N-methyl-2-pyrrolidone → 2-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-amide
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[NH2:23][N:24]1[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][OH:32])[CH2:26][CH2:25]1.CN1C(=O)CCC1>C(Cl)Cl.CN(C=O)C>[OH:32][CH2:31][CH2:30][N:27]1[CH2:28][CH2:29][N:24]([NH:23][C:14]([C:11]2[CH:12]=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)=[O:16])[CH2:25][CH2:26]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (0.28 g, 1.4 mmol) in anhydrous DCM (10 mL) at 0° C. is added the oxalyl chloride (0.18 mL, 1.4 mmol) followed by the addition of DMF (0.11 mL). The mixture is stirred at 0° C. for 30 min, and then allowed to warm up to rt and stirred for 30 min. The mixture is concentrated in vacuo. The residue is dissolved in anhydrous DCM (10 mL). 2-(4-Amino-piperazin-1-yl)-ethanol (0.145 g, 1 mmol) is added at rt followed by the addition of NMP (0.19 mL, 2 mmol). The mixture is stirred at rt for 2 h and the mixture is then concentrated in vacuo. The residue is triturated in Et2O and the resulting solid is collected by filtration to afford 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-amide (0.16 g). MS: 346 (M+H).
Workup
- temperatureto warm up to rt
- stirringstirred for 30 min
- concentrationThe mixture is concentrated in vacuo
- dissolutionThe residue is dissolved in anhydrous DCM (10 mL)
- stirringThe mixture is stirred at rt for 2 h
- concentrationthe mixture is then concentrated in vacuo
- customThe residue is triturated in Et2O
- filtrationthe resulting solid is collected by filtration
Sources & evidence
- ORD record
- ord-0be5f208e3ac46e68b36ea5b3e811615
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258130B2
Reaction notes
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