Cyanoacetic acid → 3-(4-(2-(4-(4-Acetylpiperazin-1-yl)phenylamino)-5-fluoropyrimidin-4-yl)piperazin-1-yl)-3-oxopropanenitrile

HRID 2281542Notes

Reaction equation

HRID 2281542 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[F:13][C:14]1[C:15]([N:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)=[N:16][C:17]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:33](=[O:35])[CH3:34])[CH2:29][CH2:28]3)=[CH:23][CH:22]=2)=[N:18][CH:19]=1>C(Cl)Cl.CN(C=O)C>[C:33]([N:30]1[CH2:31][CH2:32][N:27]([C:24]2[CH:25]=[CH:26][C:21]([NH:20][C:17]3[N:16]=[C:15]([N:36]4[CH2:37][CH2:38][N:39]([C:4](=[O:6])[CH2:3][C:1]#[N:2])[CH2:40][CH2:41]4)[C:14]([F:13])=[CH:19][N:18]=3)=[CH:22][CH:23]=2)[CH2:28][CH2:29]1)(=[O:35])[CH3:34]

Participants

6

Reactant 3

HCID 9740Cyanoacetic acidHCID 65578Oxalyl chlorideHCID 444671001-(4-(4-(5-Fluoro-4-(piperazin-1-yl)pyrimidin-2-ylamino)phenyl)piperazin-1-yl)ethanone

Product 1

HCID 444673163-(4-(2-(4-(4-Acetylpiperazin-1-yl)phenylamino)-5-fluoropyrimidin-4-yl)piperazin-1-yl)-3-oxopropanenitrileYield 63.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneCatalystHCID 6228DimethylformamideSolvent

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 50 min. To the above solution cooled in an ice bath, a solution of 1-(4-(4-(5-fluoro-4-(piperazin-1-yl)pyrimidin-2-ylamino)phenyl)piperazin-1-yl)ethanone (23 mg, 0.057 mmol) and TEA (0.400 mL, 2.87 mmol) in DMF (1 mL) was added drop wise. The mixture was then stirred at room temperature for 90 min. It was concentrated in vacuo. The residue was purified by HPLC to give the titled compound (17 mg). MS 467.5 (M+H); UV 201.0, 269.4 nm

Workup

  1. temperatureTo the above solution cooled in an ice bath
  2. stirringThe mixture was then stirred at room temperature for 90 min
  3. concentrationIt was concentrated in vacuo
  4. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-e70ba57cd58a45f6bf73c387f50a8139
Source dataset
uspto-grants-2015_09
Patent number
US09139581B2

Reaction notes

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