Structure of 196205-06-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 196205-06-8 |
Formula : | C9H10N2 |
M.W : | 146.19 |
SMILES Code : | NC1=C(C)C2=C(NC=C2)C=C1 |
MDL No. : | MFCD08704548 |
InChI Key : | LLUMZCODEQVYRF-UHFFFAOYSA-N |
Pubchem ID : | 15434496 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
36% | In ethanol; at 90℃; for 14.0h; | EXAMPLE 26 Preparation of 2-methyl-4-(4-methyl-1H-indol-5-ylamino)thieno[2,3-b]pyridine-5-carbonitrile 4-Chloro-2-methylthieno[2,3-b]pyridine-5-carbonitrile (Example 10, 80 mg, 0.38 mmol) was treated with <strong>[196205-06-8]5-amino-4-methylindole</strong> (111 mg, 0.76 mmol) in 3 mL of ethanol. After heating at 90 C. for 14 hours in a sealed vial, the reaction was cooled and treated with 2 mL of water. The resulting precipitate was filtered and washed with ethanol to give 43 mg of 2-methyl-4-(4-methyl-1H-indol-5-ylamino)thieno[2,3-b]pyridine-5-carbonitrile as a brown solid (36% yield), HRMS (ESI) 319.1015 (M+H); HPLC retention time=13.4 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | palladium-carbon; In methanol; | 4-Methyl-5-aminoindole A solution of <strong>[165250-69-1]4-methyl-5-nitroindole</strong> (0.72 g, 4.1 mmol) in 50 mL of methanol was stirred with 50 mg of 10% Pd/C under H2 for 12 h. Reaction mixture was filtered and concentrated in vacuo to provide an oil (0.61 g, >95%) which was characterized as the desired product by NMR analysis and subjected to a following reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A mixture of 4-chloro-2-{3-[(dimethylamino)methyl]phenyl}thieno[2,3-b]pyridine-5-carbonitrile 24 (120 mg, 0.44 mmol) and 4-methyl-5-aminoindole (78 mg, 0.53 mmol) in 3 mL of 2-ethoxyethanol was heated at 120 C. for 16 hours. An additional 50 mg of 4-methyl-5-aminoindole was added and the mixture was heated at 90 C. for 24 hours. Another additional 28 mg of 4-methyl-5-aminoindole was added and the mixture was heated at 90 C. for 24 hours. The mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The aqueous phase was extracted with dichloromethane and the combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a gradient of 2 to 20% methanol in dichloromethane. Further purification by preparative thin layer chromatography developing with 20% methanol in ethyl acetate gave 14 mg of 2-{3-[(dimethylamino)methyl]phenyl}-4-[(4-methyl-1H-indol-5-yl)amino]thieno[2,3-b]pyridine-5-carbonitrile 187 as a tan solid, mp 227-229 C., MS 438.3 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; for 4.0h;Heating / reflux; | Methyl 4-chloro-5-cyanothieno[2,3-b]pyridine-2-carboxylate (1.3 g, 5.1 mmol) and 4-methyl-5-aminoindole (0.98 g, 6.7 mmol) were heated to reflux in 50 mL MeOH for 1 hour. An additional 0.35 g of 4-methyl-5-amino indole was added and the heating was continued for 3 hours. The reaction was cooled to room temperature and the resultant precipitate was filtered and washed with MeOH to give 1.3 g of methyl 5-cyano-4-[(4-methyl-1H-indol-5-yl)amino]thieno[2,3-b]pyridine-2-carboxylate 245, mp 255 C., MS (ESI) m/z 363.2 (M+H), HPLC retention time=14.2 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 80℃; for 20.0h;Product distribution / selectivity; | 4-Fluoro-2-iodothieno[2,3-b]pyridine-5-carbonitrile (75 mg, 0.25 mmol) and 4-methyl-5-aminoindole (72 mg, 0.5 mmol) were heated to 80 C. in 1.5 mL DMF for 20 