2-[4-(3-Trifluoromethyl-phenoxy)-phenyl]-ethylamine → HCID 178518122, compound

HRID 474867Notes

Reaction equation

HRID 474867 reaction equation
CS[C:3]1[NH:4][CH:5]=[C:6]([CH2:10][C:11]2[CH:12]=[N:13][CH:14]=[N:15][CH:16]=2)[C:7](=[O:9])[N:8]=1.[F:17][C:18]([F:36])([F:35])[C:19]1[CH:20]=[C:21]([CH:32]=[CH:33][CH:34]=1)[O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][NH2:31])=[CH:25][CH:24]=1>C(O)C>[N:13]1[CH:12]=[C:11]([CH2:10][C:6]2[C:7](=[O:9])[N:8]=[C:3]([NH:31][CH2:30][CH2:29][C:26]3[CH:25]=[CH:24][C:23]([O:22][C:21]4[CH:32]=[CH:33][CH:34]=[C:19]([C:18]([F:17])([F:35])[F:36])[CH:20]=4)=[CH:28][CH:27]=3)[NH:4][CH:5]=2)[CH:16]=[N:15][CH:14]=1

Participants

4

Reactant 2

HCID 677762212-[4-(3-Trifluoromethyl-phenoxy)-phenyl]-ethylamineHCID 178503543HCID 178503543, compound

Product 1

HCID 178518122HCID 178518122, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

2-Methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one (40 mg, 0.171 mmol, 1 eq) and 2-[4-(3-trifluoromethyl-phenoxy)-phenyl]-ethylamine (53 mg, 0.188 mmol, 1.1 eq) were dissolved in dry ethanol (300 μl) and stirred at 120° C. for 6 h. Ethanol was evaporated during the reaction and in the mixture was added pyridine (300 μl) and reaction was stirred for 3 h. Pyridine was evaporated and 0.5 ml of EtOH was added. Precipitate was formed and it was starting material. Mother liquor was evaporated and purified via Biotage SP-1 Snap Si 10 g in the gradient of MeOH in DCM: 1% for 1 CV, 1-5% for 18 CV; 5-10% for 20 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product which was not pure enough and it was sent to HPLC/MS Purification. After HPLC/MS purification combined fractions of desired product were collected and put on lyophilisation to obtain 5-pyrimidin-5-ylmethyl-2-{2-[4-(3-trifluoromethyl-phenoxy)-phenyl]-ethylamino}-1H-pyrimidin-4-one (0.0087 mmol; yield: 5.1%, HPLC-MS/UV: [M+H]+=468.45; rt: 10.90 min; purity: 94.9%). 1H NMR (300 MHz; DMSO-d6) δ/ppm 2.78 (t, J=7.17 Hz, 2H), 3.41-3.47 (m, 2H), 3.50 (s, 2H), 6.99 (d, J=8.40 Hz, 2H), 7.22 (d, J=8.34 Hz, 1H), 7.24-7.31 (m, 3H), 7.44 (d, J=7.82 Hz, 1H), 7.56 (s, J=7.92 Hz, 1H), 7.60 (s, 1H), 8.66 (s, 2H), 8.94 (s, 1H)

Workup

  1. customEthanol was evaporated during the reaction and in the mixture
  2. additionwas added
  3. custompyridine (300 μl) and reaction
  4. stirringwas stirred for 3 h
  5. customPyridine was evaporated
  6. addition0.5 ml of EtOH was added
  7. customPrecipitate was formed
  8. customMother liquor was evaporated
  9. custompurified via Biotage SP-1 Snap Si 10 g in the gradient of MeOH in DCM
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-172c3038d4e34ea492bd2dd14206a537
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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