Cesium carbonate → 3-[({5-[(4-Fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrile

HRID 571732

반응식

HRID 571732 반응식
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([N:20]2[CH2:25][CH2:24][N:23]3[N:26]=[C:27]([OH:29])[CH:28]=[C:22]3[CH2:21]2)=[O:19])=[CH:14][CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.O>[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([N:20]2[CH2:25][CH2:24][N:23]3[N:26]=[C:27]([O:29][CH2:2][C:3]4[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=4)[C:6]#[N:7])[CH:28]=[C:22]3[CH2:21]2)=[O:19])=[CH:14][CH:13]=1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 178519627HCID 178519627, 화합물

생성물 1

HCID 727032163-[({5-[(4-Fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrile수율 59.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

실험 절차

3-(bromomethyl)benzonitrile (0.086 g, 0.44 mmol) was added to a stirred suspension of 5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ol (0.105 g, 0.4 mmol) and Cs2CO3 (0.261 g, 0.8 mmol) in ACN (2 mL). The mixture was stirred at room temperature for 16 hours, then diluted with water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected, the solvents evaporated in vacuo and the residue triturated with DIPE to yield 3-[({5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrile (0.089 g, 59% yield) as a white solid. C21H17FN4O2. 1H NMR (500 MHz, CDCl3) δ ppm 4.08 (br. s., 4 H), 4.74 (br. s., 2 H), 5.22 (s, 2 H), 5.51 (br. s., 1 H), 7.15 (t, J=8.5 Hz, 2 H), 7.44-7.51 (m, 3 H), 7.60 (d, J=7.8 Hz, 1 H), 7.65 (d, J=7.8 Hz, 1 H), 7.74 (s, 1 H).

후처리

  1. extractionextracted with DCM
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvents evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
  7. customThe desired fractions were collected
  8. customthe solvents evaporated in vacuo
  9. customthe residue triturated with DIPE

출처 및 근거

ORD 기록
ord-01c8c94e1b9646b7944fc260fa3cbca8
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029366B2

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