Diisopropylethylamine → 2-[4-(1-Benzhydryl-azetidin-3-yl)-piperazin-1-yl]-pyrimidine

HRID 2408270Notes

Reaction equation

HRID 2408270 reaction equation
[N:1]1([C:7]2[N:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH:13]([N:26]1[CH2:29][CH:28](OS(C)(=O)=O)[CH2:27]1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCN(C(C)C)C(C)C>CC#N>[CH:13]([N:26]1[CH2:29][CH:28]([N:4]2[CH2:5][CH2:6][N:1]([C:7]3[N:8]=[CH:9][CH:10]=[CH:11][N:12]=3)[CH2:2][CH2:3]2)[CH2:27]1)([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 887471-(2-Pyrimidinyl)piperazineHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonate

Product 1

HCID 667704982-[4-(1-Benzhydryl-azetidin-3-yl)-piperazin-1-yl]-pyrimidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-piperazin-1-yl-pyrimidine (2.48 g, 15.10 mmol, Alfa) and methanesulfonic acid 1-benzhydryl-azetidin-3-yl ester (4 g, 12.6 mmol, Oakwood) in CH3CN (40 mL) was added DIPEA (2.63 mL, 15.10 mmol) at room temperature. The resulting mixture was then refluxed for 2 h. The solvent was removed by evaporation and the residue was partitioned between CH2Cl2 and aqueous NaHCO3. The organic layer was washed with aqueous NaHCO3 (2×) and then extracted with 1N HCl (2×). The aqueous layer was cooled and then pH adjusted with 1N NaOH. The resulting mixture was extracted with CH2Cl2 (2×). The organic layer was dried over MgSO4 and concentrated. The resulting residue was purified by MPLC to yield 2-[4-(1-benzhydryl-azetidin-3-yl)-piperazin-1-yl]-pyrimidine.

Workup

  1. temperatureThe resulting mixture was then refluxed for 2 h
  2. customThe solvent was removed by evaporation
  3. customthe residue was partitioned between CH2Cl2 and aqueous NaHCO3
  4. washThe organic layer was washed with aqueous NaHCO3 (2×)
  5. extractionextracted with 1N HCl (2×)
  6. temperatureThe aqueous layer was cooled
  7. extractionThe resulting mixture was extracted with CH2Cl2 (2×)
  8. dry with materialThe organic layer was dried over MgSO4
  9. concentrationconcentrated
  10. customThe resulting residue was purified by MPLC

Sources & evidence

ORD record
ord-7a68c72f42c64ad0816b486be8a0477a
Source dataset
uspto-grants-2014_08
Patent number
US08815839B2

Reaction notes

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