hours. Upon cooling, the crude reaction mixture was purified by HPLC to give 2-iodo-4-(4-methyl-1H-indol-5-ylamino)thieno[2,3-b]pyridine-5-carbonitrile 123 MS (ESI) m/z 451.8 (M+H), HPLC retention time=9.50 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | EXAMPLE 44:PREPARATION OF 5-BROMO-6-METHYL-4-[(4-METHYL-1 H-INDOL-5- YL)AMINO]NICOTINONITRILEA mixture of 5-bromo-4-chloro-6-methylnicotinonitrile (2.00 g, 8.63 mmol) and 5- amino-4-methylindole (1.82 mg, 12.47 mmol) in 20 mL of ethanol was heated at reflux overnight. The resulting mixture was cooled slightly and filtered washing with ethanol. The solid was stirred with saturated aqueous sodium bicarbonate then the aqueous mixture was extracted with ethyl acetate. The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated with diethyl ether to give 1.21 g (41%) of 5-bromo-6-methyl-4-[(4-methyl- 1 H-indol-5-yl)amino]nicotinonitrile as an off-white solid, MS 341.2 (M+H); HPLC 99.2% at 215 nm, 9.5 min; Prodigy ODS3, 0.46 x 15 cm column, 1.0 mL/min, 20min gradient of acetonitrile in water/trifluoroacetic acid. | |
41% | Mixture of 5-bromo-4-chloro-6-methylnicotinonitrile (2.00 g, 8.63 mmol) and 5-amino-4- methylindole (1.82 mg, 12.47 mmol) in 20 mL of ethanol was heated at reflux overnight. The resulting mixture was cooled slightly and filtered washing with ethanol. The solid was stirred with saturated aqueous sodium bicarbonate then the aqueous mixture was extracted with ethyl acetate. The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated with diethyl ether to give 1.21 g (41%) of 5-bromo-6-methyl-4-[(4-methyl- 1H-indol-5-yl)amino]nicotinonitrile as an off-white solid; MS 341.2 (M+H); HPLC: 99.2% at 215 nm, 9.5 min [a]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; for 44.0h;Heating / reflux; | EXAMPLE 60:PREPARATION OF 6-ETHYL-5-IODO-4-(4-METHYL-1 H-INDOL-5- YLAMINO)NICOTINONITRILEA reaction mixture of 4-chloro-6-ethyl-5-iodonicotinonitrile (160 mg, 0.55 mmol) and <strong>[196205-06-8]5-amino-4-methylindole</strong> (80 mg, 0.55 mmol) in anhydrous ethanol (2.0 mL) was heated at reflux for 44 h. After cooling to room temperature, the reaction mixture was added to 10 mL of H2O, then extracted three times with a 1 :3 mixture of tetrahydrofuran: ethyl acetate. The combined organic layers were washed with H2O, dried over Na2SO4, filtered and concentrated to provide 230 mg of crude 6-ethyl-5- iodo-4-(4-methyl-1 H-indol-5-ylamino)nicotinonitrile as a dark solid which was used directly in the next reaction without further purification. MS 403.1 (M + H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In ethanol; for 48.0h;Heating / reflux; | EXAMPLE 62:PREPARATION OF 5-BROMO-6-ETHYL-4-(4-METHYL-1 H-INDOL-5-YLAMINO)- NICOTINONITRILEA reaction mixture of 5-bromo-4-chloro-6-ethylnicotinonitrile (71 mg, 0.29 mmol) and <strong>[196205-06-8]5-amino-4-methylindole</strong> (42 mg, 0.29 mmol) in anhydrous ethanol (1.0 mL) was heated at reflux for 48 h. After cooling to room temperature, the reaction mixture was added to 10 mL of H2O and filtered. The solid residue was washed with H2O and diethyl ether then dried in vacuo to provide a quantitative amount of crude 5-bromo- 6-ethyl-4-(4-methyl-1 H-indol-5-ylamino)-nicotinonitrile as a dark solid that was used directly without further purification. MS 355 (M + H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In