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Chemical Structure| 189559-85-1 Chemical Structure| 189559-85-1

Structure of 189559-85-1

Chemical Structure| 189559-85-1

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Product Details of [ 189559-85-1 ]

CAS No. :189559-85-1
Formula : C9H8N2O
M.W : 160.17
SMILES Code : CC(C1=CC2=C(C=C1)C=NN2)=O
MDL No. :MFCD11869764
InChI Key :PCVRYEUFVDIBFI-UHFFFAOYSA-N
Pubchem ID :44119223

Safety of [ 189559-85-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 189559-85-1 ]

* 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.

  • Downstream synthetic route of [ 189559-85-1 ]

[ 189559-85-1 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 189559-85-1 ]
  • [ 1239480-86-4 ]
YieldReaction ConditionsOperation in experiment
With pyrrolidone hydrotribromide; In tetrahydrofuran; for 2h;Heating / reflux; Example 176Synthesis of {6-[5-(lH-Indazol-6-yl)-lH-imidazol-2-yl]-lH-benzimidazol-2-yl}-(2- trifluoromethylphenyl)-amineMethyl-3-nitroacetophenone (10 mmol) was reduced under hydrogenation conditions as described in general procedure F to afford l-(3-amino-4-methyl-phenyl)ethanone (1.4 g).Concentrated HCl (2 mL) was added to a mixture of l-(3-amino-4-methyl- phenyl)ethanone (8.4 mmol) and NaBF4 (1.2 g, 11 mmol) in H2O (10 mL) and the solution was cooled to 0 0C. A solution OfNaNO2 (0.58 g, 8.4 mmol) in H2O (1.5 mL) was added dropwise and the mixture was stirred at 00C for 30 min. The solid that formed was collected by filtration and washed with H2O (5 mL) followed by Et2O (5 mL) and dried under a reduced pressure. CH2Cl2 (20 mL), KOAc (0.91 g, 9.3 mmol) and 18-crown-6 (50 mg, 0.2 mmol) was added to the solid and the mixture was stirred at room temperature for 4 h. H2O <n="97"/>(20 mL) was added and the layers were separated. The organic layer was dried (MgSO4) and the solvent removed at reduced pressure to afford l-(lH-indazol-6-yl)ethanone (0.52 g). Pyrrolidone hydrotribromide (1.8 g, 3.6 mmol) was added to a solution of 1-(1H- indazol-6-yl)ethanone (0.5 g, 3 mmol) in THF (10 mL) and the solution was heated at reflux for 2 h. The solution was allowed to cool to room temperature and H2O (30 mL) was added and the mixture was extracted with EtOAc (3 x 20 mL) and dried (MgSO4). The solvent was removed at reduced pressure to afford 2-bromo-l-(lH-indazol-6-yl)-ethanone, which was used directly in the next step with no purification.DIEA (0.7 mL, 3.6 mmol) was added to a solution of 2-bromo-l-(lH-indazol-6- yl)ethanone (3 mmol) and 4-amino-3-nitrobenzoic acid (0.643 g, 3.5 mmol) in DMF (10 mL) and the solution was stirred at room temperature for 2 h. NH4OAc (5 g, 65 mmol) was added to the solution, followed by HOAc (10 mL) and the mixture was stirred at 140 0C for 2 h. The mixture was cooled to room temperature and poured into H2O (30 mL). The precipitate was collected by filtration, washed with H2O (10 mL) and dried under reduced pressure to afford 4-[5-(lH-indazol-6-yl)-lH-imidazol-2-yl]-2-nitrophenylamine (0.56 g).The nitro aniline from above (1 mmol) was reduced under hydrogenation conditions as described in general procedure F to afford 4-[5-(lH-indazol-6-yl)-lH-imidazol-2-yl]- benzene- 1 ,2-diamine.The diamine (0.5 mmol) from above was reacted with l-isothiocyanato-2- trifiuoromethylbenzene (0.5 mmol) followed by cyclization in situ using EDC as described in general procedure B to provide {6-[5-(lH-Indazol-6-yl)-lH-imidazol-2-yl]-lH-benzimidazol- 2-yl}-(2-trifluoromethylphenyl)-amine. MS: m/z 460 (M+H)+.
