Water → 2-{(2S)-3-cyclohexyl-2-[5-(1-methyl-1H-pyrazol-5-yl)-1-oxo-1,3-dihydro-2H-isoindol-2-yl]propyl}-1H-isoindole-1,3(2H)-dione
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([C@@H:12]([CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[CH2:13][N:14]1[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]1=[O:24])[CH2:5]2.[CH3:32][N:33]1[C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][CH:35]=[N:34]1.C(N(CC)C(C)C)(C)C.O1CCOCC1.O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:26]1([CH2:25][C@H:12]([N:6]2[CH2:5][C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:37]4[N:33]([CH3:32])[N:34]=[CH:35][CH:36]=4)[CH:3]=3)[C:7]2=[O:11])[CH2:13][N:14]2[C:15](=[O:24])[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:22]2=[O:23])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1Participants
7
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 110 °C
Procedure
A mixture of 2-[(2S)-2-(5-bromo-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dione (103.5 mg, 0.2151 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (47 mg, 0.23 mmol), N,N-diisopropylethylamine (0.11 mL, 0.63 mmol), and bis(tri-t-butylphosphine)palladium (0.011 g, 0.021 mmol) in 1,4-dioxane (4 mL, 50 mmol) and water (0.2 mL, 10 mmol) was stirred at 110° C. for 40 min under microwave irradiation. Direct purification on prep.—HPLC afforded 30 mg (29% yield) of the desired intermediate. LC-MS found: 483.1 (M+H)+.
Workup
- customDirect purification
Sources & evidence
- ORD record
- ord-b6703cced08d4c8c873d91a2426abfd0
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08895571B2
Reaction notes
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