(1,1'-Biphenyl)-4-carboxylic acid → Biphenyl-4-yl-[3-(4-pyrimidin-2-yl-piperazin-1-yl)-azetidin-1-yl]-methanone
Reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]3[N:16]=[CH:15][CH:14]=[CH:13][N:12]=3)[CH2:7][CH2:6]2)[CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:50]1([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:55]=[CH:54][C:53]([C:56](O)=[O:57])=[CH:52][CH:51]=1>CN(C=O)C.O>[C:50]1([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH:51]=[CH:52][C:53]([C:56]([N:1]2[CH2:4][CH:3]([N:5]3[CH2:6][CH2:7][N:8]([C:11]4[N:12]=[CH:13][CH:14]=[CH:15][N:16]=4)[CH2:9][CH2:10]3)[CH2:2]2)=[O:57])=[CH:54][CH:55]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of 2-(4-azetidin-3-yl-piperazin-1-yl)-pyrimidine (0.172 g, 0.87 mmol) and HATU (0.347 g, 0.913 mmol) in DMF (4 mL) was added DIPEA (0.607 mL, 3.48 mmol). The mixture was stirred at room temperature for 30 min and then biphenyl-4-carboxylic acid (0.87 mmol) was added. The resulting mixture was stirred at room temperature for 5 h. H2O (8 mL) was added and the resulting mixture extracted with EtOAc (3×). The organic layer was dried over MgSO4 and concentrated. The resulting residue was purified by HPLC to yield biphenyl-4-yl-[3-(4-pyrimidin-2-yl-piperazin-1-yl)-azetidin-1-yl]-methanone.
Workup
- stirringThe resulting mixture was stirred at room temperature for 5 h
- extractionthe resulting mixture extracted with EtOAc (3×)
- dry with materialThe organic layer was dried over MgSO4
- concentrationconcentrated
- customThe resulting residue was purified by HPLC
Sources & evidence
- ORD record
- ord-be195aba47904282b04a210d41331b30
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08815839B2
Reaction notes
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