Sodium hydride → 4-(6-Bromo-5-fluoro-3-methylindazol-1-yl)pyrimidin-2-amine

HRID 1398619Notes

Reaction equation

[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:11])=[N:7][NH:8]2)=[CH:4][C:3]=1[F:12].[H-].[Na+].Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([NH2:22])[N:17]=1>CN(C=O)C>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:11])=[N:7][N:8]2[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH2:22])[N:17]=2)=[CH:4][C:3]=1[F:12]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 6-bromo-5-fluoro-3-methyl-1H-indazole (130 mg, 0.284 mmol, 50% purity) in DMF (2 ml) was added NaH (60% oil dispersion, 18.16 mg, 0.454 mmol) at 0° C. The reaction mixture stirred for 15 minutes before the slow addition of a solution of 4-chloropyrimidin-2-amine (73.53 mg, 0.568 mmol) in DMF (2 mL). The resulting mixture was stirred at 60° C. for 16 hr. The reaction mixture was cooled and partitioned between water (15 ml) and EtOAc (15 ml). A precipitate formed and was collected by suction filtration. The filtrate was concentrated in vacuo and purified by flash chromatography (Isolute column, 1-2% methanol in DCM) to give the title intermediate as a yellow oil: 1H NMR (500 MHz, DMSO) delta 2.56 (3H, s), 7.00 (1H, s), 7.04-7.14 (2H, m), 7.92 (1H, d, J=8.35 Hz), 8.26 (1H, d, J=5.52 Hz), 9.22 (1H, d, J=5.99 Hz); LC-MS: m/z=+321.90, 323.80 (M+H)+.

Workup

temperatureThe reaction mixture was cooled
custompartitioned between water (15 ml) and EtOAc (15 ml)
customA precipitate formed
filtrationwas collected by suction filtration
concentrationThe filtrate was concentrated in vacuo
custompurified by flash chromatography (Isolute column, 1-2% methanol in DCM)

Sources & evidence

ORD record: ord-01625706641246618aa9ed6997d1604b
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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