Dichloromethane → Cyclopropyl-{6-methyl-5''-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[2,2';4',3'']terpyridin-6'-yl}-amine

To a solution of 3-((4-Methyl-piperazin-1-yl)methyl)-phenyl boronic acid (Intermediate B1) (1.2 eq, 0.157 mmol, 0.037 g) and 2M Na2CO3 (2.0 eq, 0.262 mmol, 0.1 ml) in DME (1 ml) is added (5″-Bromo-6-methyl-[2,2′;4′,3″]terpyridin-6′-yl)-cyclopropyl-amine (Example 2.36; step1) (1 eq, 0.131 mmol, 0.05 g) followed by [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.013 mmol, 9.6 mg). The reaction mixture is heated using microwave radiation at 90° C. for 1 hour 30 mins. The reaction mixture is dissolved in EtOAc 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, 0-30% 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]+ 491.

1. temperatureThe reaction mixture is heated
2. customat 90° C.
3. customfor 1 hour
4. custom30 mins
5. washwashed with water
6. washThe organic layer is washed with brine
7. customdried
8. dry with materialover drying agent MgSO4
9. filtrationfiltered
10. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-30% acetonitrile in water—0.1% TFA)
11. concentrationconcentrated in vacuo
12. dissolutionThe resulting residue is dissolved in MeOH
13. washeluting with MeOH
14. concentrationconcentrated in vacuo
15. customdried under vacuum

ORDレコード

ord-d5b9478405ca431697583c6180a856e6

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08343966B2