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

HRID 706113Notes

Reaction equation

HRID 706113 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][NH2:15])=[CH:9][CH:8]=2)=[CH:4][C:3]=1[C:18]([F:21])([F:20])[F:19].CS[C:24]1[NH:25][CH:26]=[C:27]([CH2:31][C:32]2[CH:33]=[N:34][C:35](=[O:38])[NH:36][CH:37]=2)[C:28](=[O:30])[N:29]=1>N1C=CC=CC=1>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][NH:15][C:24]3[NH:25][CH:26]=[C:27]([CH2:31][C:32]4[CH:33]=[N:34][C:35](=[O:38])[NH:36][CH:37]=4)[C:28](=[O:30])[N:29]=3)=[CH:9][CH:8]=2)=[CH:4][C:3]=1[C:18]([F:19])([F:20])[F:21]

Participants

4

Reactant 2

HCID 677755482-(4-(4-Chloro-3-(trifluoromethyl)phenoxy)phenyl)ethanamineHCID 178503544HCID 178503544, compound

Product 1

HCID 1785177382-{2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]ethylamino}-5-(2-oxo-1,2-dihydro-pyrimidin-5-ylmethyl)-1H-pyrimidin-4-oneYield 17.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
150 °C

Procedure

2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamine (0.380 mmol, 1.00 eq) and 2-methylsulfanyl-5-(2-oxo-1,2-dihydro-pyrimidin-5-ylmethyl)-1H-pyrimidin-4-one (0.240 mmol, 0.63 eq) were dissolved in dry pyridine (300 μL) and stirred at 150° C. overnight. Solvent was evaporated and crude product was purified on Biotage SP1 Snap Si 10; 15 ml/min in the gradient of MeOH in DCM: 0-10% in 25CV. The appropriate fractions were combined and evaporated in vacuo to give the required product 2-{2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]ethylamino}-5-(2-oxo-1,2-dihydro-pyrimidin-5-ylmethyl)-1H-pyrimidin-4-one (0.041 mmol, yield: 11%, HPLC-MS/UV:[M+H]+=518.047; rt: 10.97 mins; purity: 85%). 1H NMR (300 MHz; CDCl3) δ/ppm 2.80 (t, J=6.50, 2H), 3.19-3.22 (m, 2H), 3.41-3.52 (m, 2H), 5.39 (br.s., 1H), 6.33-6.64 (m, 1H), 6.99-7.10 (m, 2H), 7.22 (dd, J=9.24, J=3.42, 1H), 7.26-7.32 (m, 2H), 7.38-7.43 (m, 1H), 7.58-7.72 (m, 2H), 8.11 (br.s., 1H), 10.93 (br.s., 1H)

Workup

  1. customSolvent was evaporated
  2. customcrude product was purified on Biotage SP1 Snap Si 10
  3. customevaporated in vacuo

Sources & evidence

ORD record
ord-52b1d4bb05c541ba97e5de885fce2b76
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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