Potassium Carbonate → N2-(3-chloro-4-(4-methylpiperazin-1-yl)phenyl)-N4-cyclopropylfuro[3,2-d]pyrimidine-2,4-diamine

HRID 1038805

Reaktionsgleichung

Reaktionsgleichung von HRID 1038805
Cl[C:2]1[N:3]=[C:4]([NH:11][CH:12]2[CH2:14][CH2:13]2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=1[N:23]1[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]1)[NH2:19].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(O)(C)C>[Cl:15][C:16]1[CH:17]=[C:18]([NH:19][C:2]2[N:3]=[C:4]([NH:11][CH:12]3[CH2:14][CH2:13]3)[C:5]3[O:10][CH:9]=[CH:8][C:6]=3[N:7]=2)[CH:20]=[CH:21][C:22]=1[N:23]1[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]1

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 8203433-Chloro-4-(4-methylpiperazin-1-yl)anilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86665093HCID 86665093, Verbindung

Produkt 1

HCID 67129973N2-(3-chloro-4-(4-methylpiperazin-1-yl)phenyl)-N4-cyclopropylfuro[3,2-d]pyrimidine-2,4-diamineAusbeute 43,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a vial was added 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.099 g, 0.476 mmol, Preparation #A.1), 3-chloro-4-(4-methylpiperazin-1-yl)aniline (0.118 g, 0.523 mmol, Art-Chem), X-Phos (0.0136 g, 0.029 mmol), K2CO3 (0.079 g, 0.571 mmol), and Pd2dba3 (0.026 g, 0.029 mmol). t-BuOH (2 mL) was then added and tube was sealed. The tube was evacuated and purged with nitrogen (3×), and stirred overnight at about 85° C. The mixture was filtered, the filter pad was washed with EtOAc and then the solvent was removed in vacuo. The crude material was added to a silica gel column and was eluted with MeOH/DCM (2% to 10%). The sample was further purified by preparative reverse phase HPLC (Table 2, Method b). The collected fractions were dissolved in DCM (10 mL) and washed with saturated aqueous NaHCO3, (10 mL) and separated using a Biotage phase separator column. The filtrate was concentrated to provide N2-(3-chloro-4-(4-methylpiperazin-1-yl)phenyl)-N4-cyclopropylfuro[3,2-d]pyrimidine-2,4-diamine (0.082 g, 43%): LC/MS (Table 2, Method a) Rt=1.04 min; MS m/z 399.2 (M+H)+. Syk IC50=B

Aufarbeitung

  1. customtube was sealed
  2. customThe tube was evacuated
  3. custompurged with nitrogen (3×)
  4. filtrationThe mixture was filtered
  5. washthe filter pad was washed with EtOAc
  6. customthe solvent was removed in vacuo
  7. additionThe crude material was added to a silica gel column
  8. washwas eluted with MeOH/DCM (2% to 10%)
  9. customThe sample was further purified by preparative reverse phase HPLC (Table 2, Method b)
  10. dissolutionThe collected fractions were dissolved in DCM (10 mL)
  11. washwashed with saturated aqueous NaHCO3, (10 mL)
  12. customseparated
  13. concentrationThe filtrate was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-9c79c298687343adb4ccb9b914b32f9b
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551981B2

Verknüpfte Notizen

Wird geladen…