Dicyclohexylcarbodiimide → HCID 178480883, Verbindung

HRID 624804Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 624804
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:32])=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][CH:16]3[CH2:18][CH2:17]3)[N:12]3[N:19]=[CH:20][C:21](/[CH:22]=[C:23]4/[C:24](=[O:31])[N:25]([CH2:29][OH:30])[C:26](=[O:28])[NH:27]/4)=[C:11]3[N:10]=2)[CH:7]=1.[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][C:42](O)=[O:43])[CH2:36][CH2:35]1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][C:42]([O:30][CH2:29][N:25]2[C:24](=[O:31])/[C:23](=[CH:22]/[C:21]3[CH:20]=[N:19][N:12]4[C:13]([NH:15][CH:16]5[CH2:17][CH2:18]5)=[CH:14][C:9]([NH:8][C:6]5[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=5[F:32])=[N:10][C:11]=34)/[NH:27][C:26]2=[O:28])=[O:43])[CH2:36][CH2:35]1

Komponenten

7

Edukt 3

HCID 10868DicyclohexylcarbodiimideHCID 13953803-(4-Methylpiperazin-1-yl)propanoic acidHCID 178517689HCID 178517689, Verbindung

Produkt 1

HCID 178480883HCID 178480883, VerbindungAusbeute 26,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To (Z)-5-((5-(5-chloro-2-fluorophenylamino)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)-3-(hydroxymethyl)imidazolidine-2,4-dione (100 mg, 0.218 mmol) in DMF (3 mL) was added 3-(4-methylpiperazin-1-yl)propanoic acid (75 mg, 0.436 mmol), dicyclohexylcarbodiimide (90 mg, 0.436 mmol), and DMAP (4.0 mg, 0.33 mmol). The reaction mixture was stirred at room temperature overnight and then diluted with ethyl acetate and washed 1× water, 3× brine. The organic layer was dried with MgSO4, filtered and adsorbed onto silica gel. The crude material was purified by column chromatography eluting with 0-10% MeOH/CH2Cl2 gradient. Pure fractions were combined and the solvent was removed. This material was crystallized from ethyl acetate and hexane to provide 35 mg (26%) of (Z)-(4-((5-(5-chloro-2-fluorophenylamino)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)-2,5-dioxoimidazolidin-1-yl)methyl 3-(4-methylpiperazin-1-yl)propanoate as a yellow solid. LCMS (ES): >95% pure, m/z 612 [M+1]+.

Aufarbeitung

  1. washwashed 1× water, 3× brine
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. customThe crude material was purified by column chromatography
  5. washeluting with 0-10% MeOH/CH2Cl2 gradient
  6. customthe solvent was removed
  7. customThis material was crystallized from ethyl acetate and hexane

Quellen und Nachweise

ORD-Eintrag
ord-d164bf10730342b988c9adbe5762e274
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303033B2

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