Cyanoacetic acid → N-(1-(2-(4-(4-acetylpiperazin-1-yl)phenylamino)-5-fluoropyrimidin-4-yl)piperidin-4-yl)-2-cyanoacetamide
Reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]2[C:25]([F:26])=[CH:24][N:23]=[C:22]([NH:27][C:28]3[CH:33]=[CH:32][C:31]([N:34]4[CH2:39][CH2:38][N:37]([C:40](=[O:42])[CH3:41])[CH2:36][CH2:35]4)=[CH:30][CH:29]=3)[N:21]=2)[CH2:16][CH2:15]1>C(Cl)Cl.CN(C=O)C>[C:40]([N:37]1[CH2:38][CH2:39][N:34]([C:31]2[CH:32]=[CH:33][C:28]([NH:27][C:22]3[N:21]=[C:20]([N:17]4[CH2:16][CH2:15][CH:14]([NH:13][C:4](=[O:6])[CH2:3][C:1]#[N:2])[CH2:19][CH2:18]4)[C:25]([F:26])=[CH:24][N:23]=3)=[CH:29][CH:30]=2)[CH2:35][CH2:36]1)(=[O:42])[CH3:41]Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a suspension of cyanoacetic acid (85 mg, 1.00 mmol) in CH2Cl2 (2 mL) (containing 2 drops of DMF) at room temperature, oxalyl chloride (0.082 mL, 0.94 mmol) was added. Gas evolved and suspension became clear. It was then stirred for 30 min. To the above solution cooled in an ice bath, a solution of 1-(4-(4-(4-(4-aminopiperidin-1-yl)-5-fluoropyrimidin-2-ylamino)phenyl)piperazin-1-yl)ethanone (70 mg, 0.17 mmol) and TEA (0.478 mL, 3.43 mmol) in DMF (2 mL) was added drop wise. The mixture was then stirred at room temperature for 3 h. It was concentrated in vacuo. The residue was purified by HPLC to give the titled compound (12 mg). MS 481.5 (M+H); UV 204.7, 266.3 nm
Workup
- temperatureTo the above solution cooled in an ice bath
- stirringThe mixture was then stirred at room temperature for 3 h
- concentrationIt was concentrated in vacuo
- customThe residue was purified by HPLC
Sources & evidence
- ORD record
- ord-3da3550167af43cb945697755561bcc2
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139581B2
Reaction notes
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