Potassium Carbonate → {5-Amino-3-tert-butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-3'-yl}-methanol

HRID 60676

反応式

HRID 60676 の反応式
I[C:2]1[C:3]([CH2:16][OH:17])=[N:4][N:5]([CH2:7][CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[CH:6]=1.[C:18]([C:22]1[CH:26]=[C:25]([NH2:27])[NH:24][N:23]=1)([CH3:21])([CH3:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>C1(C)C(C)=CC=CC=1.O.[OH-].[NH4+].CCOC(C)=O.[Cu]I>[NH2:27][C:25]1[N:24]([C:2]2[C:3]([CH2:16][OH:17])=[N:4][N:5]([CH2:7][CH2:8][O:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][O:11]3)[CH:6]=2)[N:23]=[C:22]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:26]=1

参加物

10

反応物 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 117729333HCID 117729333、化合物HCID 178441179HCID 178441179、化合物

生成物 1

HCID 117729489{5-Amino-3-tert-butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4']bipyrazolyl-3'-yl}-methanol収率 63%

試薬・触媒・溶媒 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒2 回HCID 962Water溶媒HCID 7237O-Xylene溶媒HCID 8857Ethyl Acetate溶媒HCID 14923Ammonium Hydroxide溶媒

反応条件

温度
150 °C

実験手順

A solution of Intermediate 74d (0.51 g, 1.45 mmol) in xylene (2.4 mL) was treated with 3-(tert-butyl)-1H-pyrazol-5-amine (0.18 g, 1.32 mmol) then potassium carbonate (0.38 g, 2.76 mmol), trans-N,N′-Dimethyl-1,2-cyclohexanediamine (0.037 g, 0.26 mmol) and copper (I) iodide (0.013 g, 0.066 mmol) were added. The mixture was degassed then heated at 150° C. for 4 h using microwave irradiation. Another portion of copper (I) iodide (0.006 g, 0.03 mmol) was added and the reaction mixture heated at 150° C. for a further 2 h using microwave irradiation. The mixture was diluted with water (1 mL), conc. aqueous ammonium hydroxide (1 mL) and EtOAc (1 mL) and the phases separated. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-5% MeOH in DCM to give the title compound as a dark green gum (0.30 g, 63%). LCMS (Method 3): Rt 2.46 min, m/z 364 [MH+].

後処理

  1. customThe mixture was degassed
  2. custommicrowave irradiation
  3. temperaturethe reaction mixture heated at 150° C. for a further 2 h
  4. custommicrowave irradiation
  5. customthe phases separated
  6. extractionThe aqueous layer was then extracted with EtOAc (2×)
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue was purified by FCC

出典と根拠

ORDレコード
ord-f5b6f790c30f4ddf9b1104b6c9aeffe1
出典データセット
uspto-grants-2016_09
特許番号
US09440974B2

関連ノート

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