Structure of 913839-68-6
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CAS No. : | 913839-68-6 |
Formula : | C6H6N4 |
M.W : | 134.14 |
SMILES Code : | N#CC1=CC(NN)=NC=C1 |
MDL No. : | MFCD09813202 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H312-H315-H319-H332-H335-H351-H361 |
Precautionary Statements: | P201-P202-P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P308+P313-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501 |
* 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 |
---|---|---|
B. l-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)ethanone (24-bl) and 1- (2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)ethanone (24-b2) [00305] To a solution of l-(lH-indazol-6-yl)ethanone 24-a (200 mg, 1.25 mmol) in 4 mL DMF was added NaH (77 mg, 1.9 mmol) at 0-5 C, and the mixture was stirred for 1 h at 0-5 C. 2-(Trimethylsilyl)ethoxymethyl chloride (215 mg, 1.29 mmol) was then added. The mixture was stirred for 2 h prior to the addition of 5 mL H20. The reaction mixture was extracted (3 x 10 mL EtOAc), dried, and concentrated to dryness to give a mixture of the products 24-bl and 24-b2 (280 mg, 77%) as a yellow oil, which was used without further purification for the next synthetic step. [M+H] Calc'd for Ci5H22N202Si, 291; Found, 291. C . 3-(dimethylamino)- 1 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)prop- 2-en-l-one (24-cl) and 3-(dimethylamino)-l-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H- indazol-6-yl)prop-2-en- 1 -one (24-c2) [00307] To a regioisomeric mixture of compound 3 (700 mg, 2.4 mmol) in 10 mL DMF was added 2 mL DMF-DMA, and the mixture was heated to 115 C and stirred for 4 h. The reaction mixture was cooled and concentrated to dryness to give the crude product 24-cl and 24-c2 (900 mg, 100%) as a yellow oil, and was used without further purification for the next synthetic step. [M+H] Calc'd D. 2-(5-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)-lH-pyrazol-l- yl)isonicotinonitrile (24-dl) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- 1 -yl)isonicotinonitrile (24-d2) [00309] A mixture of compounds 24-cl and 24-c2 (900 mg, 2.6 mmol) and 2- hydrazinylpyridine-4-carbonitrile (350 mg, 2.6 mmol) in EtOH (10 mL) and AcOH (2 mL) was stirred at 90 C overnight. The reaction mixture was cooled, concentrated, and purified by prep-HPLC to afford compounds 24-dl and 24-d2 (390 mg, 36%), and was used without further purification for the next synthetic step. [M+H] Calc'd for C22H24N6OS1, 417; Found, 417. E . 2-(5 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)- 1 H-pyrazol- 1 - yl)isonicotinic acid (24-el) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- l-yl)isonicotinic acid (24-e2) [00311] To a solution of compounds 24-dl and 24-d2 (390 mg, 0.94 mmol) in EtOH (10 mL) was added 5 M NaOH (2 mL) at rt, then stirred at 90 C for 1 h. The reaction mixture was cooled, acidified with 1 N HC1 to pH = 3, filtered to give a yellow solid, and recrystallized from EtOH to afford compounds 24-el and 24-e2 (230 mg, 56%) as a white solid, which was used without further purification for the next synthetic step. [M+H] Calc'd for C22H25N5O3S1, 436; Found, 436. A. Methyl 2-(5-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)-lH-pyrazol- l-yl)isonicotinate (25-al) and methyl 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol- 6-yl)- 1 H-pyrazol- 1 -yl)isonicotinate (25 -a2) [00316] To a solution of compound 24-el and 24-e2 (50 mg, 0.12 mmol) in CH2C12/DMF (2 mL/1 drop) was added oxalyl chloride (0.5 mL), and the mixture was stirred for 1 h at rt. Then the reaction mixture was added dropwise to MeOH (1 mL), and the resultant mixture was stirred for 30 min at rt. Removal of volatiles provided compounds 25-al and 25 -a2 (60 mg, 100%) as a yellow solid, which was used without further purification for the next synthetic step. [M+H] Calc'd for C23H27N5O3S1, 450; Found, 450. