Reaktion #1125987

Reaktionsgleichung

2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine

3-chloro-4-(4-methylpiperazin-1-yl)aniline

X-Phos

K2CO3

→

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

Ausbeute 43.2%

Lösungsmittel

t-BuOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigetube was sealed
2. 2
   SonstigeThe tube was evacuated
3. 3
   Sonstigepurged with nitrogen (3×)
4. 4
   FiltrationThe mixture was filtered
5. 5
   Waschenthe filter pad was washed with EtOAc
6. 6
   Sonstigethe solvent was removed in vacuo
7. 7
   workup.ADDITIONThe crude material was added to a silica gel column
8. 8
   Waschenwas eluted with MeOH/DCM (2% to 10%)
9. 9
   SonstigeThe sample was further purified by preparative reverse phase HPLC (Table 2, Method b)
10. 10
    workup.DISSOLUTIONThe collected fractions were dissolved in DCM (10 mL)
11. 11
    Waschenwashed with saturated aqueous NaHCO3, (10 mL)
12. 12
    Sonstigeseparated
13. 13
    EinengenThe filtrate was concentrated

Vorschrift

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

Quelle