3-Bromo-5-methylaniline → HCID 118216481, compound

HRID 595169Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH:8]([F:10])[F:9])[C:5]([F:11])=[CH:4][N:3]=1.[Br:12][C:13]1[CH:14]=[C:15]([CH:17]=[C:18]([CH3:20])[CH:19]=1)[NH2:16]>O1CCOCC1>[Br:12][C:13]1[CH:14]=[C:15]([NH:16][C:2]2[N:7]=[C:6]([CH:8]([F:10])[F:9])[C:5]([F:11])=[CH:4][N:3]=2)[CH:17]=[C:18]([CH3:20])[CH:19]=1

Participants

Conditions

Temperature: 105 °C

Procedure

2-Chloro-4-(difluoromethyl)-5-fluoropyrimidine (30 g, 162 mmol, 1.00 equiv) p-TsOH (37 g, 215 mmol, 1.33 equiv), 1,4-dioxane (600 mL), 3-bromo-5-methylaniline (46 g, 247 mmol, 1.53 equiv) were added into a 1000-mL pressure tank reactor purged and maintained with an inert atmosphere of nitrogen. The resulting solution was stirred for 72 h at 105° C. The reaction mixture was cooled to room temperature. The solid was filtered out and the filtrate was concentrated under reduced pressure. The residue was applied onto a silica gel and purified column chromatography on silica (1:20 ethyl acetate/petroleum ether) to afford N-(3-bromo-5-methylphenyl)-4-(difluoromethyl)-5-fluoropyrimidin-2-amine as a yellow solid. MS ESI calc'd. for C12H10BrF3N3 [M+H]+332/334. found 332/334. 1H NMR (400 MHz, CDCl3): δ 8.45 (1H, s), 7.73 (1H, s), 7.21 (1H, s), 7.18 (1H, s), 7.05 (1H, s), 6.63 (1H, t, J=53.37 Hz), 2.34 (3H, s).

Workup

custompurged
temperaturemaintained with an inert atmosphere of nitrogen
temperatureThe reaction mixture was cooled to room temperature
filtrationThe solid was filtered out
concentrationthe filtrate was concentrated under reduced pressure
custompurified column chromatography on silica (1:20 ethyl acetate/petroleum ether)

Sources & evidence

ORD record: ord-078af239ba164554a3fe2a7f007a542b
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242984B2

Reaction notes

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