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CAS No. : | 202197-31-7 | MDL No. : | MFCD08061259 |
Formula : | C14H12FN3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 241.26 | Pubchem ID : | - |
Synonyms : |
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Signal Word: | Class: | ||
Precautionary Statements: | UN#: | ||
Hazard Statements: | Packing Group: |
* 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 |
---|---|---|
33% | With Ki; potassium carbonate In water; N,N-dimethyl-formamide | E. Preparation of 1-(3-Fluoro-benzyl)-1H-indazol-5-ylamine A mixture of 5-nitro-1H-indazole (8.15 gm, 50 mmole), m-fluoro-benzyl chloride (7.95 gm, 1.1 equiv), K2CO3 (7.59 gm, 1.1 equiv), and KI (8.47 gm, 1.02 equiv) in dry DMF (75 mL) was heated at 70° C. overnight. After cooling to RT, water (75 mL) was slowly added to give a precipitate that consisted of about a one to one mixture of isomers [HPLC Ret Time: 1.92 (1-substitued isomer vs. 2.03 (2-substituted isomer) YMC C18 S5 4.6*50 mm, 3 min gradient, 4 mL/min]. This was collected by filtration and washed with water. The solid was crystallized twice from acetone/water to afford the desired 1-(3-fluoro-benzyl)-5-nitro-1H-indazole (4.47 gm, 33percent). A suspension of this material (3.00 gm, 11.1) and 10percent Pd/C (3.00 gm) in EtOH (21 mL) was kept under an H2 atmosphere (balloon) for 24 hr. The catalyst was removed by filtration and the solvent was evaporated to leave the product as a solid (2.4 gm, 90percent). 1H NMR (CDCl3): δ 3.61 (br s, 2H), 5.52 (s, 2H), 6.81-7.85 (m, 7H), 7.85 (s, 1H); MS: 242 (M+H)+; HPLC Ret Time: 1.03 min (YMC Xterra ODS S7, 3.0*50 mm column, 2 min gradient, 5 mL/min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With hydrogen;5%-palladium/activated carbon; In methanol; for 2h; | A solution of Compound 4c (2.0 g, 7.37 mmol) in MeOH (60 mL) was added to 5% Pd/C (0.2 g) under nitrogen. The reaction mixture was stirred for 2 hours under hydrogen atmosphere and then filtered through celite. The filtrate was evaporated in vacuo to yield l-(3- fluoro-benzyl)-lH-indazol-5-ylamine Compound 4d (1.72 g, 97%) as a solid. 1H NMR (400 MHz, CDCl3) delta 7.84 (IH, d), 7.28-7.21 (IH, m), 7.13 (IH, d, J= 8.8 Hz), 9.96-6.90 (3H, m), 6.84-6.81 (2H, m), 5.52 (2H, s), 3.60 (2H, br s); MS (ES+) m/z 242.1 (MH+). |
95.42% | With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃; for 10h; | The compound <strong>[529508-58-5]1-(3-fluorobenzyl)-5-nitro-1H-indazole</strong> (17.2 g, 63.5 mmol) was added to methanol (600 mL).Then 10% palladium on carbon (1.72 g) was added to the above solution.After replacing H2 three times,The reaction was stirred at 25 C for 10.0 h. Filtering,The filter cake was washed with methanol (150 mL), the filtrate was combined and concentrated.14.6 g of a reddish brown solid were obtained in a yield: 95.42%.This solid was used in the next reaction without purification. |
90.8% | With hydrogen;platinum on carbon; In ethanol; water; at 60℃; for 4h; | Follow modified procedure from WO 99/35146. 1- (3-FLUORO-BENZYL)-5-NITRO-LH-INDAZOLE (2.49 g, 9.2 mmol) is suspended in 40 ml absolute ETOH and Pt/C (5%, wet, 150 mg) is added. The reaction mixture is stirred and heated at 60 C under a hydrogen atmosphere (balloon). Roughly 4 hours into the reaction LC/MS reveals the formation of substantial amounts of product. The mixture is filtered through Celite and concentrated under reduced pressure. Yield: 2. 01 g (90. 8%) of a white solid. |
90.8% | With hydrogen;platinum on carbon; In ethanol; at 60℃; for 4h; | Step B: 1-(3-Fluoro-benzyl)-1 H-indazol-5-ylamine Follow modified procedure from WO 99/35146. <strong>[529508-58-5]1-(3-Fluoro-benzyl)-5-nitro-1H-indazole</strong> (2.49 g, 9.2 mmol) is suspended in 40 ml absolute EtOH and Pt/C (5%, wet, 150 mg) is added. The reaction mixture is stirred and heated at 60 C. under a hydrogen atmosphere (balloon). Roughly 4 hours into the reaction LC/MS reveals the formation of substantial amounts of product. The mixture is filtered through Celite and concentrated under reduced pressure. Yield: 2.01 g (90.8%) of a white solid. |
