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CAS No. : | 1023595-17-6 | MDL No. : | MFCD09878901 |
Formula : | C7H7BN2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | BGZZJZIZRARGGZ-UHFFFAOYSA-N |
M.W : | 161.95 | Pubchem ID : | 44118310 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
Example 201Preparation of: EPO <DP n="226"/>A mixture of 4-indazole-boronic acid (17 mg, 0.07 mmol), (24 mg, 0.05 mmol), Pd(Ph3P)4, K2co3 (22 mg) in a 3:1 mixture of dioxane/H2O (1 ml_) was heated at 150 0C for 30 minutes by microwave. The mixture was cooled, concentrated and then treated with a 9:1 mixture of TFA/hfeO at rt for 2h and then concentrated. The residue was taken up into 3:1 mixture of DMSO/CH3CN and purified by preparative LC to provide the title compound as TFA salt. HPLC-MS RT= 1.72 minutes, mass calculated for formula C20Hi9N7OS 405.14, observed LCMS m/z 406.15 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate;trans-bis(triphenylphosphine)palladium dichloride; In water; acetonitrile; at 150℃; for 0.25h;Microwave irradiation; | Example 72; 4-(5-(lH-indazol-4-yl)-2-(methylthio)thiazolo[4,5-d]pyrimidin-7- yl)morpholine 147[00404] 5-Chloro-7-morpholino-2-(thiazol-4-yl)thiazolo[4,5-d]pyrimidine , lH-indazol-4- yl-4-boronic acid (2.5 eq), and trans-dichlorobis(triphenylphosphine)palladium(II) (0.1 eq) were <n="100"/>slurried with equal parts IM potassium acetate (3 eq) and acetonitrile. The solution was microwaved at 150 C for 15 minutes. The solution filtered and the solution was dried in vacuo. The resulting residue was purified by reverse phase silica gel chromatography to give the product 147. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In water; acetonitrile; at 130℃; for 0.633333h;Microwave irradiation; | 5-Chloro-2-((4-methylsulfonylpiperazin- 1 -yl)methyl)-7-moipholinothiazolo[5,4- d]pyrimidine, lH-indazol-4-yl-4-boronic acid (1.2 eq), and trans- dichlorobis(triphenylphosphine)palladium(II) (0.1 eq) were combined in a solution of equal parts sodium carbonate aqueous solution (IM, 3 eq) and acetonitrile. The solution was microwaved at 1300C for eighteen minutes. An additional 0.1 equivalents of trans- dichlorobis(triphenylphosphine)palladium(II) was added and the solution was microwaved at130 0C for an additional twenty minutes. Acetonitrile was added and the solution was filtered.The organic layer was purified by reverse phase chromatography to give the off white solid of129. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In water; acetonitrile; at 140℃; for 0.166667h;Microwave irradiation; | (5-Chloro-7-morpholinothiazolo[4,5-d]pyrimidin-2-yl)(4- methylsulfonylpiperazin-l-yl)methanone, lH-indazol-4-yl-4-boronic acid (2.5 eq), and trans- dichlorobis(triphenylphosphine)palladium(II) (0.1 eq) were slurried with equal parts IM sodium carbonate aqueous solution (3 eq) and acetonitrile. The solution was microwaved at 140 C for 10 minutes. Water was added and the solution was filtered. The resulting precipitate was washed with methylene chloride and the organic layer was purified by silica gel chromatography followed by reverse phase silica gel chromatography to give the product 141. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 100℃; for 3h;Sealed tube; | Step i; A mixture of 57 (2.09 g, 5.00 mmol), 1 H-indazol-4-ylboronic acid (1.21 g, 7.50 mmol), Pd(PPh3^CI2 (213 mg, 0.30 mmol), and K2CO3 (2.07 g, 15.0 mmol) in dioxane/water (20/10 ml_) was bubbled with nitrogen for 5 minutes. The reaction mixture was then heated in a sealed tube at 100 C to give a brown solution, which turned to a gray suspension later. Heating was continued for 3 h. After cooling the mixture was diluted with water (50 ml_) and vigorously stirred. The solid was collected by vacuum-filtration and further dried to give 2.49 g (99%) of 89 as a yellow solid. 1H NMR (400 MHz, CDCI3) delta 1.48 (s, 9 H), 1.94 (d, J=6.32 Hz, 2 H), 2.84 (br s, 4 H), 3.63 (s, 3 H), 4.31 (br s, 2 H), 6.33 (br s, 1 H), 7.56 - 7.63 (m, 1 H), 7.64 - 7.70 (m, 1 H), 7.74 (d, J=7.07 Hz, 1 H), 8.12 (d, J=8.84 Hz, 1 H), 8.45 - 8.66 (m, 2 H), 8.78 (s, 1 H), 10.44 (br s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 90℃;Sealed tube; | Step 3; A mixture of 1 -(1-acetylpiperidin-4-yl)-8-chloro-3-methyl-1 /-/-imidazo[4,5- c][1 ,5]naphthyridin-2(3H)-one (93) (540 mg, 1.50 mmol), 1 H-indazol-4-ylboronic acid (364 mg, 2.25 mmol), Pd(PPh3)2CI2 (74.4 mg, 0.105 mmol), and K2CO3 (622 mg, 4.50 mmol) in dioxane/water (8/4 ml_) was bubbled with nitrogen for 5 minutes, and heated in a sealed tube at 90 C overnight. After cooling the reaction mixture was partitioned between water (40 ml_) and CH2CI2/MeOH (100/5 ml_). The aqueous layer was further extracted with CH2CI2 (50 ml_). The organic extract was washed with brine, dried over sodium sulfate, and concentrated to give a waxy, yellow solid, which was purified on ISCO purification system with a 40-gram column using 0 - 10% MeOH in CH2CI2 to afford 450 mg (68%) of the title compound 254 as a waxy, pale yellow solid. 