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

HRID 219743Notes

Reaction equation

HRID 219743 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[CH2:23][CH2:22]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[CH2:29]([O:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39](S(C)(=O)=O)[N:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O1CCCC1>[CH2:29]([O:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]([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[CH2:23][CH2:22]4)[N:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[N:10]=3)[CH2:16][CH2:15]2)[N:38]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

5

Reactant 3

HCID 113575332-Methylsulfonyl-4-benzyloxy-pyrimidineHCID 690296093-[4-(2-tert-Butyl-6-cyclopropyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-olHCID 178418339Butyllithium

Product 1

HCID 690272064-{4-[3-(4-Benzyloxy-pyrimidin-2-yloxy)-propyl]-piperazin-1-yl}-2-tert-butyl-6-cyclopropyl-pyrimidineYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

0.5 g of 3-[4-(2-tert-Butyl-6-cyclopropyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-ol (1.57 mmol) were dissolved in 5 ml of tetrahydrofuran. 1.5 ml of n-butyllithium (15% in hexane) were added to the mixture at 0° C. Stirring was continued for 30 min and then 0.45 g of 4-benzyloxy-2-methanesulfonyl-pyrimidine (1.7 mmol) dissolved in 5 ml of tetrahydrofuran were added. The reaction was stirred overnight at room temperature and for an additional 2 h at 40° 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 (0-3%) as eluent to yield 0.6 g of the title compound.

Workup

  1. additionwere added
  2. stirringThe reaction was stirred overnight at room temperature and for an additional 2 h at 40° 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-f94a99ec79cf4c3f8e1195824168c5cf
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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