1H-1,2,4-Triazole, 1-methyl- → 3-(4-Bromo-2-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1660744노트

반응식

HRID 1660744 반응식
C([Li])CCC.[CH3:6][N:7]1[CH:11]=[N:10][CH:9]=[N:8]1.Br[C:13]1[S:14][C:15]([C:19]2[C:20]([CH3:34])=[N:21][N:22]3[C:27]([CH:28]([CH2:31][CH3:32])[CH2:29][CH3:30])=[CH:26][C:25]([CH3:33])=[N:24][C:23]=23)=[C:16]([Br:18])[N:17]=1>C1COCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[Br:18][C:16]1[N:17]=[C:13]([C:11]2[N:7]([CH3:6])[N:8]=[CH:9][N:10]=2)[S:14][C:15]=1[C:19]1[C:20]([CH3:34])=[N:21][N:22]2[C:27]([CH:28]([CH2:29][CH3:30])[CH2:31][CH3:32])=[CH:26][C:25]([CH3:33])=[N:24][C:23]=12

참가 물질

7

반응물 3

HCID 224591H-1,2,4-Triazole, 1-methyl-HCID 674295502,4-Dibromo-5-(2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiazoleHCID 178418339Butyllithium

생성물 1

HCID 248989763-(4-Bromo-2-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine수율 33.4%

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

Under nitrogen atmosphere, add n-butyl lithium (2.5 M in hexane, 0.6 mL, 1.5 mmol) to a solution of 1-methyl-1,2,4-triazole (124.5 mg, 1 5 mmol) in THF (3 mL) at −78° C. and stir for 30 min. Add anhydrous zinc chloride (409 mg, 3 0 mmol), continue stirring for 30 min, warm up to room temperature and stir for 2 h. Add 3-(2,4-dibromo-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (229 mg, 0.5 mmol), followed by tetrakis(triphenylphosine)palladium (58 mg, 0.05 mmol) and reflux overnight. Cool to room temperature, dilute with ethyl acetate, and wash with saturated ammonia chloride. Dry the organic portion over sodium sulfate, filter, and concentrate to a residue. Purify the crude material by flash chromatography, eluting with hexanes:ethyl acetate (10:2.5) to give the title compound as a yellow foam (77 mg). MS (APCI) m/z (79Br) 460.4 (M+1)+.

후처리

  1. stirringstir for 2 h
  2. temperaturereflux overnight
  3. temperatureCool to room temperature
  4. washwash with saturated ammonia chloride
  5. dry with materialDry the organic portion over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate to a residue
  8. customPurify the crude material by flash chromatography
  9. washeluting with hexanes:ethyl acetate (10:2.5)

출처 및 근거

ORD 기록
ord-ae9514e516a14f6fbdd45ef397009a19
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030304B2

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