1H NMR (400 MHz, CDCI3) delta 1.88 - 2.04 (m, 2 H), 2.08 (br s, 3 H), 2.62 (t, J=12.51 Hz, 1 H), 2.82 (br s, 1 H), 3.02 (br s, 1 H), 3.24 (t, J=12.25 Hz, 1 H), 3.64 (s, 3 H), 3.95 (d, J=13.14 Hz, 1 H), 4.85 (d, J=12.88 Hz, 1 H), 6.28 (br s, 1 H), 7.54 - 7.64 (m, 1 H), 7.70 (t, J=7.20 Hz, 2 H), 8.12 (d, J=8.84 Hz, 1 H), 8.56 (d, J=8.84 Hz, 2 H), 8.79 (s, 1 H), 11.02 (br s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 12h; | Intermediate 22: Methyl 2-(1 H-lndazol-4-yl)-8-thiomethyl-4-morpholin-4-yl-pyridor3,2- dlpyrimidine-6-carboxylateA suspension of Example 2 (200 mg; 0.56 mmol), <strong>[1023595-17-6]indazole-4-boronic acid</strong> (180 mg; 1.12 mmol), Pd(PPh3)4 (64 mg; 0.06 mmol), sodium carbonate (170 mg; 1.6 mmol) in dioxane (12 ml.) and water (12 mL) was stirred at 900C for 12 hours, filtered through a short plug of Celite then concentrated in vacuo to afford the title compound as a yellow solid which was used without further purification. HPLC (Method C): RT 2.47 min (purity 68%). MS (ES+): 437.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | With PdPCy3; sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 0.5h;Inert atmosphere; Microwave irradiation; | General procedure: The chloropyrimidine (1.0 equiv), boronic acid or ester (2.2 equiv), Bedford catalyst 29 (0.05 equiv) and 2 M aqueous Na2CO3 (2.2 equiv) were dissolved in 1,2-DME. The solution was degassed and backfilled with nitrogen, then stirred with microwave heating at 150 C for 30 min. The reaction mixture was cooled, absorbed onto a plug of silica (100 mg) and eluted (CHCl3/MeOH, 9:1). The crude product was obtained by evaporating the filtrate in vacuo and purified by one of the following methods:Method A: The crude compound was dissolved in methanol and purified using an SCX-2 ion exchange column, eluting first with MeOH, then 2 M NH3 in MeOH.Method B: Purification by preparative TLC using the specified eluent.Method C: Recrystallisation from MeOH/CHCl3/hexane, 1:1:4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With PdPCy3; sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 0.5h;Inert atmosphere; Microwave irradiation; | General procedure: The chloropyrimidine (1.0 equiv), boronic acid or ester (2.2 equiv), Bedford catalyst 29 (0.05 equiv) and 2 M aqueous Na2CO3 (2.2 equiv) were dissolved in 1,2-DME. The solution was degassed and backfilled with nitrogen, then stirred with microwave heating at 150 C for 30 min. The reaction mixture was cooled, absorbed onto a plug of silica (100 mg) and eluted (CHCl3/MeOH, 9:1). The crude product was obtained by evaporating the filtrate in vacuo and purified by one of the following methods:Method A: The crude compound was dissolved in methanol and purified using an SCX-2 ion exchange column, eluting first with MeOH, then 2 M NH3 in MeOH.Method B: Purification by preparative TLC using the specified eluent.Method C: Recrystallisation from MeOH/CHCl3/hexane, 1:1:4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With PdPCy3; sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 0.5h;Inert atmosphere; Microwave irradiation; | General procedure: The chloropyrimidine (1.0 equiv), boronic acid or ester (2.2 equiv), Bedford catalyst 29 (0.05 equiv) and 2 M aqueous Na2CO3 (2.2 equiv) were dissolved in 1,2-DME. The solution was degassed and backfilled with nitrogen, then stirred with microwave heating at 150 C for 30 min. The reaction mixture was cooled, absorbed onto a plug of silica (100 mg) and eluted (CHCl3/MeOH, 9:1). The crude product was obtained by evaporating the filtrate in vacuo and purified by one of the following methods:Method A: The crude compound was dissolved in methanol and purified using an SCX-2 ion exchange column, eluting first with MeOH, then 2 M NH3 in MeOH.Method B: Purification by preparative TLC using the specified eluent.Method C: Recrystallisation from MeOH/CHCl3/hexane, 1:1:4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With PdPCy3; sodium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 0.5h;Inert atmosphere; Microwave irradiation; | General procedure: The chloropyrimidine (1.0 equiv), boronic acid or ester (2.2 equiv), Bedford catalyst 29 (0.05 equiv) and 2 M aqueous Na2CO3 (2.2 equiv) were dissolved in 1,2-DME. The solution was degassed and backfilled with nitrogen, then stirred with microwave heating at 150 C for 30 min. The reaction mixture was cooled, absorbed onto a plug of silica (100 mg) and eluted (CHCl3/MeOH, 9:1). The crude product was obtained by evaporating the filtrate in vacuo and purified by one of the following methods:Method A: The crude compound was dissolved in methanol and purified using an SCX-2 ion exchange column, eluting first with MeOH, then 2 M NH3 in MeOH.Method B: Purification by preparative TLC using the specified eluent.Method C: Recrystallisation from MeOH/CHCl3/hexane, 1:1:4. |
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