* 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.
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,4-dioxane; water at 50℃; Inert atmosphere
Combine l-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)phenyl)urea (25.9 g, 68.5 mmol), 7-methyl-2-(methylamino)pyrido[2,3- d]pyrimidin-6-yl trifluoromethanesulfonate (22.09 g, 68.5 mmol), and NaHC03 (17.28 g, 206 mmol) in 1,4-dioxane (500 mL) and water (125 mL) and sparge with argon for 20 minutes. Add tetrakis(triphenylphosphine)palladium (3.96 g, 3.43 mmol) and then heat under argon at 50 °C. Add additional portion of 7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (300 mg, 0.55 mmol) and continue heating at 50 °C overnight. Cool the mixture to RT, collect the solid by filtration, and wash with water then diethyl ether. Treat the solid with acetonitrile (50 mL) and heat the slurry at 80 °C for 30 minutes. Collect the solid by filtration, wash with acetonitrile and dry under vacuum at 80 °C to obtain a pale yellow solid. Treat the solid with MeOH (50 mL), and heat the mixture at 80 °C for 1 hour. Cool to RT, collect the solid via filtration, wash with MeOH (20 mL), and dry under vacuum to obtain the title compound (22.5 g, 77percent yield) as a pale yellow solid. MS (m/z): 425.2 (M+l).
Reference:
[1] Patent: WO2013/134243, 2013, A1, . Location in patent: Page/Page column 22-23
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
2
[ 1454682-74-6 ]
[ 1454682-79-1 ]
[ 1454682-72-4 ]
Yield
Reaction Conditions
Operation in experiment
70%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 85℃; Inert atmosphere
Method B: Sparge a suspension of l-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)urea (4.48 g, 11.8 mmol), 6-bromo-N,7- dimethylpyrido[2,3-d]pyrimidin-2-amine (3.0 g, 11.8 mmol) and K2CO3 (4.91 g, 35.6 mmol) in dioxane (80 mL) and water (20 mL) with argon, treat with tetrakis(triphenylphosphine)palladium (0.685 g, 0.593 mmol) and heat at 85 °C overnight. Remove the dioxane under reduced pressure, treat the mixture with EtOAc and brine, separate the layers, dry the organics over Na2S04, concentrate and purify by silica gel chromatography (40percent to 100percent EtOAc/hexane, 100percent EtOAc, 5percent MeOH/ EtOAc). Treat the material with CH3CN, heat at 80°C for 1 hour, cool to RT and collect the solid via filtration to afford the title compound (3.52 g, 70percent> yield) as a pale yellow solid. MS (m z): 425.2 (M+l).
Reference:
[1] Patent: WO2013/134243, 2013, A1, . Location in patent: Page/Page column 22-23
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
3
[ 1012880-11-3 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Patent: WO2013/134243, 2013, A1,
[4] Patent: WO2013/134243, 2013, A1,
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[6] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[7] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[8] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
4
[ 1454682-73-5 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[6] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
5
[ 945244-29-1 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Patent: WO2013/134243, 2013, A1,
[4] Patent: WO2013/134243, 2013, A1,
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[6] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[7] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[8] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
6
[ 776-53-4 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[6] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
7
[ 5909-24-0 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[6] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
8
[ 452-63-1 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Patent: WO2013/134243, 2013, A1,
[4] Patent: WO2013/134243, 2013, A1,
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[6] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[7] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[8] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
9
[ 170098-98-3 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Patent: WO2013/134243, 2013, A1,
[4] Patent: WO2013/134243, 2013, A1,
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[6] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[7] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[8] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
10
[ 588-36-3 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
11
[ 770-31-0 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Patent: WO2013/134243, 2013, A1,
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
12
[ 1454682-75-7 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
13
[ 1454682-76-8 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
14
[ 1454682-78-0 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
15
[ 1256347-64-4 ]
[ 1454682-72-4 ]
Reference:
[1] Patent: WO2013/134243, 2013, A1,
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
16
[ 2987-16-8 ]
[ 1454682-72-4 ]
Reference:
[1] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
17
[ 30564-98-8 ]
[ 1454682-72-4 ]
Reference:
[1] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 10, p. 4165 - 4179
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In 1,4-dioxane; water; at 50.0℃;Inert atmosphere;
Combine l-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)phenyl)urea (25.9 g, 68.5 mmol), 7-methyl-2-(methylamino)pyrido[2,3- d]pyrimidin-6-yl trifluoromethanesulfonate (22.09 g, 68.5 mmol), and NaHC03 (17.28 g, 206 mmol) in 1,4-dioxane (500 mL) and water (125 mL) and sparge with argon for 20 minutes. Add tetrakis(triphenylphosphine)palladium (3.96 g, 3.43 mmol) and then heat under argon at 50 C. Add additional portion of 7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (300 mg, 0.55 mmol) and continue heating at 50 C overnight. Cool the mixture to RT, collect the solid by filtration, and wash with water then diethyl ether. Treat the solid with acetonitrile (50 mL) and heat the slurry at 80 C for 30 minutes. Collect the solid by filtration, wash with acetonitrile and dry under vacuum at 80 C to obtain a pale yellow solid. Treat the solid with MeOH (50 mL), and heat the mixture at 80 C for 1 hour. Cool to RT, collect the solid via filtration, wash with MeOH (20 mL), and dry under vacuum to obtain the title compound (22.5 g, 77% yield) as a pale yellow solid. MS (m/z): 425.2 (M+l).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 85.0℃;Inert atmosphere;
Method B: Sparge a suspension of l-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)urea (4.48 g, 11.8 mmol), 6-bromo-N,7- dimethylpyrido[2,3-d]pyrimidin-2-amine (3.0 g, 11.8 mmol) and K2CO3 (4.91 g, 35.6 mmol) in dioxane (80 mL) and water (20 mL) with argon, treat with tetrakis(triphenylphosphine)palladium (0.685 g, 0.593 mmol) and heat at 85 C overnight. Remove the dioxane under reduced pressure, treat the mixture with EtOAc and brine, separate the layers, dry the organics over Na2S04, concentrate and purify by silica gel chromatography (40% to 100% EtOAc/hexane, 100% EtOAc, 5% MeOH/ EtOAc). Treat the material with CH3CN, heat at 80C for 1 hour, cool to RT and collect the solid via filtration to afford the title compound (3.52 g, 70%> yield) as a pale yellow solid. MS (m z): 425.2 (M+l).