N,N-Dimethylglycine → 5-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

HRID 2046210ノート

反応式

HRID 2046210 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([CH2:17][OH:18])[CH:16]=[C:10]3[C:9]2=[O:19])=[CH:4][CH:3]=1.Br[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O>O1CCOCC1.CCOC(C)=O.[Cu]I>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([CH2:17][O:18][C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:16]=[C:10]3[C:9]2=[O:19])=[CH:4][CH:3]=1

参加物

8

反応物 4

HCID 673N,N-Dimethylglycine2 回HCID 10796Cesium carbonate2 回HCID 122863-BromopyridineHCID 679743405-(4-Fluoro-phenyl)-2-hydroxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

生成物 1

HCID 574101415-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one収率 11%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

Copper (I) iodide (7.3 mg, 0.038 mmol) was added to a stirred suspension of 5-(4-fluoro-phenyl)-2-hydroxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (50 mg, 0.19 mmol), 3-bromopyridine (0.073 mL, 0.76 mmol), cesium carbonate (0.25 g, 0.77 mmol) and N,N-dimethylglycine (7.89 mg, 0.077 mmol) in 1,4-dioxane (1 mL) in a sealed tube and under nitrogen. The mixture was stirred at 100° C. for 16 hours. More copper (I) iodide (7.3 mg, 0.038 mmol) was added, N,N-dimethylglycine (7.89 mg, 0.077 mmol), cesium carbonate (0.25 g, 0.77 mmol) 3-bromopyridine (0.073 mL, 0.76 mmol) were added and the mixture was stirred at 130° C. for another 24 hours. The mixture was diluted with AcOEt and washed with a 16% aqueous solution of NH4OH. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 5/95). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (7 mg, 11% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 4.13-4.22 (m, 2H), 4.55 (dd, J=6.8, 5.3 Hz, 2H), 5.17 (s, 2H), 7.03 (s, 1H), 7.10-7.18 (m, 2H), 7.23 (dd, J=8.5, 4.8 Hz, 1H), 7.28-7.36 (m, 3H), 8.25 (dd, J=4.6, 1.2 Hz, 1H), 8.41 (d, J=2.9 Hz, 1H).

後処理

  1. stirringthe mixture was stirred at 130° C. for another 24 hours
  2. washwashed with a 16% aqueous solution of NH4OH
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in MeOH in DCM 0/100 to 5/95)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

出典と根拠

ORDレコード
ord-8d34fac4b71c436ea08008038d99e6b2
出典データセット
uspto-grants-2013_11
特許番号
US08592422B2

反応ノート

読み込み中…