yield 87percent
75.4%
Stage #1: With potassium carbonate In water; N,N-dimethyl-formamide at 30℃;
Stage #2: With 2-acetylcyclohexanone In water; N,N-dimethyl-formamide at 105℃; Inert atmosphere
Stage #3: With citric acid In Isopropyl acetate; water
The bromobenzamide A-2 (10 g, 43.1 mmol), aminoisobutyric acid B-l (6.7 g, 64.6 mmol, 1.5 equiv), K2C03 (15 g, 2.5 equiv), 99percent CuCl (0.8 g, 8.1 mmol, 0.2 equiv), DMF (60 mL, 6 vol) and water (1.8 mL) were added to the flask and the reaction slurry was heated to 30 °C. 2-Acetylcyclohexanone (1.14 mL, 8.1 mmol, 0.2 equiv) was added to the reaction slurry followed by stirring at 105 °C under nitrogen for 12-14 h. HPLC analysis showed 96.6percent conversion to the desired product. The reaction mixture was then cooled to RT and extracted with water (120 mL) and IP Ac (60 mL). The lower aqueous layer was re-extracted with IP Ac (60 mL) and acidified with 180 mL of 1M citric acid to a pH of 4.0. The product began to crystallize at RT and the batch was further cooled to 5-7 °C, filtered, washed with water (40 mL) and dried under vacuum at 50 °C for 12 h. The reaction yielded 8.3 g of product C-1 (75.4percent yield) as a tan solid with HPLC purity of 99.6percent.
26 g
Stage #1: With potassium carbonate In 1,4-dioxane; water; N,N-dimethyl-formamide for 0.333333 h; Inert atmosphere
Stage #2: With <i>L</i>-proline; copper(l) chloride In 1,4-dioxane; water; N,N-dimethyl-formamide for 24.33 h; Inert atmosphere; Reflux
4-bromo-2-fluoro-N-methyl benzamide (48.0 gm, 0.21mol) and K2C03 (52.8 gm, 0.38 mol) was charged in to reaction flask containing DMF (67.2 mL), 1,4-dioxane (268mL) and DM water (8.6mL). The reaction mixture was purged with nitrogen gas for 20 min and then charged CuCl (6.24 gm, 0.06 mol),L-proline(9.6 gm, 0.08 mol) and 2-aminoisobutyric acid (31.6 gm, 0.31mol). Continue purging nitrogen gas for 20 min followed by refluxed for 24 hrs. Solvent is distilled off completely from the obtained reaction mixture under vacuum at 70°C. The reaction mass was cooled to 10 to 15 °C and then charged DM water (20 mL). The pH of the reaction mass adjusted to 3-5 with 1 M citric acid solution to obtain the title product. Yield: 26.0 gm Chromatographic Purity (By HPLC): 95.38 percent
Reference: [1] Patent: CN105330560, 2016, A, . Location in patent: Paragraph 0023; 0024; 0025; 0026; 0027
[2] Patent: WO2011/106570, 2011, A1, . Location in patent: Page/Page column 44
[3] Patent: WO2016/5875, 2016, A1, . Location in patent: Page/Page column 15
[4] Patent: CN104016924, 2016, B, . Location in patent: Paragraph 0017; 0026-0028
  • 2
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YieldReaction ConditionsOperation in experiment
53%
Stage #1: With triethylamine In N,N-dimethyl acetamide at 70℃; for 1 h;
Stage #2: at 100℃; for 1.66667 h;
50.0 g (0.244 mol) of 4-amino-2-fluoro-N-methylbenzamide hydrochloride of formula V was charged into a 500-ml vessel equipped with an anchor agitator, 50 ml of dimethylacetamide was added and the mixture was heated up to 70°C. Then, 68.0 g (0.672 mol) of triethylamine was added and the mixture was stirred for 60 min. After that the temperature was increased to 100°C and a pre-heated solution of 54.3 g (0.325 mol) of 2-bromo-2-methylpropionic acid in 25 ml of dimethylacetamide was added dropwise to the mixture during 10 min. The mixture was agitated at 100°C for another 1 h, then it was cooled down to 40°C and 125 ml of water and a solution of 40 g of citric acid in 100 ml of water were added. The mixture was seeded with the product, cooled down to 20°C and stirred overnight. The separated product was aspirated on a Biichner funnel, washed with a sizeable amount of water and dried in a vacuum drier overnight. 33,2 g (53percent by weight) of the product of formula XI was obtained in the form of pinkish crystals, melt point 205 to 210°C. HPLC purity: 97.46percent. 1H NMR (DMSO): 6(ppm): 1.45 (s, 6H), 2.73 (d, 3H), 6.16 (dd, 1H), 6.35 (dds 1H), 6.70 (b, 1H), 7.46 (t, 1H), 7.65 (t, 1H), 12.7 (b, 1H)
Reference: [1] Patent: WO2015/154730, 2015, A1, . Location in patent: Page/Page column 8; 9
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YieldReaction ConditionsOperation in experiment
12 g With triethylamine In dichloromethane at 20 - 30℃; for 15 h; Inert atmosphere In a 500 mL four necked round bottomed flask equipped with nitrogen atmosphere facility, mechanical stirrer, thermometer and an addition funnel, (10 g) 4-amino-2-fluoro-N-methylbenzamide, (16 g) bromo-isobutyric acid and 100 mL dichloromethane were added at room temperature. (25 mL) triethylamine was added and the reaction mixture was stirred for 15 hours at 20-30° C. After completion of reaction, the reaction mixture was concentrated completely UN at 40° C. 100 mL water was added and stirred for 1 hour. 7.5 mL hydrochloric acid was added and stirred for 30 min. The reaction mixture was cooled to 0-5° C. and stirred for 1 hour, filtered, washed with 25 mL water and dried to obtain 15.2 g titled compound with 94.97percent purity by HPLC In a 500 mL four necked round bottomed flask equipped with nitrogen atmosphere facility, mechanical stirrer, thermometer and an addition funnel, (15 g) 2-((3-fluoro-4-(methylcarbamoyl)phenyl)amino)-2-methylpropanoic acid obtained in example-1 and 120 mL acetone were heated to 55 to 60° C. for 1 hour. The reaction mixture was cooled to 0 to 5° C. and the product thus obtained was filtered and dried under vacuum at 50° C. to obtain 12 g titled compound with 99.54percent purity by HPLC.
Reference: [1] Archiv der Pharmazie, 2018, vol. 351, # 11,
[2] Patent: US2015/210649, 2015, A1, . Location in patent: Paragraph 0084; 0085
[3] Patent: US2017/158643, 2017, A1, . Location in patent: Paragraph 0117
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Reference: [1] Patent: WO2011/106570, 2011, A1,
[2] Patent: WO2016/5875, 2016, A1,
[3] Patent: CN104016924, 2016, B,
  • 5
  • [ 151982-51-3 ]
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Reference: [1] Patent: WO2011/106570, 2011, A1,
[2] Patent: CN104016924, 2016, B,
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Reference: [1] Patent: WO2015/154730, 2015, A1,
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Reference: [1] Patent: WO2015/154730, 2015, A1,
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  • [ 1289942-66-0 ]
Reference: [1] Patent: WO2015/154730, 2015, A1,
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