Dichloromethane → 5-Nitro-2-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine

HRID 1191228노트

반응식

HRID 1191228 반응식
Br[C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].C(Cl)Cl.[F:21][C:22]([F:33])([F:32])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)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]>[N+:9]([C:5]1[C:6]([NH2:8])=[CH:7][C:2]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[C:22]([F:33])([F:32])[F:21])=[N:3][CH:4]=1)([O-:11])=[O:10]

참가 물질

6

반응물 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 130404032-Bromo-5-nitropyridin-4-amine

생성물 1

HCID 674124155-Nitro-2-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine

시약·촉매·용매 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매

반응 조건

온도
85 °C

실험 절차

2-Bromo-5-nitropyridin-4-amine (561 mg, 2.57 mmol), Cs2CO3 (2.52 g, 7.72 mmol), (dppf)PdCl2.DCM (113 mg, 0.154 mmol), and 2-(trifluoromethyl)phenylboronic acid (636 mg, 3.35 mmol) were combined and flushed with Ar and anhydrous DME (24 mL) was added. H2O (8 mL) was added via syringe and the resulting mixture was stirred at 85° C. for 18 h. The resulting mixture was cooled to room temperature and diluted with EtOAc (30 mL) and the resulting solution was washed with brine (30 mL). The aqueous phase was extracted with EtOAc (3×25 mL) and the combined extracts were dried over MgSO4 and filtered. The solvent was removed under reduced pressure and the residue was chromatographed on a 40-g SiO2 pre-packed column eluting with 0:1-2:3 EtOAc/hexanes to yield 5-nitro-2-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine. 1H-NMR (400 MHz, CDCl3) δ: 9.17 (s, 1H), 7.70 (d, J=7.8 Hz, 1H), 7.56 (t, J=7.1 Hz, 1H), 7.49 (t, J=7.5 Hz, 1H), 7.40 (d, J=7.6 Hz, 1H), 7.00 (br. s., 2H), 6.71 (s, 1H). Mass Spectrum (LCMS, ESI pos.): Calculated for C12H8F3N3O2: 284.1 (M+H); Measured: 284.1.

후처리

  1. customflushed with Ar and anhydrous DME (24 mL)
  2. additionwas added
  3. additionH2O (8 mL) was added via syringe
  4. temperatureThe resulting mixture was cooled to room temperature
  5. additiondiluted with EtOAc (30 mL)
  6. washthe resulting solution was washed with brine (30 mL)
  7. extractionThe aqueous phase was extracted with EtOAc (3×25 mL)
  8. dry with materialthe combined extracts were dried over MgSO4
  9. filtrationfiltered
  10. customThe solvent was removed under reduced pressure
  11. customthe residue was chromatographed on a 40-g SiO2 pre-packed column
  12. washeluting with 0:1-2:3 EtOAc/hexanes

출처 및 근거

ORD 기록
ord-fc3591e3b7c44cc3b4f586b096d357a2
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680098B2

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