4-Aminophenethyl alcohol → 2-(4-((2-(Cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)amino)phenyl)ethanol

HRID 1508902Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([O:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[N:3]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][OH:27])=[CH:21][CH:20]=1>CN1C(=O)CCC1.O>[CH:13]1([O:12][C:4]2[N:3]=[C:2]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][OH:27])=[CH:21][CH:20]=3)[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

Conditions

Temperature: 120 °C

Procedure

A 10-mL microwave vial was charged with 4-chloro-2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidine (0.090 g, 0.34 mmol) and (4-aminophenyl)ethyl alcohol (0.069 g, 0.51 mmol) in NMP (3 mL). The resulting mixture was heated at 120° C. under microwave irradiation for 1 h. After this time, the reaction mixture was cooled and diluted with water (50 mL) affording a solid. The solid was isolated by filtration and chromatography on silica using hexanes/ethyl acetate (10:0 to 0:10) as eluent to afford the title compound (0.087 g, 70%) as a white solid. MW=367.37. M.p. 173-175° C. 1H NMR (DMSO-d6, 500 MHz) δ 10.01 (s, 1H), 7.56 (br d, J=7.0 Hz, 2H), 7.22 (d, J=8.5 Hz, 2H), 6.73 (s, 1H), 5.30 (septet, J=3.0 Hz, 1H), 4.61 (t, J=5.0 Hz, 1H), 3.62-3.57 (m, 2H), 2.70 (t, J=7.0 Hz, 2H), 2.00-1.90 (m, 2H), 1.80-1.66 (m, 4H), 1.65-1.55 (m, 2H); APCI MS m/z 368 [M+H]+.

Workup

temperatureAfter this time, the reaction mixture was cooled
customaffording a solid
customThe solid was isolated by filtration and chromatography on silica

Sources & evidence

ORD record: ord-abc2aa86b9744a3290398b2eef179fa9
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

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