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

HRID 1798485노트

반응식

HRID 1798485 반응식
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[C:11](B(O)O)[CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[Na+].[Na+].Br[C:25]1[CH:26]=[C:27]([C:31]2[CH:36]=[C:35]([NH:37][CH3:38])[N:34]=[C:33]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=3)[CH:32]=2)[CH:28]=[N:29][CH:30]=1.C(Cl)Cl>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:38][NH:37][C:35]1[N:34]=[C:33]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=2)[CH:32]=[C:31]([C:27]2[CH:28]=[N:29][CH:30]=[C:25]([C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([CH2:8][N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)[CH:10]=3)[CH:26]=2)[CH:36]=1

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 496578973-((4-Methylpiperazin-1-yl)methyl)phenylboronic acid2회HCID 86633643(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-methyl-amine

생성물 1

HCID 68759494Methyl-{5''-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[2,2';4',3'']terpyridin-6'-yl}-amine

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 3-((4-Methyl-piperazin-1-yl)methyl)-phenyl boronic acid (Intermediate B1) (1.2 eq, 0.704 mmol, 0.165 g) and 2M Na2CO3 (2.0 eq, 1.17 mmol, 0.6 ml) in DME (3 ml) is added (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-methyl-amine (Example 2.1; step1) (1 eq, 0.586 mmol, 0.2 g) followed by [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.058 mmol, 0.043 g). The reaction mixture is heated using microwave radiation at 90° C. for 4 hours. 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, 0-20% 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 2 M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 451.

후처리

  1. temperatureThe reaction mixture is heated
  2. customat 90° C.
  3. customfor 4 hours
  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, 0-20% 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

출처 및 근거

ORD 기록
ord-400a869548814c7d83e74d652e98a11e
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08343966B2

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