Piperidine → 4-{3-Methyl-6-[2-(trimethylsilyl)ethynyl]indazol-1-yl}pyrimidin-2-amine

HRID 1398553Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:18])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)=[CH:4][CH:3]=1.N1CCCCC1.[C:25]([Si:27]([CH3:30])([CH3:29])[CH3:28])#[CH:26]>[Cu]I>[CH3:18][C:6]1[C:5]2[C:9](=[CH:10][C:2]([C:26]#[C:25][Si:27]([CH3:30])([CH3:29])[CH3:28])=[CH:3][CH:4]=2)[N:8]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)[N:7]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a pressure tube was added 4-(6-bromo-3-methylindazol-1-yl)pyrimidin-2-amine (0.5 g, 1.64 mmol), piperidine (3.5 mL) tetrakis(triphenylphosphine)palladium (113.98 mg, 0.1 mmol), copper(I) iodide (18.79 mg, 0.1 mmol) and ethynyl(trimethyl)silane (0.47 ml, 3.29 mmol). The mixture was purged with nitrogen for 2 minutes and then stirred at 65° C. for 1.5 hr. The reaction mixture was concentrated in vacuo, DCM (5 mL) was added and the concentration repeated (×2). The mixture was purified by column chromatography (Biotage, 3-8% MeOH gradient in DCM) to give the title intermediate as a white solid (116 mg): 1H NMR (250 MHz, DMSO) delta 0.28 (9H, s), 2.57 (3H, s), 7.03 (3H, d, J=5.5), 7.38 (1H, d, J=8.2), 7.84 (1H, d, J=8.2), 8.26 (1H, d, J=5.5), 8.90 (1H, s); LC-MS: m/z=+322.50 (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 mixture was purified by column chromatography (Biotage, 3-8% MeOH gradient in DCM)

Sources & evidence

ORD record: ord-dffce8a8b01b4edc83853eb6173ce998
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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