  • 2
  • BF4(1-)*C9H9N2O(1+) [ No CAS ]
  • [ 189559-85-1 ]
YieldReaction ConditionsOperation in experiment
With 18-crown-6 ether; potassium acetate; In dichloromethane; at 20℃; for 4h; Example 176; Synthesis of {6-[5-(lH-Indazol-6-yl)-lH-imidazol-2-yl]-lH-benzimidazol-2-yl}-(2- trifluoromethylphenyl)-amineMethyl-3-nitroacetophenone (10 mmol) was reduced under hydrogenation conditions as described in general procedure F to afford l-(3-amino-4-methyl-phenyl)ethanone (1.4 g).Concentrated HCl (2 mL) was added to a mixture of l-(3-amino-4-methyl- phenyl)ethanone (8.4 mmol) and NaBF4 (1.2 g, 11 mmol) in H2O (10 mL) and the solution was cooled to 0 0C. A solution OfNaNO2 (0.58 g, 8.4 mmol) in H2O (1.5 mL) was added dropwise and the mixture was stirred at 00C for 30 min. The solid that formed was collected by filtration and washed with H2O (5 mL) followed by Et2O (5 mL) and dried under a reduced pressure. CH2Cl2 (20 mL), KOAc (0.91 g, 9.3 mmol) and 18-crown-6 (50 mg, 0.2 mmol) was added to the solid and the mixture was stirred at room temperature for 4 h. H2O <n="97"/>(20 mL) was added and the layers were separated. The organic layer was dried (MgSO4) and the solvent removed at reduced pressure to afford l-(lH-indazol-6-yl)ethanone (0.52 g). Pyrrolidone hydrotribromide (1.8 g, 3.6 mmol) was added to a solution of 1-(1H- indazol-6-yl)ethanone (0.5 g, 3 mmol) in THF (10 mL) and the solution was heated at reflux for 2 h. The solution was allowed to cool to room temperature and H2O (30 mL) was added and the mixture was extracted with EtOAc (3 x 20 mL) and dried (MgSO4). The solvent was removed at reduced pressure to afford 2-bromo-l-(lH-indazol-6-yl)-ethanone, which was used directly in the next step with no purification.DIEA (0.7 mL, 3.6 mmol) was added to a solution of 2-bromo-l-(lH-indazol-6- yl)ethanone (3 mmol) and 4-amino-3-nitrobenzoic acid (0.643 g, 3.5 mmol) in DMF (10 mL) and the solution was stirred at room temperature for 2 h. NH4OAc (5 g, 65 mmol) was added to the solution, followed by HOAc (10 mL) and the mixture was stirred at 140 0C for 2 h. The mixture was cooled to room temperature and poured into H2O (30 mL). The precipitate was collected by filtration, washed with H2O (10 mL) and dried under reduced pressure to afford 4-[5-(lH-indazol-6-yl)-lH-imidazol-2-yl]-2-nitrophenylamine (0.56 g).The nitro aniline from above (1 mmol) was reduced under hydrogenation conditions as described in general procedure F to afford 4-[5-(lH-indazol-6-yl)-lH-imidazol-2-yl]- benzene- 1 ,2-diamine.The diamine (0.5 mmol) from above was reacted with l-isothiocyanato-2- trifiuoromethylbenzene (0.5 mmol) followed by cyclization in situ using EDC as described in general procedure B to provide {6-[5-(lH-Indazol-6-yl)-lH-imidazol-2-yl]-lH-benzimidazol- 2-yl}-(2-trifluoromethylphenyl)-amine. MS: m/z 460 (M+H)+.
  • 3
  • [ 59-48-3 ]
  • [ 189559-85-1 ]
  • [ 1168721-34-3 ]
YieldReaction ConditionsOperation in experiment
