Sodium Carbonate → [5-[4-(4-Isopropyl-piperazin-1-ylmethyl)-phenyl]-6'-(1-methyl-1H-pyrazol-3-yl)-[3,4']bipyridinyl-2'-yl]-methyl-amine

To a solution of 4-(4-Isopropyl-piperazin-1-ylmethyl)-phenyl boronic acid (Intermediate B3) (1.5 eq, 0.218 mmol, 0.057 g) and 2M Na2CO3 (3.0 eq, 0.436 mmol, 0.218 ml) in DME (1 ml) is added [5-Bromo-6′-(1-methyl-1H-pyrazol-3-yl)-[3,4′]bipyridinyl-2′-yl]-methyl-amine (Example 2.178, step1) (1 eq, 0.145 mmol, 0.050 g) followed by [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.015 mmol, 0.012 g). The reaction mixture is heated using microwave radiation at 90° C. for 90 mins. The reaction mixture is dissolved in DCM and washed with water. The organic layer is washed with brine, dried over drying agent MgSO4, filtered and the organic solvent is reduced in vacuo. The crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-50% acetonitrile in water—0.1% TFA). The appropriate fractions by HPLC are combined and concentrated in vacuo. The resulting residue is dissolved in MeOH and loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 482.

1. temperatureThe reaction mixture is heated
2. customat 90° C.
3. customfor 90 mins
4. washwashed with water
5. washThe organic layer is washed with brine
6. customdried
7. dry with materialover drying agent MgSO4
8. filtrationfiltered
9. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-50% acetonitrile in water—0.1% TFA)
10. concentrationconcentrated in vacuo
11. dissolutionThe resulting residue is dissolved in MeOH
12. washeluting with MeOH
13. concentrationconcentrated in vacuo
14. customdried under vacuum

ORDレコード

ord-a9fd81fcc54f467eb5bafda1c4e1ebcf

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08343966B2