Sodium Bicarbonate → 4-[7-(1-cyclopentyl-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroisoquinolin-2(1H)-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine
Reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH:7]([CH3:26])[N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.[CH:27]1([N:32]2[CH:36]=[C:35](B3OC(C)(C)C(C)(C)O3)[CH:34]=[N:33]2)[CH2:31][CH2:30][CH2:29][CH2:28]1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:27]1([N:32]2[CH:36]=[C:35]([C:2]3[CH:11]=[C:10]4[C:5]([CH2:6][CH:7]([CH3:26])[N:8]([C:12]5[CH:17]=[C:16]([N:18]6[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]6)[N:15]=[C:14]([NH2:25])[N:13]=5)[CH2:9]4)=[CH:4][CH:3]=3)[CH:34]=[N:33]2)[CH2:31][CH2:30][CH2:29][CH2:28]1Participants
8
Reactant 3
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 90 °C
Procedure
A mixture of 4-(7-bromo-3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (10 mg, 0.02 mmol; Peak 1, Example 49, Step 7), 1-cyclopentyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (7.5 mg, 0.029 mmol), tetrakis(triphenylphosphine)palladium(0) (1.4 mg, 0.0012 mmol), and sodium bicarbonate (6.0 mg, 0.072 mmol) in 1,4-dioxane (0.2 mL) and water (0.1 mL) was stirred at 90° C. overnight. After cooling, it was diluted with methanol, and purified with RP-HPLC (pH=10) to afford the desired product (4.7 mg). LCMS (M+H)+: m/z=473.2.
Workup
- temperatureAfter cooling
- custompurified with RP-HPLC (pH=10)
Sources & evidence
- ORD record
- ord-866bf0a8bcc1484fb68c2cb879c420c4
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08436008B2
Reaction notes
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