84% | With hydrogen; In tetrahydrofuran; at 30 - 40℃; under 775.743 Torr; for 1h; | Benzyl nitro indazole (1 equiv.) was charged to a hyrdogenator, THF (8 volumes) was added and hydrogenated atl5 psi between 30-40 C. The reaction mixture was held for-1 h (s. m. <3% by HPLC) cooled to 25 C, the catalyst was filtered and the mixture was washed with THF (0.9 volumes). The mixture was transferred to another vessel, rinsed again with THF (0.4 volumes) distilled to the desired volume (5.5 volumes) atmospherically, and heptane was added (15 volumes) between 47-60 C over lh. The slurry was cooled over 1. 5h to 18-23 C. The slurry was held for 1h, filtered and washed with THF/heptane (1: 4,10. 4 volumes) and dried in oven <45 C, (LOD <1%). yield was 84%. melting point = 130C. HPLC Ret Time: 9.09 min |
76% | With iron; acetic acid; In ethyl acetate; at 20℃; for 36h; | 5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL, 119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 C for 12h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5:1 to 4:1 Hex/EtOAc), yielding 5-nitro-l-N-(3-fluorobenzyl) indazole (7.9 g, 32%) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37%) as yellow solids. 5-nitro-l-N-(3-fluorobenzyl) indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g , 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3 x 500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4:1 to 3:1) to give 5-amino-l-N-(3- fluorobenzyl) indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-O6) delta 7.72 (s, IH), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT = 1.66 min; [M+H]+ = 242.2. |
76% | With iron; acetic acid; In ethyl acetate; at 20℃; for 36h; | 5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL,119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70 C for 12h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5: 1 to 4: 1 Hex/EtOAc), yielding 5-nitro-1-N-(3-fluorobenzyl) indazole (7.9 g, 32%) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37%) as yellow solids.5-nitro-1-N-(3-fluorobenzyl) indazole (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g , 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3 x 500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4: 1 to 3: 1) to give 5-amino-1-N-(3-fluorobenzyl) indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-d6) delta 7.72 (s, 1H), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT = 1.66 min; [M+H]+ = 242.2. |
76% | <strong>[529508-58-5]5-nitro-1-N-(3-fluorobenzyl)indazole</strong> (7.9 g, 29.1 mmol, 1 equiv) and iron (8.13 g, 145.6 mmol, 5 equiv) were mixed in 200 mL acetic acid and 50 mL EtOAc, and were stirred at rt for 36 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to 10 mL volume. The contents were diluted with water (10 mL) and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc (3×500 mL), the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was purified by column chromatography eluting with hexanes/EtOAC (4:1 to 3:1) to give 5-amino-1-N-(3-fluorobenzyl)indazole (5.32 g, 76%) as a light brown solid. 1H-NMR (DMSO-d6) delta 7.72 (s, 1H), 7.22-7.36 (m, 2H), 6.87-7.05 (m, 3H), 6.70-6.77 (m, 2H), 5.48 (s, 2H), 4.78 (br s, 2H); LCMS RT=1.66 min; [M+H]+=242.2. | |
With hydrogen;palladium 10% on activated carbon; In methanol; for 14h; | Step B: l-(3-fluorobenzyl)-lH-indazol-5-amine (compound 16.2).[0158] A suspension of compound 16.1 (2.71 g, 10 mmol) and palladium 10% on carbon (1.Og, wet) in methanol (40 mL) was hydrogenated under a hydrogen balloon for 14 hours. The reaction mixture was then filtered through Celite (20 g), rinsed withdichloromethane/methanol (3/1), and concentrated to give the title compound as a white crystalline solid (2.40 g, 100%). The product is used without further purification. LCMS ESI(+) m/z: 242 (M+ 1). | |
