Phenolate Sodium → 2-(4-fluorophenyl)-6-hydroxy-3-(2-phenoxypyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

HRID 1581541

反応式

HRID 1581541 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:33])[N:10]3[CH2:25][CH:24]([O:26]C(=O)C(C)(C)C)[CH2:23][N:11]3[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15](S(C)(=O)=O)[N:14]=2)=[CH:4][CH:3]=1.[C:34]1([O-:40])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:33])[N:10]3[CH2:25][CH:24]([OH:26])[CH2:23][N:11]3[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([O:40][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:14]=2)=[CH:4][CH:3]=1

参加物

4

反応物 2

HCID 4445035Phenolate SodiumHCID 207247412,2-dimethyl-propionic acid 6-(4-fluorophenyl)-7-(2-methane-sulfonyl-pyrimidin-4-y)-5-oxo-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester

生成物 1

HCID 102725602-(4-fluorophenyl)-6-hydroxy-3-(2-phenoxypyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one収率 21%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of 2,2-dimethyl-propionic acid 6-(4-fluorophenyl)-7-(2-methane-sulfonyl-pyrimidin-4-yl)-5-oxo-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester, 35, (50 mg, 0.105 mmol) in THF (1 mL) is slowly cannulated into a solution of sodium phenolate in THF (1 mL) at 0° C. The cooling bath is removed and the reaction stirred at room temperature for 1 hour. The reaction is quenched with NH4Cl (sat. aq.) (500 μL). The reaction mixture is concentrated in vacuo and the residue diluted taken up in ethyl acetate (15 mL). The solution is washed with water (20 mL) and a 5% aqueous Na2CO3 (20 mL). The combined aqueous layers are extracted with ethyl acetate (25 mL) and brine (20 mL), dried, filtered and concentrated in vacuo. The crude material is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate) to afford 9 mg (21% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.43 (d, J=5.2 Hz, 1H), 7.46 (t, J=7.8 Hz, 2H), 7.31-7.27 (m, 3H), 7.19 (d, J=8.2 Hz, 2H), 7.03 (t, J=8.6 Hz, 2H), 6.80 (d, J=5.2 Hz, 1H), 5.41 (br s, 1H), 4.82 (m, 1H), 4.23 (d, J=12.4 Hz, 1H), 3.95-3.85 (m, 2H), 3.76 (dd, J=12.4, 4.4 Hz, 1H); HRMS m/z calcd for C22H18FN4O3 (MH+) 405.1363, found 405.1365.

後処理

  1. customThe cooling bath is removed
  2. customThe reaction is quenched with NH4Cl (sat. aq.) (500 μL)
  3. concentrationThe reaction mixture is concentrated in vacuo
  4. additionthe residue diluted
  5. washThe solution is washed with water (20 mL)
  6. extractionThe combined aqueous layers are extracted with ethyl acetate (25 mL) and brine (20 mL)
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate)

出典と根拠

ORDレコード
ord-ce01f486bc7c46188b91dfcff743f6a9
出典データセット
uspto-grants-2004_05
特許番号
US06730668B2

関連ノート

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