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

HRID 2036924Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2036924
[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)OCCCC)[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 86762115Butyl 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 Ten-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-017c4427606840979d9adfdfb51782fb
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08575177B2

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