With hydrogen;Raney's nickel; In methanol; at 20℃;Inert atmosphere; | Under N2, Raney's nickel (0.53g, wet weight) was added to a solution of 1-b (5.3 g, 19.7mmol) in methanol (20 mL) and the mixture was degassed and stirred under hydrogen atmosphere at room temperature overnight. The catalyst was carefully filtered and the filtrate was concentrated in vacuum to give 1-c (4.65 g, 5.28 mmol). | |
With hydrogen; In methanol; at 20℃;Inert atmosphere; | [050] Under N2; Raney's nickel (0.53 g, wet weight) was added to a solution of 1-b (5.3 g, 19.7 mmol) in methanol (20 mL) and the mixture was degassed and stirred under hydrogen atmosphere at room temperature overnight. The catalyst was carefully filtered and the filtrate was concentrated in vacuum to give 1-c (4.65 g, 19.3 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | In 1,2-dichloro-ethane; tert-butyl alcohol; at 90℃; for 8h; | Step C: [1-(3-Fluoro-benzyl)-1 H-indazol-5-yl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride Follow general procedure from Example 1, step E. <strong>[98556-31-1]4-chloro-6-iodoquinazoline</strong> (1.18 g, 4.06 mmol) is mixed with 1-(3-Fluoro-benzyl)-1H-indazol-5-ylamine (1.09 g, 4.52 mmol), and a mixture of DCE (10 ml) and t-BuOH (10 ml) is added. The mixture is heated at 90 C. (oil bath temperature) for 8 hours. At 5 hours of heating LC/MS reveals substantial amount of product. Yield is 1.35 g (56%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With N-ethyl-N,N-diisopropylamine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran | 1.F F. F. Preparation of (5-Benzenesulrinylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-amine A solution of 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine (850 mg, 3.46 mmole) in DCM (30 mL) was sparged with N2 for 0.5 hr and then placed in a -20° C. bath. Thiophenol (384 μL, 1.0 equiv) and diisopropylethylamine (605 μL, 1.0 equiv) were added and the reaction was kept at -20° C. for 3 hr. After warming to RT, the reaction mixture was washed with water, dried (Na2SO4), and the solvent was removed. 1,2-Dichloroethane (10 mL), n-butanol (10 mL) and 1-(3-fluoro-benzyl)-1H-indazol-5-ylamine (750 mg, 0.9 equiv) were added to the residue and this mixture was heated at 85° C. for 2.5 hr. The solvents were removed and the residue was taken up in DCM, washed with sat. aq NaHCO3 solution and dried (Na2SO4). Removal of the solvent followed by chromatography on silica gel using DCM containing 0 to 2% MeOH as eluent afforded [1-(3-fluoro-benzyl)-1H-indazol-5-yl]-(5-phenylsulfanylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-amine (957 mg, 58%) as a foam. 1H NMR (CDCl3) δ 4.48 (s, 2H), 5.59 (s, 2H), 6.53 (d, 1H, J=3 Hz), 6.8-7.0 (m, 3H), 7.2-7.6 (m, 9H), 7.95 (s, 1H), 8.06 (s, 1H), 8.15 (d, 1H, J=2 Hz), 8.88 (br s, 1H); MS: 481 (M+H)+; HPLC Ret Time: 1.87 min (YMC S7 C18, 3.0*50 mm column, 2 min gradient, 5 mL/min). This was dissolved in chloroform (25 mL), cooled in an ice bath and m-chloro-perbenzoic acid (500 mg, 57 to 80%, 1 equiv) was added in small portions over 15 min. After 1 hr., the reaction was washed with 10% aqueous NaHSO3 solution, sat. aq. NaHCO3 solution (three times) and dried (Na2SO4). Removal of the solvent left the product as a foam (957 mg, 95%). 1H NMR (CDCl3) δ 4.28 (d, 1H, J=14 Hz), 4.53 (d, 1H, J=14 Hz), 5.60 (s, 2H), 6.13 (d, 1H, J=3 Hz), 6.8-7.6 (m, 11H), 7.71 (dd, 1H, J=2, 9 Hz), 7.98 (s, 1H), 8.05 (s, 1H), 8.14 (d, 1H, J=2 Hz); MS: 497 (M+H)+; HPLC Ret Time: 1.67 min (YMC S7 C18, 3.0*50 mm column, 2 min gradient, 5 mL/min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33%; 90% | With Ki; potassium carbonate; In water; N,N-dimethyl-formamide; | E. Preparation of 1-(3-Fluoro-benzyl)-1H-indazol-5-ylamine A mixture of 5-nitro-1H-indazole (8.15 gm, 50 mmole), m-fluoro-benzyl chloride (7.95 gm, 1.1 equiv), K2CO3 (7.59 gm, 