HCID 67774711, compound → 2-({2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-methyl-amino)-1-methyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one

HRID 474877Notes

Reaction equation

HRID 474877 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6]([CH2:8][C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)[C:5](=[O:15])[N:4]=[C:3]1SC.[Cl:18][C:19]1[CH:35]=[CH:34][C:22]([O:23][C:24]2[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][NH:32][CH3:33])=[CH:26][CH:25]=2)=[CH:21][C:20]=1[C:36]([F:39])([F:38])[F:37]>C(O)C>[Cl:18][C:19]1[CH:35]=[CH:34][C:22]([O:23][C:24]2[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][N:32]([CH3:33])[C:3]3[N:2]([CH3:1])[CH:7]=[C:6]([CH2:8][C:9]4[CH:10]=[N:11][CH:12]=[N:13][CH:14]=4)[C:5](=[O:15])[N:4]=3)=[CH:26][CH:25]=2)=[CH:21][C:20]=1[C:36]([F:37])([F:38])[F:39]

Participants

4

Reactant 2

HCID 67774711HCID 67774711, compoundHCID 677748841-methyl-2-methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one

Product 1

HCID 677746992-({2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-methyl-amino)-1-methyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-oneYield 28.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
130 °C

Procedure

1-Methyl-2-methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one (50 mg, 0.201 mmol, 1 eq) and {2-[4-(4-Chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-methyl-amine (99.4 mg, 0.302 mmol, 1.5 eq) were dissolved in dry ethanol (300 μl) and stirred at 130° C. for 48 h. Reaction mixture was evaporated and crude residue was purified via Biotage SP-1 Snap Si 10 g; 15 ml/min; UV Wavelength (Collection: 254 nm; Monitor: 290 nm) in the gradient of MeOH in DCM: 0% for 1 CV, 0-8% for 25 CV. The appropriate fractions were combined and product 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 2-({2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-methyl-amino)-1-methyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one (0.058 mmol; yield: 28.9%, HPLC-MS/UV: [M+H]+=530.95; rt: 12.13 min; purity: 99%). 1H NMR (300 MHz; DMSO-d6) δ/ppm 1.38 (s, 3H), 2.81 (s, 3H), 2.87 (t, J=6.73 Hz, 2H), 3.38 (t, J=7.20 Hz, 2H), 3.50 (s, 2H), 7.02 (d, J=7.20, 2H), 7.18 (d, J=8.17, 1H), 7.31 (d, J=8.17, 2H), 7.37 (s, 1H), 7.50 (s, 1H), 7.67 (d, J=8.65, 1H), 8.67 (s, 2H), 8.97 (s, 1H)

Workup

  1. customReaction mixture
  2. customwas evaporated
  3. customcrude residue was purified via Biotage SP-1 Snap Si 10 g
  4. customUV Wavelength (Collection: 254 nm; Monitor: 290 nm) in the gradient of MeOH in DCM
  5. customit was sent to HPLC/MS Purification
  6. customAfter HPLC/MS purification
  7. customwere collected

Sources & evidence

ORD record
ord-72c3f8ed4b8f44ad85e8045dd0f11168
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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