Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 141743-49-9 | MDL No. : | MFCD07774189 |
Formula : | C6H4F2IN | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HCUZNQLIMDDCHF-UHFFFAOYSA-N |
M.W : | 255.00 | Pubchem ID : | 278943 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 43.48 |
TPSA : | 26.02 Ų |
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) : | -6.37 cm/s |
Log Po/w (iLOGP) : | 1.79 |
Log Po/w (XLOGP3) : | 2.09 |
Log Po/w (WLOGP) : | 3.0 |
Log Po/w (MLOGP) : | 3.26 |
Log Po/w (SILICOS-IT) : | 2.95 |
Consensus Log Po/w : | 2.62 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.18 |
Solubility : | 0.168 mg/ml ; 0.000658 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.27 |
Solubility : | 1.38 mg/ml ; 0.00541 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.55 |
Solubility : | 0.0717 mg/ml ; 0.000281 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 2.04 |
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: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With Iodine monochloride In acetic acid at 20℃; for 0.25 h; | 2, 6-Difluorobenzenamine (3. 0g, 22.56 mmoles) was dissolved in acetic acid (10 ml). Iodine monochloride (3.581g, 22.56 mmoles) was added to the solution. The mixture was stirred for 15 minutes at room temperature. After evaporation of the solvent, the residue was treated with an aqueous solution of sodium carbonate. The aqueous solution was extracted with dichloromethane. The organic extract was dried over MgS04 and was evaporated. Yield: 95percent of intermediate 33. |
95% | Stage #1: With Iodine monochloride; acetic acid In water at 20℃; for 0.25 h; Stage #2: With sodium carbonate In water |
Example A1; a) Preparation of intermediate 1; 2,6-difluorobenzeneamine (3.0g, 22.56 mmoles) was dissolved in acetic acid (10 ml).Iodine monochloride (3.58lg, 22.56 mmoles) was added to the solution. The mixturewas stirred for 15 minutes at room temperature. After evaporation of the solvent, theresidue was treated with an aqueous solution of sodium carbonate. The aqueoussolution was extracted with dichloromethane. The organic extract was dried overMgSCU and was evaporated. Yield : 95percent of intermediate 1. |
51% | With silver(I) nitrite; iodine In dichloromethane at 0 - 20℃; for 1 h; | Step 1: 4-Amino-3,5-difluoro-benzonitrile; To a suspension of iodine (5.59g, 22.0mmol) and AgNO2 (6.85g, 22.0mmol) in EPO <DP n="79"/>methylene chloride was added a solution of 2,6-difluoroaniline (2.58g, 20.0mmol) in methylene chloride at O0C, and the mixture was stirred for 30min at O0C and 30min at ambient temperature. The reaction was quenched with Na2S2O3. The reaction solution was extracted with methylenechloride, washed with water and brine, dried over anhyd. MgSO4, filtered and concentrated under reduced pressure. The obtained liquid was column-chromatographed (hexane/ethylacetate = 15/1) to yield a yellow solid (2.57mg, 51percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | for 2 h; Heating / reflux | A mixture of the solid and CuCN in DMF was heated with reflux for 2 days and then filtered through celite. The filtrate was dissolved in methylene chloride and water, and the aqueous phase was extracted with methylene chloride. The combined organic layer was washed with brine, dried over anhyd. MgSO4, filtered, and concentrated under reduced pressure. The crude residue was column-chromatographed (hexane/ethylacetate = 4/1) to yield a yellow solid (1.03g, 66percent).1HNMR (300MHz, CDC13): 7.15 (dd, 2H, J= 2.4 and 6.0 Hz), 4.28 (bs, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With Iodine monochloride; In acetic acid; at 20℃; for 0.25h; | 2, 6-Difluorobenzenamine (3. 0g, 22.56 mmoles) was dissolved in acetic acid (10 ml). Iodine monochloride (3.581g, 22.56 mmoles) was added to the solution. The mixture was stirred for 15 minutes at room temperature. After evaporation of the solvent, the residue was treated with an aqueous solution of sodium carbonate. The aqueous solution was extracted with dichloromethane. The organic extract was dried over MgS04 and was evaporated. Yield: 95% of intermediate 33. |
