2-(4-(4-Chloro-3-(trifluoromethyl)phenoxy)phenyl)ethanamine → HCID 178516535, compound

HRID 705982Notes

Reaction equation

HRID 705982 reaction equation
CS[C:3]1[NH:4][CH:5]=[CH:6][C:7](=[O:9])[N:8]=1.[Cl:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][NH2:24])=[CH:18][CH:17]=2)=[CH:13][C:12]=1[C:27]([F:30])([F:29])[F:28]>N1C=CC=CC=1>[Cl:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][NH:24][C:3]3[NH:4][CH:5]=[CH:6][C:7](=[O:9])[N:8]=3)=[CH:18][CH:17]=2)=[CH:13][C:12]=1[C:27]([F:28])([F:29])[F:30]

Participants

4

Reactant 2

HCID 677755482-(4-(4-Chloro-3-(trifluoromethyl)phenoxy)phenyl)ethanamineHCID 178418670HCID 178418670, compound

Product 1

HCID 178516535HCID 178516535, compoundYield 77.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

2-Methylsulfanyl-1H-pyrimidin-4-one (70 mg, 0.492 mmol, 1.41 eq) and 2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamine (110 mg, 0.348 mmol, 1 eq) were heated in a sealed vial at 150° C. in 400 μl of dry pyridine for 16 hours. Solvent was then evaporated and the resulting crude was purified by chromatography on BIOTAGE SP1 purification device using 10 g normal phase silica SNAP column and DCM/30% MEOH in DCM solvent system (gradient 2-20% of 30% MeOH in DCM in 20 column volumes). Solvent from the gathered fractions of appropriate composition was evaporated and the resulting crude was triturated with diisopropyl ether and cyclohexane to afford 2-{2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamino}-1H-pyrimidin-4-one (111 mg, yield=73.8%, purity=95%) as a white powder. MS: [M+H]+=410.33 1H NMR (300 MHz; CDCl3) δ/ppm 2.92 (t, J=6.95 Hz, 2H), 3.61-3.72 (m, 2H), 5.59 (d, J=6.38 Hz, 1H), 6.18 (br.s, 1H), 6.95 (d, J=8.51 Hz, 2H), 7.03 (dd, J=9.07 Hz, J=2.69 Hz, 1H), 7.24 (d, J=8.51 Hz, 1H), 7.30 (d, J=2.69 Hz, 1H), 7.41 (d, J=8.80 Hz, 1H), 7.77 (d, J=6.38 Hz, 1H), 11.77 (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 resulting crude was triturated with diisopropyl ether and cyclohexane

Sources & evidence

ORD record
ord-6c98e9c7210443bbbae8a854d7218ff0
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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