Sodium Carbonate → 2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methyl-6-[(3R)-3-methylpiperazin-1-yl]pyrimidine

HRID 1091956Notes

Reaction equation

HRID 1091956 reaction equation
Cl[C:2]1[C:7]([CH2:8][O:9][C:10]2[CH:15]=[C:14]([CH:16]([CH3:18])[CH3:17])[CH:13]=[CH:12][C:11]=2[CH3:19])=[C:6]([CH3:20])[N:5]=[C:4]([C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:28])[N:3]=1.[CH3:29][C@@H:30]1[CH2:35][NH:34][CH2:33][CH2:32][NH:31]1.C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:28][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]([CH3:27])[C:21]=1[C:4]1[N:5]=[C:6]([CH3:20])[C:7]([CH2:8][O:9][C:10]2[CH:15]=[C:14]([CH:16]([CH3:18])[CH3:17])[CH:13]=[CH:12][C:11]=2[CH3:19])=[C:2]([N:34]2[CH2:33][CH2:32][NH:31][C@H:30]([CH3:29])[CH2:35]2)[N:3]=1

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 73304342-Methylpiperazine, (R)-HCID 575314014-Chloro-2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidine

Product 1

HCID 575314072-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methyl-6-[(3R)-3-methylpiperazin-1-yl]pyrimidine

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidine (0.1 mmol in 0.5 mL DMA), (R)-2-methyl-piperazine (40 mg) and sodium carbonate (85 mg) is heated at 100° C. with agitation for 18 h. The reaction mixture is allowed to cool and partitioned between EtOAc (6 mL) and water (2 mL). The organic layer is separated, washed with water (2 mL×2), brine (2 mL), dried over anhydrous sodium sulfate, filtered and evaporated to obtain a colorless oil. Purification by chromatography on silica gel (2% MeOH/DCM/0.1% Ammonium hydroxide) provides the title compound as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.06-7.26 (m, 4H), 6.79-6.82 (m, 2H), 4.97 (dd, 2H), 3.89-3.96 (m, 2H), 2.87-3.05 (m, 5H), 2.62-2.69 (m, 1H), 2.56 (s, 3H), 2.23 (s, 3H), 2.16 (s, 6H), 1.27 (d, J=6.8 Hz, 6H), 0.93 (d, J=6.6 Hz, 3H).

Workup

  1. temperatureto cool
  2. custompartitioned between EtOAc (6 mL) and water (2 mL)
  3. customThe organic layer is separated
  4. washwashed with water (2 mL×2), brine (2 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto obtain a colorless oil
  9. customPurification by chromatography on silica gel (2% MeOH/DCM/0.1% Ammonium hydroxide)

Sources & evidence

ORD record
ord-ac8a46050d424f4e9f2e7e37cd822d5a
Source dataset
uspto-grants-2012_03
Patent number
US08129395B2

Reaction notes

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