95% | Example A1; a) Preparation of intermediate 1; 2,6-difluorobenzeneamine (3.0g, 22.56 mmoles) was dissolved in acetic acid (10 ml).Iodine monochloride (3.58lg, 22.56 mmoles) was added to the solution. The mixturewas stirred for 15 minutes at room temperature. After evaporation of the solvent, theresidue was treated with an aqueous solution of sodium carbonate. The aqueoussolution was extracted with dichloromethane. The organic extract was dried overMgSCU and was evaporated. Yield : 95% of intermediate 1. | |
51% | With silver(I) nitrite; iodine; In dichloromethane; at 0 - 20℃; for 1h; | Step 1: 4-Amino-3,5-difluoro-benzonitrile; To a suspension of iodine (5.59g, 22.0mmol) and AgNO2 (6.85g, 22.0mmol) in EPO <DP n="79"/>methylene chloride was added a solution of 2,6-difluoroaniline (2.58g, 20.0mmol) in methylene chloride at O0C, and the mixture was stirred for 30min at O0C and 30min at ambient temperature. The reaction was quenched with Na2S2O3. The reaction solution was extracted with methylenechloride, washed with water and brine, dried over anhyd. MgSO4, filtered and concentrated under reduced pressure. The obtained liquid was column-chromatographed (hexane/ethylacetate = 15/1) to yield a yellow solid (2.57mg, 51%). |
With Iodine monochloride; In acetic acid; | Step 3: 60 g of 2,6-difluoroaniline was dissolved in 180 ml of acetic acid. A solution containing 75 g of iodine chloride dissolved in 48 ml of acetic acid was added dropwise therein, and then agitated at 80 C. for 2 hours. The reaction solution was poured into water, and the resulting deposited crystals were filtrated and washed with water. The crystals were recrystallized with methanol, vacuum distilled (125 C./22 mmHg), and recrystallized again with methanol to obtain 57 g of 2,6-difluoro-4-iodoaniline. | |
With pyridine; Iodine monochloride; In chloroform; water; acetic acid; | Step 3: 2,6-Difluoroaniline (38 g) was dissolved in acetic acid (120 ml), and then pyridine (25 g) was added thereto, followed by stirring. Then, a mixture of iodine monochloride (50 g) with acetic acid (30 ml) was added dropwise thereto. After stirring at room temperature for 1 hour, the reaction solution was further stirred at 70 to 80 C. for 2 hours. Then, the reaction solution was poured into water, and the precipitated crystals were filtered, followed by washing with water. The resulting crystals were dissolved in chloroform, and then washed with water twice, further with 10% potassium hydroxide aqueous solution twice, and furthermore with water twice, followed by distilling off chloroform. The residue was distilled under reduced pressure (b.p. 120 to 130 C./20 mmHg), and then recrystallized from methanol to give 4-iodo-2,6-difluoroaniline (44 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 3. Using the same method as Example 2, 2,6-difluoro-4-iodoaniline was obtained. | ||
