Methyl iodide → (S)-5-(4-fluoro-phenyl)-6-methoxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

HRID 2046193ノート

反応式

HRID 2046193 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@H:13]([CH2:14][OH:15])[CH2:12][N:11]3[N:16]=[C:17]([CH2:19][O:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH:18]=[C:10]3[C:9]2=[O:27])=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:31]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@H:13]([CH2:14][O:15][CH3:31])[CH2:12][N:11]3[N:16]=[C:17]([CH2:19][O:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:18]=[C:10]3[C:9]2=[O:27])=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67974066(S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

生成物 1

HCID 67974416(S)-5-(4-fluoro-phenyl)-6-methoxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one収率 65.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

A solution of (S)-5-(4-fluoro-phenyl)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (0.135 g, 0.36 mmol) in THF (0.5 mL) was added to a suspension of a 60% dispersion of sodium hydride in mineral oils (17 mg, 0.44 mmol) in THF (0.5 mL) at 0° C. The mixture was stirred for 10 minutes at 0° C., then iodomethane (0.046 mL, 0.73 mmol) was added. The reaction was heated at 120° C. for 10 minutes under microwave irradiation. Then the mixture was quenched with a saturated solution of NH4Cl and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The residue was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80). Desired fractions were collected and the solvents evaporated in vacuo. The residue was triturated with DIPE to yield (S)-5-(4-fluoro-phenyl)-6-methoxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (90 mg, 64% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 3.26 (s, 3H), 3.36 (t, J=9.2 Hz, 1H), 3.51 (dd, J=9.5, 3.9 Hz, 1H), 4.21 (dtd, J=9.0, 4.5, 4.5, 2.3 Hz, 1H), 4.59 (dd, J=13.3, 4.7 Hz, 1H), 4.74 (dd, J=13.3, 2.2 Hz, 1H), 5.13 (s, 2H), 6.94-7.00 (m, 1H), 7.00-7.04 (m, 3H), 7.10-7.19 (m, 2H), 7.27-7.36 (m, 4H).

後処理

  1. temperatureThe reaction was heated at 120° C. for 10 minutes under microwave irradiation
  2. customThen the mixture was quenched with a saturated solution of NH4Cl
  3. extractionextracted with AcOEt
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvents evaporated in vacuo
  8. customThe residue was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80)
  9. customDesired fractions were collected
  10. customthe solvents evaporated in vacuo
  11. customThe residue was triturated with DIPE

出典と根拠

ORDレコード
ord-c73544a53b1648849241ac4a1c012be3
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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