P-Cresol → 5-(4-fluorophenyl)-2-(p-tolyloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

HRID 2046211ノート

反応式

HRID 2046211 の反応式
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][N:27]3[N:30]=[C:31]([CH2:33][OH:34])[CH:32]=[C:26]3[C:25]2=[O:35])=[CH:20][CH:19]=1.[CH:36]1[C:41](O)=[CH:40][CH:39]=[C:38]([CH3:43])[CH:37]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.CCOC(C)=O>[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][N:27]3[N:30]=[C:31]([CH2:33][O:34][C:41]4[CH:40]=[CH:39][C:38]([CH3:43])=[CH:37][CH:36]=4)[CH:32]=[C:26]3[C:25]2=[O:35])=[CH:20][CH:19]=1

参加物

7

反応物 4

HCID 2879P-Cresol2 回HCID 11776Triphenylphosphine2 回HCID 97268Di-tert-butyl azodicarboxylate2 回HCID 679743405-(4-Fluoro-phenyl)-2-hydroxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

生成物 1

HCID 574100275-(4-fluorophenyl)-2-(p-tolyloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one収率 38.4%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Di-tert-butyl azodicarboxylate (0.027 g, 1.2 mmol) was added portionwise to a stirred solution of 5-(4-fluoro-phenyl)-2-hydroxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (104 mg, 0.4 mmol), p-cresol (0.13 mL, 1.2 mmol) and triphenylphosphine (0.31 g, 1.2 mmol) in THF (2 mL) at 0° C. The mixture was stirred at room temperature for 16 hours. More di-tert-butyl azodicarboxylate (0.027 g, 1.2 mmol), p-cresol (0.13 mL, 1.2 mmol) and triphenylphosphine (0.31 g, 1.2 mmol) were added at 0° C. and the mixture was stirred at 130° C. for 20 minutes. The mixture was diluted with AcOEt and washed with a 10% solution of NaOH. The organic layer was separated, dried (Na2SO4), filtered and the solvent was evaporated in vacuo. The crude product was purified by open column chromatography (silica; AcOEt in DCM 0/100 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo. The crude product was dissolved in a mixture of TFA (2.5 mL) and DCM (2.5 mL) and stirred at room temperature for 2 days. The mixture was basified with a saturated solution of Na2CO3 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 100/0). The desired fractions were collected and the solvents evaporated in vacuo. The product was triturated with DIPE to yield 5-(4-fluorophenyl)-2-(p-tolyloxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (54 mg, 38% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 2.29 (s, 3H), 4.16 (dd, J=6.8, 5.3 Hz, 2H), 4.53 (dd, J=6.9, 5.2 Hz, 2H), 5.09 (s, 2H), 6.90 (d, J=8.7 Hz, 2H), 7.01 (s, 1H), 7.09 (d, J=8.4 Hz, 2H), 7.13 (t, J=8.7 Hz, 2H), 7.28-7.35 (m, 2H).

後処理

  1. stirringthe mixture was stirred at 130° C. for 20 minutes
  2. washwashed with a 10% solution of NaOH
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated in vacuo
  7. customThe crude product was purified by open column chromatography (silica; AcOEt in DCM 0/100 to 20/80)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo
  10. dissolutionThe crude product was dissolved in a mixture of TFA (2.5 mL) and DCM (2.5 mL)
  11. stirringstirred at room temperature for 2 days
  12. extractionextracted with DCM
  13. customThe organic layer was separated
  14. dry with materialdried (MgSO4)
  15. filtrationfiltered
  16. customthe solvents evaporated in vacuo
  17. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 100/0)
  18. customThe desired fractions were collected
  19. customthe solvents evaporated in vacuo
  20. customThe product was triturated with DIPE

出典と根拠

ORDレコード
ord-7a38a2742f744a438681c78021c346b5
出典データセット
uspto-grants-2013_11
特許番号
US08592422B2

反応ノート

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