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | B. l-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)ethanone (24-bl) and 1- (2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)ethanone (24-b2) [00305] To a solution of l-(lH-indazol-6-yl)ethanone 24-a (200 mg, 1.25 mmol) in 4 mL DMF was added NaH (77 mg, 1.9 mmol) at 0-5 C, and the mixture was stirred for 1 h at 0-5 C. 2-(Trimethylsilyl)ethoxymethyl chloride (215 mg, 1.29 mmol) was then added. The mixture was stirred for 2 h prior to the addition of 5 mL H20. The reaction mixture was extracted (3 x 10 mL EtOAc), dried, and concentrated to dryness to give a mixture of the products 24-bl and 24-b2 (280 mg, 77%) as a yellow oil, which was used without further purification for the next synthetic step. [M+H] Calc'd for Ci5H22N202Si, 291; Found, 291. C . 3-(dimethylamino)- 1 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)prop- 2-en-l-one (24-cl) and 3-(dimethylamino)-l-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H- indazol-6-yl)prop-2-en- 1 -one (24-c2) [00307] To a regioisomeric mixture of compound 3 (700 mg, 2.4 mmol) in 10 mL DMF was added 2 mL DMF-DMA, and the mixture was heated to 115 C and stirred for 4 h. The reaction mixture was cooled and concentrated to dryness to give the crude product 24-cl and 24-c2 (900 mg, 100%) as a yellow oil, and was used without further purification for the next synthetic step. [M+H] Calc'd D. 2-(5-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)-lH-pyrazol-l- yl)isonicotinonitrile (24-dl) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- 1 -yl)isonicotinonitrile (24-d2) [00309] A mixture of compounds 24-cl and 24-c2 (900 mg, 2.6 mmol) and 2- hydrazinylpyridine-4-carbonitrile (350 mg, 2.6 mmol) in EtOH (10 mL) and AcOH (2 mL) was stirred at 90 C overnight. The reaction mixture was cooled, concentrated, and purified by prep-HPLC to afford compounds 24-dl and 24-d2 (390 mg, 36%), and was used without further purification for the next synthetic step. [M+H] Calc'd for C22H24N6OS1, 417; Found, 417. E . 2-(5 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)- 1 H-pyrazol- 1 - yl)isonicotinic acid (24-el) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- l-yl)isonicotinic acid (24-e2) [00311] To a solution of compounds 24-dl and 24-d2 (390 mg, 0.94 mmol) in EtOH (10 mL) was added 5 M NaOH (2 mL) at rt, then stirred at 90 C for 1 h. The reaction mixture was cooled, acidified with 1 N HC1 to pH = 3, filtered to give a yellow solid, and recrystallized from EtOH to afford compounds 24-el and 24-e2 (230 mg, 56%) as a white solid, which was used without further purification for the next synthetic step. [M+H] Calc'd for C22H25N5O3S1, 436; Found, 436. A. Methyl 2-(5-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)-lH-pyrazol- l-yl)isonicotinate (25-al) and methyl 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol- 6-yl)- 1 H-pyrazol- 1 -yl)isonicotinate (25 -a2) [00316] To a solution of compound 24-el and 24-e2 (50 mg, 0.12 mmol) in CH2C12/DMF (2 mL/1 drop) was added oxalyl chloride (0.5 mL), and the mixture was stirred for 1 h at rt. Then the reaction mixture was added dropwise to MeOH (1 mL), and the resultant mixture was stirred for 30 min at rt. Removal of volatiles provided compounds 25-al and 25 -a2 (60 mg, 100%) as a yellow solid, which was used without further purification for the next synthetic step. [M+H] Calc'd for C23H27N5O3S1, 450; Found, 450. B. Methyl 2- [5 -(lH-indazol-6- l)-l H-pyrazol- l-yl]pyridine-4-carboxylate [00318] The solution of compounds 25-al and 25-a2 (60 mg, 0.12 mmol) in TFA/ CH2C12 (0.5 mL/2 mL) was stirred overnight at rt. The mixture was concentrated, and the residue was adjusted to pH = 8 with saturated aq. NaHC03. The mixture was extracted with CH2C12. The combined organic layers were washed with brine, dried over Na2S04, filtered, concentrated, and purified by prep-HPLC to afford the title compound (10 mg, 28%) as a yellow solid. 1H NMR (400 MHz, MeOD- d4): δ 3.96 (3H, s), 6.74(1H, d, J = 1.6 Hz), 7.00 (1H, dd, J = 8.4,1.2 Hz), 7.50 (1H, s), 7.74 (1H, d, J = 8.4 Hz), 7.87 (2H, m), 8.07(1 H, s), 8.13(1 H, s), 8.46 (1H, d, J = 7.2 Hz). [M+H] Calc'd for Ci7Hi3N502, 320; Found, 320. