Sodium Carbonate → 2-((2R)-4-{2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methyl-4-pyrimidinyl}-2-methyl-1-piperazinyl)acetamide

HRID 1091957Notes

Reaction equation

HRID 1091957 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[N:14]=[C:13]([CH3:15])[C:12]([CH2:16][O:17][C:18]2[CH:23]=[C:22]([CH:24]([CH3:26])[CH3:25])[CH:21]=[CH:20][C:19]=2[CH3:27])=[C:11]([N:28]2[CH2:33][CH2:32][NH:31][C@H:30]([CH3:34])[CH2:29]2)[N:10]=1.Br[CH2:36][C:37]([NH2:39])=[O:38].C(=O)([O-])[O-].[Na+].[Na+]>CC(N(C)C)=O>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[N:10]=[C:11]([N:28]2[CH2:33][CH2:32][N:31]([CH2:36][C:37]([NH2:39])=[O:38])[C@H:30]([CH3:34])[CH2:29]2)[C:12]([CH2:16][O:17][C:18]2[CH:23]=[C:22]([CH:24]([CH3:26])[CH3:25])[CH:21]=[CH:20][C:19]=2[CH3:27])=[C:13]([CH3:15])[N:14]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 696322-BromoacetamideHCID 575314072-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methyl-6-[(3R)-3-methylpiperazin-1-yl]pyrimidine

Product 1

HCID 575313632-((2R)-4-{2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methyl-4-pyrimidinyl}-2-methyl-1-piperazinyl)acetamide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methyl-6-[(3R)-3-methylpiperazin-1-yl]pyrimidine (32 mg, 0.07 mmol), 2-bromoacetamide (29 mg, 0.21 mmol), sodium carbonate (44 mg) and DMA (1 mL) is heated at 60° C. under nitrogen with magnetic stirring for 18 h. The reaction mixture is allowed to cool and partitioned between EtOAc (8 mL) and water (2 mL). The organic layer is separated, washed with water (2 mL), 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, 5H), 6.81-6.83 (m, 2H), 5.58 (br d, J=6.3 Hz, 1H), 4.97 (dd, 2H), 3.77-3.86 (m, 2H), 3.25-3.33 (m, 2H), 2.80-3.00 (m, 4H), 2.45-2.62 (m, 5H), 2.22 (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 (8 mL) and water (2 mL)
  3. customThe organic layer is separated
  4. washwashed with water (2 mL), 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-6032acf791d04a76aed21e893e789356
Source dataset
uspto-grants-2012_03
Patent number
US08129395B2

Reaction notes

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