Triethylamine → 5-fluoro-3-methyl-1H-pyrrolo[3,2-b]pyridine

HRID 2382137노트

반응식

HRID 2382137 반응식
[CH2:1]([N:4]([C:11]1[C:12](Br)=[N:13][C:14]([F:17])=[CH:15][CH:16]=1)C(=O)C(F)(F)F)[CH:2]=[CH2:3].[Cl-].C([NH3+])CCC.C([NH3+])CCC.C([NH3+])CCC.C([NH3+])CCC.[Cl-].[Cl-].[Cl-].C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:17][C:14]1[N:13]=[C:12]2[C:2]([CH3:3])=[CH:1][NH:4][C:11]2=[CH:16][CH:15]=1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 86639385N-allyl-N-(2-bromo-6-fluoro-pyridin-3-yl)-2,2,2-trifluoro-acetamideHCID 86639386Tetra(n-butylammonium) chloride

생성물 1

HCID 685551555-fluoro-3-methyl-1H-pyrrolo[3,2-b]pyridine수율 95.8%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

실험 절차

A solution of N-allyl-N-(2-bromo-6-fluoro-pyridin-3-yl)-2,2,2-trifluoro-acetamide (3.41 g, 10.43 mmol), palladium acetate (94 mg, 0.42 mmol), tetra(n-butylammonium) chloride (3.19 g, 11.47 mmol) and triethylamine (2.37 g, 23.4 mmol) in anhydrous DMF (20 mL) is stirred at 10° C. under N2 for an hour. DMF is evaporated off and the residue is mixed with water (12 mL) and stirred at rt for an hour. EtOAc (15 mL) is added and stirred at rt overnight. The organic layer is separated and the aqueous layer is extracted with EtOAc (35 mL). The combined organic layer is dried (Na2SO4), filtered, and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10-60% EtOAc in heptane to afford 5-fluoro-3-methyl-1H-pyrrolo[3,2-b]pyridine (1.5 g) as a solid. MS: 151 (M+H); 1H NMR (300 MHz, CDCl3) δ 2.38(s, 3H), 6.77(d, H), 7.28(s, H), 7.74(dd, H).

후처리

  1. customDMF is evaporated off
  2. additionthe residue is mixed with water (12 mL)
  3. additionEtOAc (15 mL) is added
  4. stirringstirred at rt overnight
  5. customThe organic layer is separated
  6. extractionthe aqueous layer is extracted with EtOAc (35 mL)
  7. dry with materialThe combined organic layer is dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by silica gel chromatography
  11. washeluting with 10-60% EtOAc in heptane

출처 및 근거

ORD 기록
ord-a28f914a70704e418dd39998762c6f20
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08258130B2

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