Sodium Carbonate → [5''-(3-Aminomethyl-5-methyl-phenyl)-[2,2';4',3'']terpyridin-6'-yl]-ethyl-amine

HRID 1798509노트

반응식

HRID 1798509 반응식
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[C:7]([CH3:9])[CH:8]=1.C([O-])([O-])=O.[Na+].[Na+].Br[C:20]1[CH:21]=[C:22]([C:26]2[CH:31]=[C:30]([NH:32][CH2:33][CH3:34])[N:29]=[C:28]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)[CH:27]=2)[CH:23]=[N:24][CH:25]=1>COCCOC.C(Cl)Cl.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]>[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[CH:21]=[C:22]([C:26]3[CH:31]=[C:30]([NH:32][CH2:33][CH3:34])[N:29]=[C:28]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=4)[CH:27]=3)[CH:23]=[N:24][CH:25]=2)[CH:6]=[C:7]([CH3:9])[CH:8]=1

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 44135952(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-ethylamineHCID 866336493-Aminomethyl-5-methyl-phenyl boronic acid

생성물 1

HCID 86633648[5''-(3-Aminomethyl-5-methyl-phenyl)-[2,2';4',3'']terpyridin-6'-yl]-ethyl-amine

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6344Dichloromethane용매2회HCID 80711,2-Dimethoxyethane용매

실험 절차

To a solution of 5″-(3-Aminomethyl-5-methyl-phenyl boronic acid (Intermediate B27) (2.0 eq, 0.303 mmol, 50 mg) and 2M Na2CO3 (2.0 eq, 0.303 mmol, 0.152 ml) in DME (1 ml) is added (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-ethylamine (Ex. 1.24) (1 eq, 0.152 mmol, 54 mg) followed by [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.015 mmol, 12.3 mg). The reaction mixture is heated using microwave radiation at 90° C. for 90 minutes. 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 residue is purified by reverse phase 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 and 2M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 397.

후처리

  1. temperatureThe reaction mixture is heated
  2. customat 90° C.
  3. customfor 90 minutes
  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 residue is purified by reverse phase 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 and 2M NH3 in MeOH
  13. concentrationconcentrated in vacuo
  14. customdried under vacuum

출처 및 근거

ORD 기록
ord-395e8167343446f2907ccd2ec23dbd14
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08343966B2

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