Step 3: Using the same method as Example 2, 2,6-difluoro-4-iodoaniline was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; sodium hydrogencarbonate; acetic acid; sodium nitrite; In sulfuric acid; water; benzene; | Step 4: 12 g of sodium nitrite was dissolved in 91 ml of sulfuric acid and cooled to 10 C or less, and then 100 ml of acetic acid was added. At 20 to 25 C, 39 g of the <strong>[141743-49-9]2,6-difluoro-4-iodoaniline</strong> from Step 3 was added to the solution, and then the solution was agitated for one hour. A second solution was made by dissolving 37 g of copper sulfate pentahydrate in 91 ml of water to which was added 62 g of ice, and this solution was added to the first. A third solution containing 39 of potassium cyanide dissolved in 92 ml of water, 221 g of sodium bicarbonate, and 91 ml of benzene was added to the first solution, and a diazonium salt sulfuric acid solution was added therein. After agitation at room temperature for 3 hours, a sodium hydroxide aqueous solution was added to dissolve the crystals. After being extracted with chloroform, the crystals were washed three times alternating with a 10% sodium hydroxide solution and water. After distillation of the chloroform, the residue was extracted with hexane, and the hexane was distilled off. This residue was recrystallized with methanol to obtain 6.7 g of 1,3-difluoro-2-cyano-5-iodobenzene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; acetic acid; sodium nitrite;copper(I) bromide; In sulfuric acid; water; | Step 4: Sodium nitrite (17 g) was dissolved in sulfuric acid (130 ml), and then acetic acid (150 ml) was added thereto at 10 C. or lower. The mixed solution was kept at 20 to 25 C., and <strong>[141743-49-9]4-iodo-2,6-difluoroaniline</strong> (44 g) was added thereto for 1 hour, followed by stirring for 2 hours. The reaction solution was added dropwise to a mixed solution of copper(I) bromide (43 g) with 48% hydrobromic acid (125 ml), and stirred overnight. Then, water (1000 ml) was added to the solution, and the resulting solution was extracted with chloroform, followed by washing with water 3 times. After distilling off chloroform, the resultant was recrystallized from methanol to give 2-bromo-1,3-difluoro-4-iodobenzene (38 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | Example A9; a) Preparation of intermediate 22; A mixture of intermediate 18 (lequiv.), <strong>[141743-49-9]2,6-difluoro-4-iodo-benzeneamine</strong> (1.5 equiv.), and camphorsulfonic acid (0.7 equiv.) was refluxed for 20-48 hours in 2-propanol (oil bath 120C). The precipitate formed was collected by filtration and was successively washed on the filter with an aqueous solution of Na2C03, water, and dichloromethane, yielding intermediate 22. In order to increase the yield or to have analytical samples, the 2-propanol and CH2CI2 filtrate were combined and evaporated. The residue was suspended in an aqueous solution of Na2C03 and was extracted with CH2G2. After drying over MgSC>4 and evaporation of the dichloromethane extract, the residue was purified by column chromatography using 10% ethyl acetate in dichloromethane as eluent yielding intermediate 22. Total yield : 49% (CI-MS : 485 [M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | In N,N-dimethyl-formamide; for 2h;Heating / reflux; | A mixture of the solid and CuCN in DMF was heated with reflux for 2 days and then filtered through celite. The filtrate was dissolved in methylene chloride and water, and the aqueous phase was extracted with methylene chloride. The combined organic layer was washed with brine, dried over anhyd. MgSO4, filtered, and concentrated under reduced pressure. The crude residue was column-chromatographed (hexane/ethylacetate = 4/1) to yield a yellow solid (1.03g, 66%).1HNMR (300MHz, CDC13): 7.15 (dd, 2H, J= 2.4 and 6.0 Hz), 4.28 (bs, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In tetrahydrofuran; at 60℃; for 1h; | Step 1: 2,6-Difluoro-4-phenylethynyl-phenylamine Bis-(triphenylphosphine)-palladium(II)dichloride (826 mg, 1.18 mmol, 0.02 equiv.) was dissolved in 100 ml THF. 2,6-Difluoro-4-iodoaniline (15 g, 58.8 mmol) and phenylacetylene (7.2 g, 7.8 ml, 70.6 mmol, 1.2 equiv.) were added at room temperature. Triethylamine (29.8 g, 41 ml, 0.29 mol, 5 equiv.), triphenylphosphine (617 mg, 2.35 mmol, 0.04 equiv.) and copper(I)iodide (112 mg, 0.58 mmol, 0.01 equiv.) were added and the mixture was stirred for 1 hour at 60C. The reaction mixture was cooled and extracted with saturated NaHC03 solution and two times with ethyl acetate. The organic layers were washed three times with water, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with an ethyl acetate:heptane gradient 0: 100 to 40:60. The desired 2,6- difluoro-4-phenylethynyl-phenylamine (12.6 g, 93 % yield) was obtained as a yellow solid, MS: m/e = 230.1 (M+H+). |
93% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In tetrahydrofuran; at 60℃; for 1h; | Bis-(triphenylphosphine)-palladium(II)dichloride (826 mg, 1.18 mmol, 0.02 equiv.) was dissolved in 100 ml THF. 2,6-Difluoro-4-iodoaniline (15 g, 58.8 mmol) and phenylacetylene (7.2 g, 7.8 ml, 70.6 mmol, 1.2 equiv.) were added at room temperature. Triethylamine (29.8 g, 41 ml, 0.29 mol, 5 equiv.), triphenylphosphine (617 mg, 2.35 mmol, 0.04 equiv.) and copper(I)iodide (112 mg, 0.58 mmol, 0.01 equiv.) were added and the mixture was stirred for 1 hour at 60C. The reaction mixture was cooled and extracted with saturated NaHC03 solution and two times with ethyl acetate. The organic layers were washed three times with water, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with an ethyl acetate:heptane 0: 100 to 40:60 gradient. The desired 2,6- difluoro-4-phenylethynyl-phenylamine (12.6 g, 93 % yield) was obtained as a yellow solid, MS: m/e = 230.1 (M+H+). |
93% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In tetrahydrofuran; at 60℃; for 1h; | Bis-(triphenylphosphine)-palladium(II)dichloride (826 mg, 1.18 mmol, 0.02 equiv.) was dissolved in 100 ml THF. 2,6-Difluoro-4-iodoaniline (15 g, 58.8 mmol) and phenylacetylene (7.2 g, 7.8 ml, 70.6 mmol, 1.2 equiv.) were added at room temperature. Triethylamine (29.8 g, 41 ml, 0.29 mol, 5 equiv.), triphenylphosphine (617 mg, 2.35 mmol, 0.04 equiv.) and copper(I)iodide(112 mg, 0.58 mmol, 0.01 equiv.) were added and the mixture was stuffed for 1 hour at 60C. The reaction mixture was cooled and extracted with saturated NaHCO3 solution and two times with ethyl acetate. The organic layers were washed three times with water, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on asilica gel column eluting with an ethyl acetate:heptane 0:100 to 40:60 gradient. The desired 2,6- difluoro-4-phenylethynyl-phenylamine (12.6 g, 93 % yield) was obtained as a yellow solid, MS:mle = 230.1 (M+Hj. |
93% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In tetrahydrofuran; at 60℃; for 1h; | Example 1 (8S)-3'-[2,6-Difluoro-4-(2-phenylethynyl)phenyl]-l'-methyl-spiro[6,7-dihydro-5H- isoquinoline-8 6'-hexahydropyrimidine]-2',4'-dione Step 1: 2,6-Difluoro-4-phenylethvnyl-phenylamine Bis-(triphenylphosphine)-palladium(II)dichloride (826 mg, 1.18 mmol, 0.02 equiv.) was dissolved in 100 ml THF. 2,6-Difluoro-4-iodoaniline (15 g, 58.8 mmol) and phenylacetylene (7.2 g, 7.8 ml, 70.6 mmol, 1.2 equiv.) were added at room temperature. Triethylamine (29.8 g, 41 ml, 0.29 mol, 5 