16% With pyrrolidine; In toluene; at 50℃;Reflux; A solution of oxindole (16 mg, 0.12 mmol), pyrrolidine (10 μL, 0.12 mmol) and l-(lH-indazol-6-yl)ethanone (20 mg, 0.12 mmol) in toluene was refluxed in a Dean-Stark trap for 2 h. The solution was then stirred at 50 0C for 72 h. Two equivalents of pyrrolidine were added and the solution was heated to reflux for 48 h. The solution was concentrated and the red residue was purified by preparatory HPLC to give the title compound as an orange solid (5 mg, 16%). 1H NMR (400 MHz, CDCl3) δ 8.13 (s, IH), 7.78 (s, IH), 7.70 (d, IH, J = 8.5 Hz), 7.34 (d, IH, J = 8.5 Hz), 7.03 (t, IH, J = 7.6 Hz), 6.81 (d, IH, J = 7.7 Hz), 6.50 (t, IH, J = 7.6 Hz), 6.05 (d, IH, J = 7.7 Hz), 2.82 (s, 3H); MS ESI [M + H]+, calcd for [Ci7Hi3N3O +H]+ 276.1; found m/z 276.0.
  • 4
  • [ 181820-44-0 ]
  • [ 189559-85-1 ]
YieldReaction ConditionsOperation in experiment
72% With dipyridinium dichromate; In acetone; at 20℃; To a solution of l-(lH-indazol-6-yl)ethanol (100 mg, 0.6 mmol) in acetone (50 mL) was added PDC (1.11 g, 3 mmol). The mixture was stirred overnight at rt. The mixture was filtered through silica gel and purified by silica gel chromatography (4:1 EtO Ac/Hex) to give the title compound as a brown solid (70 mg, 72%). 1H NMR (400 MHz, CDCl3) δ 8.45 (s, IH), 8.23 (s, IH), 8.09-8.08 (m, IH), 7.56-7.54 (m, IH), 2.72 (s, 3H).
  • 5
  • [ 67-56-1 ]
  • [ 913839-68-6 ]
  • [ 189559-85-1 ]
  • [ 76513-69-4 ]
  • [ 33513-42-7 ]
  • [ 1613411-98-5 ]
  • [ 1613411-99-6 ]
YieldReaction ConditionsOperation 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.
  • 6
  • [ 67-56-1 ]
  • [ 913839-68-6 ]
  • [ 189559-85-1 ]
  • [ 76513-69-4 ]
  • [ 33513-42-7 ]
  • [ 1613410-11-9 ]
YieldReaction ConditionsOperation 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.
  • 7
  • [ 913839-68-6 ]
  • [ 189559-85-1 ]
  • [ 33513-42-7 ]
  • [ 1613410-10-8 ]
YieldReaction ConditionsOperation 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.
  • 8
  • [ 913839-68-6 ]
  • [ 189559-85-1 ]
  • [ 76513-69-4 ]
  • [ 33513-42-7 ]
  • [ 1613411-94-1 ]
  • [ 1613411-95-2 ]
YieldReaction ConditionsOperation 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.
  • 9
  • [ 913839-68-6 ]
  • [ 189559-85-1 ]
  • [ 76513-69-4 ]
  • [ 33513-42-7 ]
  • [ 1613411-96-3 ]
  • [ 1613411-97-4 ]
YieldReaction ConditionsOperation 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.
  • 10
  • [ 189559-85-1 ]
  • [ 76513-69-4 ]
  • [ 33513-42-7 ]
  • [ 1613411-92-9 ]
  • [ 1613411-93-0 ]
YieldReaction ConditionsOperation 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
  • 11
  • [ 189559-85-1 ]
  • [ 76513-69-4 ]
  • [ 1613411-90-7 ]
  • [ 1613411-91-8 ]
YieldReaction ConditionsOperation 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.
  • 12
  • [ 79762-54-2 ]
  • [ 78191-00-1 ]
  • [ 189559-85-1 ]
YieldReaction ConditionsOperation in experiment
9% A. l-(lH-indazol-6-yl)ethanone (24-a) [00303] To a solution of 6-bromo-lH-indazole (5.0 g, 25.4 mmol) in 40 mL THF was added dropwise n-BuLi (2.5M, 30mL, 76.2 mmol) at -65 C, and the mixture was stirred for 2 h. Then, N-methoxy-N-methylacetamide (2.9 g, 27.9 mmol) was added. The reaction mixture was stirred for another 2 h at -65 C, then quenched with 40 mL H20. The mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with 100 mL brine, dried, and concentrated to dryness. The residue was purified by flash column chromatography (PE/EA=40/1) to give the title compound 24-a (370 mg, 9%) as a yellow solid. [M+H] Calc'd for C9H8N20, 161; Found, 161.
 

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[ 189559-85-1 ]

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