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | B. l-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)ethanone (24-bl) and 1- (2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)ethanone (24-b2) [00305] To a solution of l-(lH-indazol-6-yl)ethanone 24-a (200 mg, 1.25 mmol) in 4 mL DMF was added NaH (77 mg, 1.9 mmol) at 0-5 C, and the mixture was stirred for 1 h at 0-5 C. 2-(Trimethylsilyl)ethoxymethyl chloride (215 mg, 1.29 mmol) was then added. The mixture was stirred for 2 h prior to the addition of 5 mL H20. The reaction mixture was extracted (3 x 10 mL EtOAc), dried, and concentrated to dryness to give a mixture of the products 24-bl and 24-b2 (280 mg, 77%) as a yellow oil, which was used without further purification for the next synthetic step. [M+H] Calc'd for Ci5H22N202Si, 291; Found, 291. C . 3-(dimethylamino)- 1 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)prop- 2-en-l-one (24-cl) and 3-(dimethylamino)-l-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H- indazol-6-yl)prop-2-en- 1 -one (24-c2) [00307] To a regioisomeric mixture of compound 3 (700 mg, 2.4 mmol) in 10 mL DMF was added 2 mL DMF-DMA, and the mixture was heated to 115 C and stirred for 4 h. The reaction mixture was cooled and concentrated to dryness to give the crude product 24-cl and 24-c2 (900 mg, 100%) as a yellow oil, and was used without further purification for the next synthetic step. [M+H] Calc'd D. 2-(5-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)-lH-pyrazol-l- yl)isonicotinonitrile (24-dl) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- 1 -yl)isonicotinonitrile (24-d2) [00309] A mixture of compounds 24-cl and 24-c2 (900 mg, 2.6 mmol) and 2- hydrazinylpyridine-4-carbonitrile (350 mg, 2.6 mmol) in EtOH (10 mL) and AcOH (2 mL) was stirred at 90 C overnight. The reaction mixture was cooled, concentrated, and purified by prep-HPLC to afford compounds 24-dl and 24-d2 (390 mg, 36%), and was used without further purification for the next synthetic step. [M+H] Calc'd for C22H24N6OS1, 417; Found, 417. E . 2-(5 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)- 1 H-pyrazol- 1 - yl)isonicotinic acid (24-el) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- l-yl)isonicotinic acid (24-e2) [00311] To a solution of compounds 24-dl and 24-d2 (390 mg, 0.94 mmol) in EtOH (10 mL) was added 5 M NaOH (2 mL) at rt, then stirred at 90 C for 1 h. The reaction mixture was cooled, acidified with 1 N HC1 to pH = 3, filtered to give a yellow solid, and recrystallized from EtOH to afford compounds 24-el and 24-e2 (230 mg, 56%) as a white solid, which was used without further purification for the next synthetic step. [M+H] Calc'd for C22H25N5O3S1, 436; Found, 436. F. 2-[5-(lH-indazol-6-yl)-lH- razol-l-yl]pyridine-4-carboxylic acid [00313] The solution of compounds 24-el and 24-e2 (50 mg, 0.12 mmol) in HCl/EtOAc (6 M, 10 mmol) was stirred overnight at rt. The reaction mixture was filtered, and the solids were stirred with EtOAc /PE (0.5 mL/5 mL) for 1 h. After filtration, the solids were washed with hexane to give the title compound (13 mg, 37%) as a yellow solid. 1H NMR (400 MHz, MeOD-<): δ 6.75 (1H, s), 7.06 (1H, dd, J = 6.8, 1.6 Hz), 7.51 (1H, s), 7.77 (1H, d, J = 8.4 Hz), 7.88 (2H, s), 8.14 (2H, d, J = 1.2 Hz), 8.45 (1H, d, J = 2.0 Hz). [M+H] Calc'd for Ci6HiiN502, 306; Found, 306. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
B. l-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)ethanone (24-bl) and 1- (2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)ethanone (24-b2) [00305] To a solution of l-(lH-indazol-6-yl)ethanone 24-a (200 mg, 1.25 mmol) in 4 mL DMF was added NaH (77 mg, 1.9 mmol) at 0-5 C, and the mixture was stirred for 1 h at 0-5 C. 2-(Trimethylsilyl)ethoxymethyl chloride (215 mg, 1.29 mmol) was then added. The mixture was stirred for 2 h prior to the addition of 5 mL H20. The reaction mixture was extracted (3 x 10 mL EtOAc), dried, and concentrated to dryness to give a mixture of the products 24-bl and 24-b2 (280 mg, 77%) as a yellow oil, which was used without further purification for the next synthetic step. [M+H] Calc'd for Ci5H22N202Si, 291; Found, 291. C . 