2-(4-(4-Chloro-3-(trifluoromethyl)phenoxy)phenyl)ethanamine → 2-{2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamino}-5-methyl-1H-pyrimidin-4-one

HRID 474879

Reaction equation

HRID 474879 reaction equation
[CH3:1][C:2]1[C:3](=[O:10])[N:4]=[C:5](SC)[NH:6][CH:7]=1.[Cl:11][C:12]1[CH:27]=[CH:26][C:15]([O:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][NH2:25])=[CH:19][CH:18]=2)=[CH:14][C:13]=1[C:28]([F:31])([F:30])[F:29]>C(O)C>[Cl:11][C:12]1[CH:27]=[CH:26][C:15]([O:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][NH:25][C:5]3[NH:6][CH:7]=[C:2]([CH3:1])[C:3](=[O:10])[N:4]=3)=[CH:19][CH:18]=2)=[CH:14][C:13]=1[C:28]([F:29])([F:30])[F:31]

Participants

4

Reactant 2

HCID 677755482-(4-(4-Chloro-3-(trifluoromethyl)phenoxy)phenyl)ethanamineHCID 178503551HCID 178503551, compound

Product 1

HCID 1784308912-{2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamino}-5-methyl-1H-pyrimidin-4-oneYield 35.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

5-Methyl-2-methylsulfanyl-1H-pyrimidin-4-one (25 mg, 0.16 mmol, 1 eq) and 2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamine (60 mg, 0.192 mmol, 1.2 eq) were stirred in 300 μl of absolute ethanol for 50 hours. Solvent was then evaporated and the resulting crude was purified by chromatography on BIOTAGE SP1 purification device using 11 g normal phase silica KP-NH column and DCM/MeOH solvent system (gradient 0-7% of MeOH in 20 column volumes). Solvent from the gathered fractions of appropriate composition was evaporated and the crude was triturated with cyclohexane to obtain 2-{2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamino}-5-methyl-1H-pyrimidin-4-one (24 mg, yield=33.9%, purity=96%) in form of white powder. MS: [M+H]+=424.31. 1H NMR (300 MHz; CDCl3) δ/ppm 1.79 (s, 3H), 2.90 (t, J=6.24 Hz, 2H), 3.52 (s, 2H), 3.56-3.67 (m, 2H), 6.23 (br.s., 1H), 6.92 (d, J=7.56 Hz, 2H), 7.00 (d, J=7.95 Hz, 1H), 7.21 (d, J=7.56 Hz, 2H), 7.28 (s, 1H) 7.38 (d, J=8.32 Hz, 1H), 7.63 (s, 1H), 11.62 (br.s., 1H).

Workup

  1. customSolvent was then evaporated
  2. customthe resulting crude was purified by chromatography on BIOTAGE SP1 purification device
  3. customSolvent from the gathered fractions of appropriate composition was evaporated
  4. customthe crude was triturated with cyclohexane

Sources & evidence

ORD record
ord-be184099834742dfa61f92e7104993ad
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Linked notes

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