Dichloromethane → HCID 86647917, 화합물

HRID 1970945노트

반응식

HRID 1970945 반응식
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:10]2[CH:11]=[CH:12][C:13](B(O)O)=[N:14][CH:15]=2)[CH:7]=[CH:8][CH:9]=1.[Cl:19][C:20]1[CH:25]=[C:24](Cl)[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[N:21]=1.C(Cl)Cl>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].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]>[Cl:19][C:20]1[CH:25]=[C:24]([C:12]2[CH:13]=[N:14][CH:15]=[C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([O:3][CH3:2])[CH:5]=3)[CH:11]=2)[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[N:21]=1

참가 물질

7

반응물 3

HCID 6344DichloromethaneHCID 120574654,6-dichloro-2-(2-pyridinyl)pyrimidineHCID 67331136HCID 67331136, 화합물

생성물 1

HCID 86647917HCID 86647917, 화합물

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매HCID 10340Sodium Carbonate용매

실험 절차

A solution of 5-(3-methoxy-phenyl)-pyridine boronic acid hydrochloride (Int. D) (1 eq, 59 mg) in DME (1 ml) and 2M sodium carbonate (0.4 ml) is treated with 4,6-dichloro-2-pyridin-2-yl-pyrimidine (Int. C) (1 eq, 50 mg) and placed under an atmosphere of argon. PdCl2(dppf).DCM (0.1 eq. 16 mg) is added and the reaction mixture is heated using microwave radiation at 90° C. for 1 h. After cooling to room temperature, the mixture is partitioned between EtOAc/water and the organic portion is separated, washed with brine, dried (MgSO4) and concentrated in vacuo. The crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% TFA) and the appropriate fractions are combined and concentrated in vacuo. The residue is loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are concentrated in vacuo and dried under vacuum overnight to afford the title compound [M+H]+=375/377.

후처리

  1. temperaturethe reaction mixture is heated
  2. customat 90° C.
  3. customfor 1 h
  4. customthe mixture is partitioned between EtOAc/water
  5. customthe organic portion is separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% TFA)
  10. concentrationconcentrated in vacuo
  11. washeluting with MeOH
  12. concentrationThe methanolic ammonia fractions are concentrated in vacuo
  13. customdried under vacuum overnight

출처 및 근거

ORD 기록
ord-ec8f9c9cd6dc480e92e99b2aff1d680f
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431578B2

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