Cesium carbonate → 7-(Cyclopropylamino)-5-(3,5-difluorophenylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde

HRID 624695Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 624695
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:9])[CH:8]=1)[NH2:5].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:17]1[CH:22]=[C:21]([N:23]([CH:31]2[CH2:33][CH2:32]2)C(=O)OC(C)(C)C)[N:20]2[N:34]=[CH:35][C:36]([CH:37]=[O:38])=[C:19]2[N:18]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOCC>[CH:31]1([NH:23][C:21]2[N:20]3[N:34]=[CH:35][C:36]([CH:37]=[O:38])=[C:19]3[N:18]=[C:17]([NH:5][C:4]3[CH:3]=[C:2]([F:1])[CH:8]=[C:7]([F:9])[CH:6]=3)[CH:22]=2)[CH2:32][CH2:33]1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 965953,5-DifluoroanilineHCID 634876Binap, (A+-)-HCID 58196421Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate

Produkt 1

HCID 583143057-(Cyclopropylamino)-5-(3,5-difluorophenylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehydeAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

3,5-Difluoroaniline (29 mg, 0.22 mmol), Cs2CO3 (67 mg, 0.21 mmol) were added to Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (50 mg, 0.15 mmol) dissolved in 1,4-dioxane (1 mL). Racemic BINAP (6 mg, 0.06 mmol) and palladium(II) acetate (4 mg, 0.04 mmol) were then added. The mixture was sealed and irradiated at 110° C. for 20 min in the microwave. Et2O (3 mL) was added and the solution was filtered. The filtrate was concentrated in vacuo. The crude residue was dissolved in dichloromethane (1.5 mL) and trifluoroacetic acid (1.5 mL). After 1 h, the solution was concentrated under a stream of air. The residue was triturated with 20% 2-propanol/hexanes. The product was filtered to yield 7-(cyclopropylamino)-5-(3,5-difluorophenylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde (39 mg, 80%). LCMS (M+1=330)

Aufarbeitung

  1. customThe mixture was sealed
  2. customirradiated at 110° C. for 20 min in the microwave
  3. filtrationthe solution was filtered
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutionThe crude residue was dissolved in dichloromethane (1.5 mL)
  6. concentrationthe solution was concentrated under a stream of air
  7. customThe residue was triturated with 20% 2-propanol/hexanes
  8. filtrationThe product was filtered

Quellen und Nachweise

ORD-Eintrag
ord-38813bad27a24948b4906a13d92a2a86
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303033B2

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