equiv.), triphenylphosphine (617 mg, 2.35 mmol, 0.04 equiv.) and copper(I)iodide (112 mg, 0.58 mmol, 0.01 equiv.) were added and the mixture was stirred for 1 hour at 60C. The reaction mixture was cooled and extracted with saturated NaHC03 solution and two times with ethyl acetate. The organic layers were washed three times with water, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with an ethyl acetate:heptane 0: 100 to 40:60 gradient. The desired 2,6- difluoro-4-phenylethynyl-phenylamine (12.6 g, 93 % yield) was obtained as a yellow solid, MS: m/e = 230.1 (M+H+). |
93% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In tetrahydrofuran; at 60℃; for 1h; | Bis-(triphenylphosphine)-palladium(II)dichloride (826 mg, 1.18 mmol, 0.02 equiv.) was dissolved in 100 ml THF. 2,6-Difluoro-4-iodoaniline (15 g, 58.8 mmol) and phenylacetylene (7.2 g, 7.8 ml, 70.6 mmol, 1.2 equiv.) were added at room temperature. Triethylamine (29.8 g, 41 ml, 0.29 mol, 5 equiv.), triphenylphosphine (617 mg,2.35 mmol, 0.04 equiv.) and copper(I)iodide (112 mg,0.58 mmol, 0.01 equiv.) were added and the mixture was stirred for 1 hour at 60 C. The reaction mixture was cooled and extracted with saturated NaHCO3 solution and two times with ethyl acetate. The organic layers were washed three times with water, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with an ethyl acetate:heptane gradient 0:100 to 40:60. The desired 2,6-difluoro-4-phenylethynyl-phenylamine (12.6 g, 93% yield) was obtained as a yellow solid, MS:mle=230.1 (M+Hj. |
93% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine; In tetrahydrofuran; at 60℃; for 1h; | Bis-(triphenylphosphine)-palladium(II)dichloride (826 mg, 1.18 mmol, 0.02 equiv.) was dissolved in 100 ml THF. 2,6-Difluoro-4-iodoaniline (15 g, 58.8 mmol) and phenylacetylene (7.2 g, 7.8 ml, 70.6 mmol, 1.2 equiv.) were added at room temperature. Triethylamine (29.8 g, 41 ml, 0.29 mol, 5 equiv.), triphenylphosphine (617 mg, 2.35 mmol, 0.04 equiv.) and copper(I)iodide (112 mg, 0.58 mmol, 0.01 equiv.) were added and the mixture was stirred for 1 hour at 60C. The reaction mixture was cooled and extracted with saturated NaHCO3 solution and two times with ethyl acetate. The organic layers were washed three times with water, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with an ethyl acetate:heptane gradient 0:100 to 40:60. The desired 2,6- difluoro-4-phenylethynyl-phenylamine (12.6 g, 93 % yield) was obtained as a yellow solid, MS: mle = 230.1 (M+Hj |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 60℃; for 16h; | 2,6-Difluoro-4-iodoaniline (10 g, 39.2 mmol) was dissolved in 100 ml of THF. Hunig?s base(7.53 ml, 5.58 g, 43.1 mmol, 1.1 equiv.) and phenyl chloroformate (5.4 ml, 6.75 g, 43.1 mmol,1.1 equiv.) were added at room temperature and the mixture was stuffed for 16 hours at 60C.The reaction mixture was extracted with saturated NaHCO3 solution and two times with ethylacetate. The organic layers were washed with water and brine, dried over sodium sulfate andevaporated to dryness. The residue was stuffed in heptane, filtered off and dried for 2 hours at 50C and <10 mbar. The desired phenyl (2,6-difluoro-4-iodophenyl)carbamate (10.3 g, 70 % yield) was obtained as a light brown solid, MS: mle = 376.0 (M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The title compound isolated as a byproduct was obtained as a light yellow oil, MS: mle =463.1/465.1 (M+Hj, using chemistry similar to that described in Example 1, step 5 by usingtriphosgene in toluene instead of CDI in DMF starting from 2-chloro-4-iodoaniline and