3-Bromobenzyl alcohol → 2-(3-Bromobenzyloxy)-5-fluoropyrimidin-4-ylamine

HRID 705558Notes

Reaction equation

CC([O-])(C)C.[K+].[Br:7][C:8]1[CH:9]=[C:10]([CH2:14][OH:15])[CH:11]=[CH:12][CH:13]=1.Cl[C:17]1[N:22]=[C:21]([NH2:23])[C:20]([F:24])=[CH:19][N:18]=1>O>[Br:7][C:8]1[CH:9]=[C:10]([CH:11]=[CH:12][CH:13]=1)[CH2:14][O:15][C:17]1[N:22]=[C:21]([NH2:23])[C:20]([F:24])=[CH:19][N:18]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a magnetically stirred mixture of KOtBu (1.0 M in tBuOH, 1.36 ml, 1.36 mmol) was added (3-bromophenyl)methanol (0.25 g, 1.36 mmol). To the resulting solution was added 2-chloro-5-fluoropyrimidine-4-ylamine (0.10 g, 0.68 mmol) and the mixture was capped and stirred at 90° C. for 4 h. The reaction mixture was cooled to room temperature, diluted with water, and the resulting precipitate was collected by filtration. The solid was washed with water, washed with cyclohexane, and dried in the vacuum oven. A CH2Cl2 solution of the compound was loaded onto Biotage SCX column and eluted with CH2Cl2 followed by 2.0 M NH3 in MeOH. The solvent was evaporated under reduced pressure to give the title compound (0.100 g, 49%) as an off-white solid: mp 143-145° C.; 1H NMR (400 MHz, DMSO-d6) δ 7.90 (d, J=2.5 Hz, 1H), 7.61 (s, 1H), 7.43 (d, J=8.0 Hz, 1H), 7.36 (d, J=7.7 Hz, 1H), 7.22 (t, J=7.7 Hz, 1H), 5.28 (s, 2H), 5.20 (br s, 2H); GCMS (EI) m/z 297, 299 (M)+.

Workup

customthe mixture was capped
temperatureThe reaction mixture was cooled to room temperature
filtrationthe resulting precipitate was collected by filtration
washThe solid was washed with water
washwashed with cyclohexane
customdried in the vacuum oven
washeluted with CH2Cl2
customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record: ord-974a0a9392874bb184fb5a37f029953f
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174970B2

Reaction notes

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