1.1 equiv), and KI (8.47 gm, 1.02 equiv) in dry DMF (75 mL) was heated at 70 C. overnight. After cooling to RT, water (75 mL) was slowly added to give a precipitate that consisted of about a one to one mixture of isomers [HPLC Ret Time: 1.92 (1-substitued isomer vs. 2.03 (2-substituted isomer) YMC C18 S5 4.6*50 mm, 3 min gradient, 4 mL/min]. This was collected by filtration and washed with water. The solid was crystallized twice from acetone/water to afford the desired 1-(3-fluoro-benzyl)-5-nitro-1H-indazole (4.47 gm, 33%). A suspension of this material (3.00 gm, 11.1) and 10% Pd/C (3.00 gm) in EtOH (21 mL) was kept under an H2 atmosphere (balloon) for 24 hr. The catalyst was removed by filtration and the solvent was evaporated to leave the product as a solid (2.4 gm, 90%). 1H NMR (CDCl3): delta 3.61 (br s, 2H), 5.52 (s, 2H), 6.81-7.85 (m, 7H), 7.85 (s, 1H); MS: 242 (M+H)+; HPLC Ret Time: 1.03 min (YMC Xterra ODS S7, 3.0*50 mm column, 2 min gradient, 5 mL/min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With sodium hydrogencarbonate In methanol; acetonitrile | 93 [1-(3-Fluoro-benzyl)-1H-indazol-5yl]-[5-(piperidin-4-yloxymethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-amine EXAMPLE 93 [1-(3-Fluoro-benzyl)-1H-indazol-5yl]-[5-(piperidin-4-yloxymethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-amine A suspension of 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine (61 mg, 0.25 mmole), 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 10 equiv) and NaHCO3 (42 mg, 2 equiv) in dry CH3CN (0.5 mL) under N2 was left stirring at RT for 3 days. 1-(3-Fluoro-benzyl)-1H-indazol-5-ylamine (54 mg, 0.9 equiv) and additional NaHCO3 (42 mg, 2 equiv) were added and the reaction was left stirring overnight. The reaction was diluted with DCM, washed with water, and dried (Na2SO4). Removal of the solvent followed by radial chromatography (2 mm silica gel plate, gradient elution with DCM containing 0 to 3% MeOH) afforded 4-{4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethoxy}-piperidine-1-carboxylic acid tert-butyl ester as a foam (47 mg, 33%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium hydrogencarbonate; sodium sulfate In hexane; water; acetonitrile | 117.A A. A. Preparation of {4-[1-(3-Fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-methanol A mixture of crude 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine (3.69 gm, 0.015 moles and NaHCO3 (2.51 gm, 2 equiv) in a mixture of acetonitrile (50 mL) and water (5 mL) was stirred under a N2 atmosphere for 3 days. This was treated with Na2SO4 and then with 1-(3-flurobenzyl)-1H-indazol-5-ylamine (3.24 gm, 0.90 equiv) and NaHCO3 (1 gm) and left stirring for 18 hr at RT. The reaction was filtered and the filter cake was washed with DCM (100 mL). The filtrate was concentrated and silica gel chromatography (elution with 30% EtOAc in hexane) of the residue gave the title compound as a tan solid (3.78 gm, 65% yield): 1H NMR (CDCl3) δ 3.03 (t, J=5.9 Hz, 1H), 4.98 (d, J=5.7 Hz, 2H), 5.55 (s, 2H), 6.76 (d, J=2.7 Hz, 1H), 6.83 (d, J=9.0 Hz, 1H), 6.98-6.90 (m, 3H), 7.43 (d, J=2.5 Hz, 1H), 7.51 (dd, J=2.1, 8.8 Hz, 1H), 7.96 (s, 11H), 8.03 (s, 1H), 8.22 (s, 1H), 9.91 (s, 1H); MS: (M+H+); HPLC Ret Time: 2.38 min (YMC C18 S5, 3.0*50 mm, 4 min gradient, 4 mL/min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 2h; | A solution of Compound 4d (1.38 g, 5.74 mmol) in THF (8 mL) was added dropwise to a solution containing <strong>[5305-45-3]4,6-dichloro-pyrimidine-5-carbonitrile</strong> Compound Id (1.0 g, 5.74 mmol), EPO <DP n="98"/>THF (10 mL) and DIPEA (1.6 mL, 9.20 mmol) at RT. After 2 hours, the reaction mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed consecutively with aqueous 10% NH4Cl, water and brine. The organic layer was dried over Na2SO4, then filtered and concentrated down to a solid. Trituration with hexane gave 4-chloro-6-[l-(3- fluoro-benzy^-lH-indazol-S-ylaminoj-pyrimidine-S-carbonitrile Compound 4e (2.15 g, 99%) as a solid. 