ethanol; for 72.0h;Heating / reflux; | A mixture of 4-chloro-5-iodonicotinonitrile (5.0 g, 18.9 mmol) and <strong>[196205-06-8]5-amino-4-methylindole</strong> (3.0 g, 20.8 mmol) in EtOH (100 mL) was heated at reflux for 3 days, cooled to r.t and diluted with saturated aq. Na2SO4 (300 mL). The precipitated solids were collected by filtration, washed with water and dried to give 5.3 g (75%) of 5-iodo-4-[(4-methyl-1H-indol-5- yl)amino]nicotinonitrile as a grey solid, mp 192-1940C; MS (M+l-T): 375.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; for 48.0h;Heating / reflux; | 5-Bromo-4-chloro-6-ethylnicotinonitrile (71 mg, 0.29 mmol) contaminated with a small amount of the corresponding isopropyl derivative was combined with 5-amino-4-methyl indole (42 mg, 0.29 mmol) in anhydrous ethanol (1.0 mL) and heated at reflux for 48 h. After cooling to room temperature, the reaction mixture was added to 10 mL of H2O and filtered. The solid residue was washed with H2O and diethyl ether then dried in vacuo to provide a quantitative amount of crude 5-brom-6-ethyl-4-(4-methyl-1H-indol-5-ylamino)nicotinonitrile as a dark solid which was used directly without further purification; MS 355 (M+H). The product was contaminated with small amounts of the corresponding isopropyl derivative. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; for 96.0h;Heating / reflux; | delta-iodo-beta-methyM-oxo-M-dihydropyridine-S-carboxamide (4.0 g, 14.4 mmol) and 5-amino-4- methylindole (2.7 g, 18.7 mmol) were heated to a vigorous reflux in 100 ml_ EtOH. After heating for 4 days, the reaction was cooled and the grey solid was filtered to give 3.4 g of 5- iodo-6-methyl-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile, mp 222-223C; MS 389.2 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | A mixture of 5-bromo-4-chloronicotinonitrile (1.40 g, 6.43 mmol), <strong>[196205-06-8]5-amino-4-methylindole</strong> (0.94 g, 6.43 mmol) in 15 ml. of ethanol was heated at reflux overnight, then cooled to room temperature. The precipitate was filtered and washed with ethanol twice and diethyl ether once, then air-dried. The resultant HCI salt was suspended in methanol, treated with cone, aqueous ammonium hydroxide and concentrated in vacuo to dryness. The solid residue was washed with water and diethyl ether to give 1.3 g (62%) of 5-bromo-4-[(4-methyl-1 H-indol-5- yl)amino]nicotinonitrile as a pale gray solid; MS 327.1, 329.1 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The mixture of 3-(bromomethyl)-4-chlorothieno[2,3-b]pyridine-5-carbonitrile and 4-bromo-3-(bromomethyl)thieno[2,3-b]pyridine-5-carbonitrile (150 mg, 0.52 mmol) was treated with CaCO3 (261 mg, 2.6 mmol) and heated to 80 C. overnight in 4 mL of 1:1 dioxane:water. The reaction was partitioned between EtOAc and dilute aqueous HCl. The organic layer was concentrated to give a yellow solid which was treated with 4-methyl-5-aminoindole (114 mg, 0.78 mmol) and 5 mL EtOH. The reaction was heated to 80 C. overnight. 3-(Hydroxymethyl)-4-[(4-methyl-1H-indol-5-yl)amino]thieno[2,3-b]pyridine-5-carbonitrile 496 was isolated after purification by preparative HPLC, mp 230 C.; MS (ESI) m/z 335.2 (M+H); HPLC retention time=11.1 min. |
A329244 [5054-94-4]
(2,3-Dimethyl-1H-indol-5-yl)methanamine
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