Triethylamine → HCID 86629366, compound
Reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[C:4]2[N:9]([CH3:12])[N:10]=[CH:11][C:3]=12.CCN(CC)CC.Cl.[CH:21]12[O:28][CH:25]([O:26][CH2:27]1)[CH2:24][NH:23][CH2:22]2>C(Cl)Cl>[Cl:8][C:6]1[N:5]=[C:4]2[N:9]([CH3:12])[N:10]=[CH:11][C:3]2=[C:2]([N:23]2[CH2:24][CH:25]3[O:28][CH:21]([CH2:27][O:26]3)[CH2:22]2)[N:7]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
4,6-Dichloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (0.5 g, 2.46 mmol), Et3N (1.05 mL, 7.5 mmol) and 6,8-dioxa-3-azabicyclo[3.2.1]octane hydrochloride (373 mg) in CH2Cl2 (5 mL) is stirred for 18 h. Concentration in vacuo followed by silica gel chromatography (hexane/ethyl acetate) gives 3-(6-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-6,8-dioxa-3-azabicyclo[3.2.1]octane as a white powder (320 mg). This material (0.16 g, 0.57 mmol) was treated with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.186 g, 0.85 mmol), aq. Na2CO3 (0.425 mL, 2M), and tetrakis triphenylphosphine palladium (20 mg) in 1:1 toluene:ethanol. The reaction mixture was heated in a microwave at 120 C for 20 min to give 4-(4-(6,8-dioxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline. To this material (190 mg, 0.56 mmol) in CH2Cl2 is added Et3N (0.42 mL) and a solution of triphosgene (83 mg, 0.28 mmol) in CH2Cl2. After 30 min half of the solution is added to 3-aminopyridine (105 mg, 1.12 mmol). After 2 h aq. workup and silica gel chromatography (EtOAc/MeOH) gives the title compound as an off-white solid (104 mg). HRMS m/z=459.1894 (M+H).
Workup
- concentrationConcentration in vacuo
Sources & evidence
- ORD record
- ord-ab034226815741e8b61f6da717d24aab
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08129371B2
Reaction notes
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