1H NMR (400 MHz, DMSO) delta 10.31 (IH, br s), 8.48 (IH, s), 8.15 (IH, d), 7.82 (IH, d), 7.82 (IH, d, J= 8.9 Hz), 7.44 (IH, dd, / = 1.9 Hz & 8.9 Hz), 7.37-7.35 (IH, m), 7.10- 7.03 (3H, m), 5.70 (2H, s); MS (ES+) m/z 379.0 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 100℃; for 2h; | A. Preparation of 4-amino-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbaldehyde To a mixture of <strong>[14160-93-1]4-amino-6-chloro-pyrimidine-5-carbaldehyde</strong> (95.5 mg, 0.61 mmol) and 1-(3-fluoro-benzyl)-1H-indazol-5-ylamine (147 mg, 0.61 mmol) in DMSO (1.5 mL) was added diisopropylethylamine (DIEA, 79 mg, 0.61 mmol). The mixture was stirred at 100 C. for 2 h, cooled to room temperature, then partitioned between ethyl acetate and H2O. The combined ethyl acetate extracts were dried over Na2SO4 and evaporated to afford a yellow solid, which was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane; for 3h;Reflux; | A mixture of <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (1-h, 1.2g, 5.02mmol) and l-(3-fluorobenzyl)-lH-indazol-5-amine (1-c, 1.2g, 4.98mmol) in dioxane (40mL) was heated to reflux for 3 h. It was then cooled to the ambient temperature. The precipitates were obtained by filtration and purified by chromatography on silica gel to give 1-i (1.7 g, 3.88 mmol) as yellow solid. | |
In 1,4-dioxane; for 3h;Reflux; | [055] A mixture of <strong>[55496-69-0]4-chloro-7-methoxy-6-nitroquinazoline</strong> (1-h, 1.2 g, 5.02 mmol) and l-(3-fluorobenzyl)-lH-indazol-5-amine (1-c, 1.2 g, 4.98 mmol) in dioxane (40 mL) was heated to reflux for 3 h. It was then cooled to the ambient temperature. The precipitates were obtained by filtration and purified by chromatography on silica gel to give 1-i (1.7 g, 3.88 mmol) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58.7% | With N-ethyl-N,N-diisopropylamine; In toluene; at 120℃; for 24.0h; | 4-Chloro-6-methylpyrimidine-5-carboxylic acid ethyl ester (5.9 g, 29.4 mmol), compound 1-(3-fluorobenzyl)-1H-indazole-5-amine (7.1 g, 29.4 mmol) and diisopropylethylamine (15.5 mL, 88 mmol) were dissolved in toluene (90 mL).The reaction was stirred to a temperature of 120 C for 24.0 h, the reaction mixture was concentrated, and the residue was recrystallized from isopropyl alcohol (50mL).Get 7.0g yellow solidBody, the yield was 58.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.7% | In isopropyl alcohol; at 85℃; for 2.5h; | Compound 4-Chloro-7-methoxyquinazolin-6-yl acetate (0.5 g, 1.99 mmol) and compound 1-(3-fluorobenzyl)-1H-indazole-5-amine (0.51 g , 1.99 mmol) dissolved in isopropanol (30 mL),Heat to 85 C and stir the reaction for 2.5 h.Cool to 25 C, filter, filter cake washed with isopropyl alcohol (5 mL),Drying gave 0.69 g of a yellow solid, yield 76.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃; for 12h;Inert atmosphere; | Under N2 protection,4-Chloro-6-iodoquinazoline (7.69 g, 26.5 mmol) was added to isopropanol (300 mL) and 1-(3-fluorobenzyl)-1H-indazole-5-amine (6.38) was added. g, 26.5mmol),N,N-diisopropylethylamine (8.6 g, 66.2 mmol)Slowly added to the above solution,The temperature was slowly raised to 80 C and the reaction was stirred for 12.0 h. The reaction solution was cooled to 25 C and filtered under reduced pressure.A pale yellow solid was obtained which was crystallised from isopropyl alcohol (60 mL) to yield 12.4 g of a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.2% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 25 - 80℃; for 8h; | At 25 C,The compound <strong>[63558-65-6]4-chloro-5-iodopyrimidine</strong> (4.1 g, 17.1 mmol) and the compound 1-(3-fluorobenzyl)-1H-benzo[d]imidazole-5-amine (4.3 g, 17.1 mmol)And diisopropylethylamine (5.96 g, 34.2 mmol)Soluble in ethanol (100mL),The temperature was raised to 80 C for 8.0 h, and the reaction solution was concentrated.Obtained a reddish brown oil,The oil was recrystallized from isopropanol (60 mL).Filtered and dried to give 6.2 g of a brown solid.The yield was 87.