Piperidine → 1-(2-aminopyrimidin-4-yl)-N,N-dimethyl-6-[2(trimethylsily)ethynyl]indazole-3-carboxamide

HRID 1398596Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=3)[C:10]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1.[C:23]([Si:25]([CH3:28])([CH3:27])[CH3:26])#[CH:24].N1CCCCC1>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.[Cu]I>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:24]#[C:23][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:15]=3)[C:10]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a mixture of 1-(2-aminopyrimidin-4-yl)-6-bromo-N,N-dimethylindazole-3-carboxamide (61-b) (500 mg, 1.27 mmol), tetrakis(triphenylphosphine)palladium (118 mg, 0.102 mmol), copper(I) iodide (19.4 mg, 0.102 mmol) and ethynyl(trimethyl)silane 0.39 ml, 2.54 mmol) was added piperidine (3.1 mL). The mixture was purged with nitrogen for 2 minutes and then stirred at 65° C. for 4 hr. The reaction mixture was concentrated in vacuo, DCM (5 mL) was added and the concentration repeated (×2). The crude product was purified by flash chromatography (Biotage, 2-8% methanol in DCM) to give the title intermediate (250 mg): LC-MS: m/z=+379.45 (M+H)+.

Workup

customThe mixture was purged with nitrogen for 2 minutes
concentrationThe reaction mixture was concentrated in vacuo, DCM (5 mL)
additionwas added
concentrationthe concentration
customThe crude product was purified by flash chromatography (Biotage, 2-8% methanol in DCM)

Sources & evidence

ORD record: ord-3fddb2fe225347519da64a3049c82b68
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

Loading…