methyl(35)-3-amino-3- [1- (2-trimethylsilylethoxymethyl)pyrazol-4-yl]butanoate (Example 16, step 2).2,6-Difluoro-4-phenylethynyl-phenylamine (Example], step]) (170 mg, 0.75 mmol, 1.5 equiv.) was dissolved in DMF (2.0 ml) and CDI (121 mg, 0.75 mmol, 1.5 equiv.) was added at roomtemperature. The mixture was stined for 1 hour at 100 C. To the mixture methyl (35)-3-amino-3-thiazol-2-yl-butanoate (Example], step 4) (100 mg, 0.50 mmol, 1.0 equiv.) was added and stined for 1 hour at room temperature. The reaction mixture was evaporated with isolute. The crude product was purified by flash chromatography eluting with an ethyl acetate:heptane 0:100 to 100:0 gradient. The desired methyl (35)-3-[[2,6-difluoro-4-(2-phenylethynyl)phenyl]carbamoylamino]-3-thiazol-2-yl-butanoate (155 mg, 68 % yield) was obtained as a light yellow solid, MS: mle = 456.2 (M+H |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With caesium carbonate; methyl iodide; In N,N-dimethyl-formamide; at 20℃; for 1h; | The title compound was obtained as a light brown solid, MS: mle = 577.1 (M+Hj, usingchemistry similar to that described in Example 1, step 5, 6 and 7 starting from <strong>[141743-49-9]2,6-difluoro-4-iodoaniline</strong> and methyl (35)-3-amino-3- [1 -(2-trimethylsilylethoxymethyl)pyrazol-4-yl]butanoate(Example 16, step 2).(122 mg, 0.29 mmol) (6S )-3- [2,6-Difluoro-4- (2-phenylethynyl)phenyl] -6-methyl-6-thiazol-2-yl-hexahydropyrimidine-2,4-dione (Example], step 7) was dissolved in DMF (2 ml) and cesiumcarbonate (141 mg, 0.43 mmol, 1.5 equiv.) and iodomethane (49 mg, 22 ul, 0.35 mmol, 1.2 equiv.) were added at room temperature. The mixture was stirred for 1 hour at room temperature. The reaction mixture was evaporated with isolute. The crude product was purified by flash chromatography on a silica gel column eluting with an ethyl acetate:heptane 0:100 to 100:0gradient.The desired (65)-3- [2,6-difluoro-4- (2-phenylethynyl)phenyl] -1 ,6-dimethyl-6-thiazol-2- yl-hexahydropyrimidine-2,4-dione (95 mg, 76 % yield) was obtained as a colorless oil, MS: mle = 438.2 (M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | To a solution of 2,6-difluoro-4-iodo-phenyl amine (3.00 g, 1 1.8mmol) in toluene (80m1) was added CDI (5.72g, 35.3mmol) and reaction mixture was stirred for lh at 110C. Then (2-methyl- 3-oxo-piperazin-2-yl)-acetic acid methyl ester (2.63g, 14.lmmol) was added and reaction mixture was refluxed for 2h. Reaction mixture was concentrated and resulting crude was purified by column chromatography over silica gel (70% EA/hexane) to obtain the title compound (4.37g, 85%) as an off-white solid, MS: mle = 436.2 (M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With bis-triphenylphosphine-palladium(II) chloride; tetrabutylammomium bromide; potassium carbonate; In ethanol; water; toluene; for 4h;Inert atmosphere; Reflux; | Under nitrogen, 5-pentylthieno [3,2-b] thiophene-2-boronic acid (6.0 g, 0.0236 mol), <strong>[141743-49-9]2,6-difluoro-4-iodoaniline</strong> (5.1 g, 0.02 mol), potassium carbonate (8.3 g, 0.06 mol),Tetrabutylammonium bromide (0.64 g, 0.002 mol), toluene 40 mL, ethanol 40 mL, water 40 mL,Mix evenly, add bistriphenylphosphine palladium dichloride(0.42 g, 0.6 mmol) and refluxed for 4 h to monitor the reaction. After completion of the reaction, the reaction solution was extracted twice with toluene, the organic phases were combined, washed with water to neutral, dried under reduced pressure, and recrystallized from a mixed solvent of n-heptane and toluene to give 4.2 g of an off-white solid,GC purity 98.8%, yield 62%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With