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 25 - 90℃; for 8h; | At 25 C,The compound <strong>[41103-17-7]4-chloropyrimidine-5-carboxylic acid ethyl ester</strong> (6.8 g, 0.04 mol) and the compound 5-amino-1-(3-fluorobenzyl)carbazole (7.7 g, 32 mmol)Soluble in dry acetonitrile (150 mL),Slowly add DIPEA (9.75g, 0.075mol),The temperature was raised to 90 C and the reaction was stirred for 8.0 h. The reaction solution was cooled to 25 C.A large amount of yellow solid precipitated in the solution and was suction filtered.A large amount of crude yellowish brown product was obtained.The crude product was recrystallized from acetonitrile (50 mL).6.7 g of a yellow solid were obtained.Yield: 54%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.3% | With N-ethyl-N,N-diisopropylamine; In ethanol; at 90℃; for 8.0h; | At 25 C,The compound <strong>[83410-15-5]4-chloro-5-iodo-6-methylpyrimidine</strong> (6.61 g, 14.13 mmol) and the compound 1-(3-fluorobenzyl)-1H-indazole-5-amine (3.41 g, 14.13 mmol) Soluble in ethanol (300mL),Diisopropylethylamine (9.18 g, 70.65 mmol) was slowly added.Slowly heat up to 90 C for 8.0 h. Concentrate the reaction solution,Obtained a reddish brown oil which was dissolved in dichloromethane (200 mL).The organic phase was washed once with saturated brine (50 mL).Dry anhydrous sodium sulfate (20g), concentrated,The residue is subjected to column chromatography (eluent:DCM / MeOH (v / v) = 20/1) gave 4.02 g of brown solid.Yield: 62.3% |
Tags: 202197-31-7 synthesis path| 202197-31-7 SDS| 202197-31-7 COA| 202197-31-7 purity| 202197-31-7 application| 202197-31-7 NMR| 202197-31-7 COA| 202197-31-7 structure
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Code | Phrase |
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P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
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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. |
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P282 | Wear cold insulating gloves/face shield/eye protection. |
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Response | |
Code | Phrase |
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P306 | IF ON CLOTHING: |
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P321 | |
P322 | |
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P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
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P378 | |
P380 | Evacuate area. |
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P390 | Absorb spillage to prevent material damage. |
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P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
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P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
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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: |
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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. |
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P411 | |
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Disposal | |
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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 |
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H223 | Flammable aerosol |
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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 |
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H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
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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 |
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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.
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