Pyridine → 5-(4-Fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazine

HRID 1773781ノート

反応式

HRID 1773781 の反応式
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[O:11]([CH2:18][C:19]1[CH:27]=[C:22]2[CH2:23][NH:24][CH2:25][CH2:26][N:21]2[N:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CC=CC=1>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:24]2[CH2:25][CH2:26][N:21]3[N:20]=[C:19]([CH2:18][O:11][C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)[CH:27]=[C:22]3[CH2:23]2)=[O:7])=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 1049PyridineHCID 678794-Fluorobenzoyl chlorideHCID 679582494,5,6,7-Tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazine

生成物 1

HCID 679583635-(4-Fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazine収率 59.8%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 10340Sodium Carbonate溶媒

実験手順

4-Fluorobenzoyl chloride (0.14 mL, 1.2 mmol) was added to a stirred solution of 4,5,6,7-tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazine (0.3 g, 1.0 mmol) and pyridine (0.16 mL, 2.0 mmol) in DCM (13 mL) under N2 at 0° C. The reaction was stirred at room temperature for 1 hour, diluted with a saturated solution of Na2CO3 and extracted with DCM. The organic layer was separated, dried (Na2SO4), 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 and the solvents evaporated in vacuo. The desired product was triturated with DIPE to yield 5-(4-fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazine (0.21 g, 59% yield) as a white solid. C20H18FN3O2 1H NMR (500 MHz, CDCl3) δ ppm 4.07 (br. s., 2H), 4.27 (br. s., 2H), 4.81 (br. s., 2H), 5.05 (s, 2H), 6.16 (br. s., 1H), 6.96 (dd, J=7.5, 7.2 Hz, 1H), 6.99 (d, J=8.4 Hz, 2H), 7.15 (t, J=8.5 Hz, 2H), 7.29 (dd, J=8.1, 7.8 Hz, 2H), 7.49 (dd, J=8.5, 5.3 Hz, 2H).

後処理

  1. extractionextracted with DCM
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  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 desired product was triturated with DIPE

出典と根拠

ORDレコード
ord-403016f88e734ce5b900290f92e46baf
出典データセット
uspto-grants-2016_02
特許番号
US09255103B2

反応ノート

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