tetrabutylammomium bromide; triethylamine; zinc(II) oxide; In dimethyl sulfoxide; at 100℃; for 22h;Inert atmosphere; | PdCI2(MeCN)2 (101.7 mg, 0.39 mmol) was added to a mixture of <strong>[141743-49-9]2,6-difluoro-4-iodoaniline</strong>(2.Og, 7.84mmol),ZnO(830mg, 10.2mmol), Bu4NBr(3.79g, 11.8mmol), Et3N (372 pL,2.67 mmol) and DMSO (20 mL). The mixture was stirred at 100 00 for 16 h (not protectedfrom air). Et3N (47.4 pL, 0.34 mmol) was added and the mixture stirred for 6 h, cooled tort, diluted with Et20 and washed with H20. The aq layer was extracted with Et20 and thecombined extracts were washed with brine, dried over Na2SO4 and concentrated.Purification by chromatography gave the sub-title compound (270 mg, 1.58 mmol, 20 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | 2,6-Difluoro-4-iodoaniline (14.4 g, 56.56 mmol, 1.2 equiv.) was dissolved in DMF (250 ml) and CDI (9.17 g, 56.56 mmol, 1.2 equiv.) was added at room temperature. The mixture was stirred for 1 hour at 100 C. To the mixture methyl 2-[(45)-4-amino-1-(2-trimethylsilylethoxymethyl)- 6,7-dihydro-SH-indazol-4-yllacetate (Example], step 4) (16 g, 47.13 mmol, 1.0 equiv.) dissolved in 20 ml of DMF was added at room temperature and the mixture was stirred for 2 hours at room temperature. The reaction mixture was poured into water and extracted three times with ethyl acetate. The organic layers were washed with water and brine, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography. The desired methyl 2- [(45)-4- [(2,6-difluoro-4-iodo-phenyl)carbamoylaminol -1 -(2- trimethylsilylethoxymethyl)-6,7-dihydro-SH-indazol-4-yll acetate (9.1 g, 19 % yield) was obtained as a brown gum, MS: mle = 621.1 (M+H+] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine; In N,N-dimethyl-formamide; at 80℃; for 12h;Inert atmosphere; | Step A: Methyl acrylate (25.32g, 294.10mmol, 26.38mL, 5.00eq), triethylamine (11.90g, 117.64mmol, 16.30mL,2.00eq) and 1,1?-bis(diphenylphosphino)ferrocene palladium chloride (2.15g, 2.94mmol, 0.05eq) were added to a solutionof <strong>[141743-49-9]2,6-difluoro-4-iodoaniline</strong> (15.00g, 58.82mmol, 1.00eq) in 100 mL N,N-dimethylformamide. The reaction solution wasstirred at 80C under nitrogen atmosphere for 12 hours. Then 400mL ethyl acetate was added, and the mixture wasfiltered through celite. The filtrate was washed three times with 400mL water. The organic phase was dried over anhydroussodium sulfate, filtered and concentrated to give a crude product, which was purified by silica gel column chromatographyto give intermediate 108 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
270 mg | With tetrabutylammomium bromide; triethylamine; zinc(II) oxide; In dimethyl sulfoxide; at 100℃; for 22h; | PdCI2(MeCN)2 (101.7 mg, 0.39 mmol) was added to a mixture of <strong>[141743-49-9]2,6-difluoro-4-iodoaniline</strong>(2.0 g, 7.84 mmol), ZnO (830 mg, 10.2 mmol), Bu4NBr (3.79 g, 11.8 mmol), Et3N (372 pL,2.67 mmol) and DMSO (20 mL). The mixture was stirred at 100 00 for 16 h (not protectedfrom air). Et3N (47.4 pL, 0.34 mmol) was added and the mixture stirred for 6 h, cooled tort, diluted with Et20 and washed with H20. The aq layer was extracted with Et20 and thecombined extracts were washed with brine, dried over Na2SO4 and concentrated.Purification by chromatography gave the sub-title compound (270 mg, 1.58 mmol, 20 %). |
Tags: 141743-49-9 synthesis path| 141743-49-9 SDS| 141743-49-9 COA| 141743-49-9 purity| 141743-49-9 application| 141743-49-9 NMR| 141743-49-9 COA| 141743-49-9 structure
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :