Dimethylformamide → 2-Chloro-4-[4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]pyrimidine

HRID 2063894Notes

Reaction equation

HRID 2063894 reaction equation
CN(C=O)C.[CH3:6][C:7]1([CH3:25])[CH2:11][C:10]2[C:12]([CH3:24])=[C:13]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[C:14]([CH3:17])=[C:15]([CH3:16])[C:9]=2[O:8]1.[Cl:26][C:27]1[N:32]=[C:31]([Cl:33])[CH:30]=[CH:29][N:28]=1.C(N(CC)CC)C>O>[Cl:26][C:27]1[N:32]=[C:31]([N:21]2[CH2:20][CH2:19][N:18]([C:13]3[C:14]([CH3:17])=[C:15]([CH3:16])[C:9]4[O:8][C:7]([CH3:25])([CH3:6])[CH2:11][C:10]=4[C:12]=3[CH3:24])[CH2:23][CH2:22]2)[CH:30]=[CH:29][N:28]=1.[Cl:33][C:31]1[CH:30]=[CH:29][N:28]=[C:27]([N:21]2[CH2:20][CH2:19][N:18]([C:13]3[C:14]([CH3:17])=[C:15]([CH3:16])[C:9]4[O:8][C:7]([CH3:25])([CH3:6])[CH2:11][C:10]=4[C:12]=3[CH3:24])[CH2:23][CH2:22]2)[N:32]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 775312,4-DichloropyrimidineHCID 667597311-(2,2,4,6,7-Pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazine

Product 2

HCID 594850032-Chloro-4-[4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]pyrimidineYield 62%HCID 594851154-Chloro-2-[4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]pyrimidineYield 4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To the DMF (10 mL) solution of 1-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazine (1.92 g, 7.00 mmol) synthesized in Reference example 61, 2,4-dichloropyrimidine (1.04 g, 7.00 mmol) and triethylamine (1.07 mL, 7.70 mmol) were added and the mixture was stirred at room temperature for 1 hour. To the mixture solution, water was added. The extraction was carried out by using ethyl acetate, and the extract was dried over anhydrous magnesium sulfate. Then, the solvent was removed by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate 95:5-85:15) to obtain 2-chloro-4-[4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]pyrimidine 1.68 g (ethyl acetate/hexane=4:1, Rf=0.1, yield 62%) and 4-chloro-2-[4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazin-1-yl]pyrimidine 100 mg (ethyl acetate/hexane=4:1, Rf=0.5, yield 4%).

Workup

  1. additionwere added
  2. extractionThe extraction
  3. dry with materialthe extract was dried over anhydrous magnesium sulfate
  4. customThen, the solvent was removed by distillation under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate 95:5-85:15)

Sources & evidence

ORD record
ord-7c42e55cf1d14039ae90725260a79b90
Source dataset
uspto-grants-2012_10
Patent number
US08288390B2

Reaction notes

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