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CAS No. : | 117832-17-4 | MDL No. : | MFCD07779006 |
Formula : | C8H10IN | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ZAVYUORHSOSKGS-UHFFFAOYSA-N |
M.W : | 247.08 g/mol | Pubchem ID : | 14040291 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.25 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 53.5 |
TPSA : | 26.02 Ų |
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) : | -5.99 cm/s |
Log Po/w (iLOGP) : | 2.1 |
Log Po/w (XLOGP3) : | 2.56 |
Log Po/w (WLOGP) : | 2.5 |
Log Po/w (MLOGP) : | 3.03 |
Log Po/w (SILICOS-IT) : | 2.99 |
Consensus Log Po/w : | 2.63 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.43 |
Solubility : | 0.0921 mg/ml ; 0.000373 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.75 |
Solubility : | 0.435 mg/ml ; 0.00176 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.77 |
Solubility : | 0.0421 mg/ml ; 0.00017 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.52 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
GHS Pictogram: |
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* 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 |
---|---|---|
93% | With 1-butyl-3-methyl-pyridinium dichloroiodate; at 80℃; for 1h;Inert atmosphere; | 3,4-Dimethylaniline (0.1 g, 0.82mmol) and l-butyl-3-methylpyridinium dichloroiodate (BMPDCI) (0.344 g, 0.99 mmol) were added in 10 ml one necked round bottomed flask in an inert atmosphere. The reaction mixture was heated at 80 C for lhr. The reaction was monitored by TLC. After the reaction was completed (TLC), ethyl acetate (10ml) was added followed by addition of water (10ml). The entire reaction mixture was extracted with ethyl acetate (3x10ml). The combined ethyl acetate layer was washed with water, brine and dried over anhydrous sodium sulphate. The separated combined organic layers, was evaporated under vacuum, to afford the crude product. This crude product was purified by silica gel column chromatography to afford pure 2-iodo-4,5-dimethylaniline in 0.19 g, (93% yield). 1H NMR (CDCI3 delta/ppm): 7.31 (s, 1H), 6.49 (s, 1H), 3.79 (broad singlet, 2H, NH2), 2.12-2.14 (d, 6H, Ar-CH3). |
85% | With iodine; sodium hydrogencarbonate; In methanol; water; at 20℃; for 1h;Inert atmosphere; | [Example 496] Compound dd47 2-Iodo-4,5-dimethylaniline [1071] Iodine (2.06 g, 8.11 mmol) was added in 10 parts to a mixed solution of 3,4-dimethylaniline (893 mg, 7.37 mmol) and sodium bicarbonate (683 mg, 8.14 mmol) in MeOH/ water (7 ml/7 ml), and it was stirred at room temperature for one hour under a nitrogen atmosphere. Followed by addition of water to the reaction mixture and extraction with dichloromethane, the organic layer was then washed with a saturated aqueous solution of sodium thiosulfate and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, followed by concentration under reduced pressure. The resultant residue was purified by silica gel column chromatography (ethyl acetate/hexane) to yield the title compound (1.54 g, 85%) as a brown solid. LCMS: m/z 248 [M+H]+ HPLC retention time: 1.91 min (analysis condition D) |
85% | With iodine; sodium hydrogencarbonate; In methanol; water; at 20 - 25℃; for 1h;Inert atmosphere; | Iodine (2.06 g, 8.11 mmol) was added in 10 parts to a mixed solution of 3,4-dimethylaniline (893 mg, 7.37 mmol) and sodium bicarbonate (683 mg, 8.14 mmol) in MeOH/water (7 ml/7 ml), and it was stirred at room temperature for one hour under nitrogen atmosphere. Followed by addition of water to the reaction mixture and extraction with dichloromethane, the organic layer was then washed with a saturated aqueous solution of sodium thiosulfate and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, followed by concentration under reduced pressure. The resultant residue was purified by silica gel column chromatography (ethyl acetate/n-hexane) to yield the title compound (1.54 g, 85%) as a brown solid. LCMS: m/z 248 [M+H]+ HPLC retention time: 1.91 min (analysis condition C) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With copper(II) oxide; potassium hydroxide; In dimethyl sulfoxide; at 110℃; for 6h; | General procedure: A mixture of 2-iodoaniline (0.5 mmol), CS2 (0.6 mmol), an amine (0.6 mmol), CuO nanoparticles (0.5 mmol), and KOH (1.5-2 mmol) in DMSO (3 mL) was stirred at 110 C for 6 h. The cooled solution was partitioned between ethyl acetate and water, and the organic layer was washed with water and brine, and then dried over Na2SO4. After removal of the solvent in vacuo, the residue was purified by silica-gel chromatography to give the desired benzothiazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 20℃; for 1h;Inert atmosphere; | General experimental procedure: o-iodoaniline (1.0 mmol) and phenyl isothiocyanate (1.2 mmol) was mixtured and stirred for 1 h at room temperature (Method A), or o-iodoaniline (1.0 mmol) and phenyl isothiocyanate (1.2 equiv) was mixtured and stirred for 1 h at melting point temperature of phenyl isothiocyanate (Method B), or o-halobenzothioureas (1.0 mmol) (Method C), then anhydrous DMSO (5 ml) and base (3.0 mmol) was added, the stirring continued for about 5-10 h at 130 C (TLC monitor). After the reaction was completed, the reaction mixture was cooled to room temperature and ice-water was added, then the mixture was extracted with EtOAc. The combined organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under vacuum and then the residue was purified by column chromatography (eluent: petroleum ether/ethyl acetate (5:1 to 7:1)) on silica gel to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
for 1h;Inert atmosphere; Heating; | General experimental procedure: o-iodoaniline (1.0 mmol) and phenyl isothiocyanate (1.2 mmol) was mixtured and stirred for 1 h at room temperature (Method A), or o-iodoaniline (1.0 mmol) and phenyl isothiocyanate (1.2 equiv) was mixtured and stirred for 1 h at melting point temperature of phenyl isothiocyanate (Method B), or o-halobenzothioureas (1.0 mmol) (Method C), then anhydrous DMSO (5 ml) and base (3.0 mmol) was added, the stirring continued for about 5-10 h at 130 C (TLC monitor). After the reaction was completed, the reaction mixture was cooled to room temperature and ice-water was added, then the mixture was extracted with EtOAc. The combined organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under vacuum and then the residue was purified by column chromatography (eluent: petroleum ether/ethyl acetate (5:1 to 7:1)) on silica gel to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60.8 g of lithium chloride is added to a solution of 15.5 g of [1,4]-benzoquinone in 350 ml of THF, and it is degassed with nitrogen. 3.2 g of palladium acetate and 23.7 g of benzyl acrylate are added and it is degassed with nitrogen for about 30 minutes. Than a solution of 35.1 g of <strong>[117832-17-4]2-iodo-4,5-dimethylaniline</strong> (prepared according to J. Med. Chem. 2001, 44, 3856-3871) in 150 ml of THF is added and it is stirred overnight. It is filtered and the filtrate is evaporated. The solid residue thus obtained is triturated with ether. It is filtered, the filtrate is washed with a solution of NaOH 0.5N and then with water and with brine. It is evaporated and then the solid residue is purified by silica gel chromatography, eluting with a cyclohexane/EtOAc mixture (8/2; v/v). 57.6 g of the expected compound is obtained in the form of a white powder.1H NMR: DMSO-d6 (250 MHz): delta (ppm): 2.14 (3H, s); 2.19 (3H, s); 4.93 (1H, d); 5.18 (2H, s); 7.23 (1H, s); 7.30-7.45 (5H, m); 7.59 (1H, s); 7.72 (1H, dd); 10.05 (1H, d). | ||
With p-benzoquinone; lithium chloride;palladium diacetate; In tetrahydrofuran;Inert atmosphere; | Preparation 2.65,6-Dimethyl-1 /-/-indole-3-carboxylic acid.(VIII): X = CH; R4 = Me; R5 = Me.Step 1 : 3-[(2-lodo-4,5-dimethylphenyl)amino]benzyl acrylate (XVIII).60.8 g of lithium chloride is added to a solution of 15.5 g of [1 ,4]- benzoquinone in 350 ml of THF, and it is degassed with nitrogen. 3.2 g of palladium acetate and 23.7 g of benzyl acrylate are added and it is degassed with nitrogen for about 30 minutes. Then a solution of 35.1 g of 2-iodo-4,5- dimethylaniline (prepared according to J. Med. Chem 2001 , 44, 3856-3871 ) in 150 ml of THF is added and it is stirred overnight. It is filtered and the filtrate is evaporated. The solid residue thus obtained is triturated with ether. It is filtered, the filtrate is washed with a solution of NaOH 0.5N and then with water and with brine. It is evaporated and then the solid residue is purified by silica gel chromatography, eluting with a cyclohexane/EtOAc mixture (8/2; v/v). 57.6 g of the expected compound is obtained in the form of a white powder.1H NMR: DMSO-de (250 MHz): delta (ppm): 2.14 (3H, s); 2.19 (3H, s); 4.93 (1 H, d); 5.18 (2H, s); 7.23 (1 H, s); 7.30-7.45 (5H, m); 7.59 (1 H, s); 7.72 (1 H, dd); 10.05 (1 H, d). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With copper(l) iodide; sodium azide; potassium carbonate; N,N`-dimethylethylenediamine; In dimethyl sulfoxide; at 80℃; for 20h;Sealed tube; | General procedure: 2-iodoaniline (54.8 mg, 0.25 mmol) 1a, sodium azide (19.5 mg, 0.3mmol) 3, CuI (4.8 mg, 0.025 mmol), K2CO3 (34.5 mg, 0.25 mmol),phenylacetaldehyde (58 muL, 0.5 mmol) 2a, (DMEDA) (3 muL, 0.025mmol) were taken in a round bottom flask equipped with stirrer in 1.0mL of DMSO. The reaction mixture was heated to 80 C for 20 h.After cooling the room temperature, to the reaction mixture wasadded water (2 mL), and extracted with EtOAc (310 mL). Thecombined organic phases were washed with brine (25 mL), driedover anhydrous MgSO4 and concentrated in vacuo. The residue wassubjected to flash column chromatography with petroleum/ethylacetate (20/1) to afford the final product 4aa as light yellow solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With copper(l) iodide; sodium azide; potassium carbonate; N,N`-dimethylethylenediamine; In dimethyl sulfoxide; at 80℃; for 20h;Sealed tube; | General procedure: 2-iodoaniline (54.8 mg, 0.25 mmol) 1a, sodium azide (19.5 mg, 0.3mmol) 3, CuI (4.8 mg, 0.025 mmol), K2CO3 (34.5 mg, 0.25 mmol),phenylacetaldehyde (58 muL, 0.5 mmol) 2a, (DMEDA) (3 muL, 0.025mmol) were taken in a round bottom flask equipped with stirrer in 1.0mL of DMSO. The reaction mixture was heated to 80 C for 20 h.After cooling the room temperature, to the reaction mixture wasadded water (2 mL), and extracted with EtOAc (310 mL). Thecombined organic phases were washed with brine (25 mL), driedover anhydrous MgSO4 and concentrated in vacuo. The residue wassubjected to flash column chromatography with petroleum/ethylacetate (20/1) to afford the final product 4aa as light yellow solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | General procedure: To a two-necked round-bottomed flask fitted with a guard tube, PBr3 (2.7mmol, 0.26 mL), DMF (3 mmol, 0.23 mL) and chloroform (0.80 mL) were added, allowed to cool to 0 C and stirred for 0.5 h. After formation of colourless solid complex, 2-Iodo-4-methyl-phenylamine 2b (1 mmol) in chloroform (5 mL) was added and the reaction mixture was allowed to stir at r.t. for another 1-2 h. After completion, the reaction mixture was neutralized by adding saturated NaHCO3 solution and then extracted with DCM (3X 20 mL). Combined organic layer was washed with brine and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was purified through column chromatography using silica gel (60-120 mesh) and petether/EtOAc (5:1) as eluent. |
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