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

HRID 1500005Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[CH:6][CH:7]=1.[NH2:10][C:11]1[C:16]([F:17])=[CH:15][N:14]=[C:13](Cl)[N:12]=1>CC(O)(C)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][O:9][C:13]1[N:12]=[C:11]([NH2:10])[C:16]([F:17])=[CH:15][N:14]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a magnetically stirred mixture of t-BUOK (1.0 M in t-BuOH, 1.36 ml, 1.36 mmol) was added (3-bromophenyl)methanol (0.25 g, 1.36 mmol). To the resulting solution was added 4-amino-2-chloro-5-fluoropyrimidine (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 a 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 a vacuum oven
washeluted with CH2Cl2
customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record: ord-4ab0895db2754391bbce2cef4730a850
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09204653B2

Reaction notes

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