3-(dimethylamino)- 1 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)prop- 2-en-l-one (24-cl) and 3-(dimethylamino)-l-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H- indazol-6-yl)prop-2-en- 1 -one (24-c2) [00307] To a regioisomeric mixture of compound 3 (700 mg, 2.4 mmol) in 10 mL DMF was added 2 mL DMF-DMA, and the mixture was heated to 115 C and stirred for 4 h. The reaction mixture was cooled and concentrated to dryness to give the crude product 24-cl and 24-c2 (900 mg, 100%) as a yellow oil, and was used without further purification for the next synthetic step. [M+H] Calc'd D. 2-(5-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)-lH-pyrazol-l- yl)isonicotinonitrile (24-dl) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- 1 -yl)isonicotinonitrile (24-d2) [00309] A mixture of compounds 24-cl and 24-c2 (900 mg, 2.6 mmol) and 2- hydrazinylpyridine-4-carbonitrile (350 mg, 2.6 mmol) in EtOH (10 mL) and AcOH (2 mL) was stirred at 90 C overnight. The reaction mixture was cooled, concentrated, and purified by prep-HPLC to afford compounds 24-dl and 24-d2 (390 mg, 36%), and was used without further purification for the next synthetic step. [M+H] Calc'd for C22H24N6OS1, 417; Found, 417. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
B. l-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)ethanone (24-bl) and 1- (2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)ethanone (24-b2) [00305] To a solution of l-(lH-indazol-6-yl)ethanone 24-a (200 mg, 1.25 mmol) in 4 mL DMF was added NaH (77 mg, 1.9 mmol) at 0-5 C, and the mixture was stirred for 1 h at 0-5 C. 2-(Trimethylsilyl)ethoxymethyl chloride (215 mg, 1.29 mmol) was then added. The mixture was stirred for 2 h prior to the addition of 5 mL H20. The reaction mixture was extracted (3 x 10 mL EtOAc), dried, and concentrated to dryness to give a mixture of the products 24-bl and 24-b2 (280 mg, 77%) as a yellow oil, which was used without further purification for the next synthetic step. [M+H] Calc'd for Ci5H22N202Si, 291; Found, 291. C . 3-(dimethylamino)- 1 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)prop- 2-en-l-one (24-cl) and 3-(dimethylamino)-l-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H- indazol-6-yl)prop-2-en- 1 -one (24-c2) [00307] To a regioisomeric mixture of compound 3 (700 mg, 2.4 mmol) in 10 mL DMF was added 2 mL DMF-DMA, and the mixture was heated to 115 C and stirred for 4 h. The reaction mixture was cooled and concentrated to dryness to give the crude product 24-cl and 24-c2 (900 mg, 100%) as a yellow oil, and was used without further purification for the next synthetic step. [M+H] Calc'd D. 2-(5-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-indazol-6-yl)-lH-pyrazol-l- yl)isonicotinonitrile (24-dl) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- 1 -yl)isonicotinonitrile (24-d2) [00309] A mixture of compounds 24-cl and 24-c2 (900 mg, 2.6 mmol) and 2- hydrazinylpyridine-4-carbonitrile (350 mg, 2.6 mmol) in EtOH (10 mL) and AcOH (2 mL) was stirred at 90 C overnight. The reaction mixture was cooled, concentrated, and purified by prep-HPLC to afford compounds 24-dl and 24-d2 (390 mg, 36%), and was used without further purification for the next synthetic step. [M+H] Calc'd for C22H24N6OS1, 417; Found, 417. E . 2-(5 -( 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1 H-indazol-6-yl)- 1 H-pyrazol- 1 - yl)isonicotinic acid (24-el) and 2-(5-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-6-yl)- 1 H-pyrazol- l-yl)isonicotinic acid (24-e2) [00311] To a solution of compounds 24-dl and 24-d2 (390 mg, 0.94 mmol) in EtOH (10 mL) was added 5 M NaOH (2 mL) at rt, then stirred at 90 C for 1 h. The reaction mixture was cooled, acidified with 1 N HC1 to pH = 3, filtered to give a yellow solid, and recrystallized from EtOH to afford compounds 24-el and 24-e2 (230 mg, 56%) as a white solid, which was used without further purification for the next synthetic step. [M+H] Calc'd for C22H25N5O3S1, 436; Found, 436. |