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 1660744ノート

反応式

HRID 1660744 の反応式
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

参加物

7

反応物 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

生成物 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]pyrimidine収率 33.4%

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-ae9514e516a14f6fbdd45ef397009a19
出典データセット
uspto-grants-2011_10
特許番号
US08030304B2

反応ノート

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