2-Methylsulfonyl-4-benzyloxy-pyrimidine → 4-{4-[3-(4-Benzyloxy-pyrimidin-2-yloxy)-propyl]-piperazin-1-yl}-2-tert-butyl-6-cyclobutyl-pyrimidine

HRID 219736Notes

Reaction equation

HRID 219736 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][OH:20])[CH2:13][CH2:12]2)[CH:8]=[C:7]([CH:21]2[CH2:24][CH2:23][CH2:22]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[CH2:30]([O:37][C:38]1[CH:43]=[CH:42][N:41]=[C:40](S(C)(=O)=O)[N:39]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O1CCCC1>[CH2:30]([O:37][C:38]1[CH:43]=[CH:42][N:41]=[C:40]([O:20][CH2:19][CH2:18][CH2:17][N:14]2[CH2:13][CH2:12][N:11]([C:9]3[CH:8]=[C:7]([CH:21]4[CH2:24][CH2:23][CH2:22]4)[N:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[N:10]=3)[CH2:16][CH2:15]2)[N:39]=1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 113575332-Methylsulfonyl-4-benzyloxy-pyrimidineHCID 690262333-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-olHCID 178418339Butyllithium

Product 1

HCID 690276004-{4-[3-(4-Benzyloxy-pyrimidin-2-yloxy)-propyl]-piperazin-1-yl}-2-tert-butyl-6-cyclobutyl-pyrimidineYield 53.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

0.9 g of 3-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-ol (2.71 mmol) were dissolved in 20 ml of tetrahydrofuran. 2.75 ml of n-butyllithium (15% in hexane) were added at 0° C. The reaction mixture was stirred for 30 min. 0.79 g of 4-benzyloxy-2-methanesulfonyl-pyrimidine (3.0 mmol) dissolved in 10 ml of tetrahydrofuran were then added. The reaction mixture was stirred overnight at room temperature and for an additional 6 h at 60° C. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and the solvent was evaporated. The crude product was purified by chromatography on silica gel using dichloromethane-methanol (1.5%) as eluent to yield 0.75 g of the title compound.

Workup

  1. additionwere then added
  2. stirringThe reaction mixture was stirred overnight at room temperature and for an additional 6 h at 60° C
  3. customThe reaction mixture was partitioned between water and ethyl acetate
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe crude product was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-963166b782764b7a8233dbb6ed80b0fa
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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