Chloromethyl ethyl ether → HCID 58166474, compound

HRID 1405983Notes

Reaction equation

[F:1][C:2]1[C:3]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[N:4][C:5]([OH:8])=[N:6][CH:7]=1.Cl[CH2:19][O:20][CH2:21][CH3:22]>CC#N>[CH2:21]([O:20][CH2:19][N:6]1[CH:7]=[C:2]([F:1])[C:3]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[N:4][C:5]1=[O:8])[CH3:22]

Participants

Conditions

Temperature: 65 °C

Procedure

A 25 mL screw-top vial was charged with 5-fluoro-4-(2-fluorobenzylamino)pyrimidin-2-ol (49.7 mg, 0.210 mmol), CH3CN (1 mL), and BSA (0.054 mL, 0.0221 mmol), and the mixture was agitated on an rotary shaker at 65° C. for 30 min. After cooling to room temperature, (chloromethoxy)ethane (0.022 mL, 0.237 mmol) was added, and the resulting mixture was agitated on a rotary shaker at room temperature for 16 h. The crude reaction mixture was concentrated in vacuo and was purified by normal phase chromatography (gradient, 0 to 25% MeOH/CH2Cl2) to afford 1-(ethoxymethyl)-5-fluoro-4-(2-fluorobenzylamino)-pyrimidin-2(1H)-one (55.0 mg, 89%) as a yellow oil: 1H NMR (400 MHz, DMSO-d6) δ 8.60 (t, J=5.8 Hz, 1H), 8.05-7.95 (m, 1H), 7.40-7.26 (m, 2H), 7.26-7.10 (m, 2H), 5.01 (s, 2H), 4.59 (d, J=5.9 Hz, 2H), 3.49 (q, J=7.0 Hz, 2H), 1.09 (dd, J=9.0, 5.0 Hz, 3H); ESIMS m/z 296 ([M+H]+), m/z 294 ([M−H]−).

Workup

temperatureAfter cooling to room temperature
stirringthe resulting mixture was agitated on a rotary shaker at room temperature for 16 h
customThe crude reaction mixture
concentrationwas concentrated in vacuo
customwas purified by normal phase chromatography (gradient, 0 to 25% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-8c8b6875d3af4c5d8ea202e1d21fb36f
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08916579B2

Reaction notes

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