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

HRID 2381768Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2381768
[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]

Komponenten

6

Edukt 3

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

Produkt 1

HCID 444673163-(4-(2-(4-(4-Acetylpiperazin-1-yl)phenylamino)-5-fluoropyrimidin-4-yl)piperazin-1-yl)-3-oxopropanenitrileAusbeute 63,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-828ed391280a4b72a3bea80f9e6d2afa
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08258144B2

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