Sodium hydride → morpholine-4-carboxylic acid 6-(4-fluorophenyl)-5-oxo-7-(2-phenoxypyrimidin-4-yl)-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester

HRID 1581547ノート

反応式

HRID 1581547 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]2[CH2:15][CH:14]([O:16][C:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:18])[CH2:13][N:12]2[C:25]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([O:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:28]=2)=O)=[O:10])=[CH:4][CH:3]=1.[H-].[Na+]>CN(C)C=O.O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:10])[N:11]3[CH2:15][CH:14]([O:16][C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH2:13][N:12]3[C:25]=2[C:27]2[CH:32]=[CH:31][N:30]=[C:29]([O:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[N:28]=2)=[CH:4][CH:3]=1

参加物

5

反応物 2

HCID 24758Sodium hydrideHCID 20724735Morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-2-(2-phenoxypyrimidine-4-carbonyl)-pyrazolidin-4-yl ester

生成物 1

HCID 10118690morpholine-4-carboxylic acid 6-(4-fluorophenyl)-5-oxo-7-(2-phenoxypyrimidin-4-yl)-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester収率 32%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A solution of morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-2-(2-phenoxypyrimidine-4-carbonyl)-pyrazolidin-4-yl ester, 42, (154 mg, 0.287 mmol) in dimethylformamide (3 mL) is added dropwise to a −10° C. suspension of sodium hydride (16.4 mg of a 60% dispersion in mineral oil, 0.410 mmol) in tetrahydrofuran (3 mL). After 1 hour at −10° C., the reaction was warmed to 0° C. for 2 hours. The orange-colored solution is then quenched by slowly adding saturated NH4Cl (400 μL). The cooling bath is removed, and the solution allowed to warm to room temperature. The reaction mixture is concentrated in vacuo and the resulting residue is dissolved in THF (25 mL) and filtered through a pad of Celite. The filtrate is concentrated in vacuo and the residue purified by Prep HPLC to afford 47 mg (32% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.46 (d, J=4.9 Hz, 1H), 7.47-7.18 (m, 9H), 7.08 (t, J=8.7 Hz, 2H), 6.89 (d, J=4.9 Hz, 1H), 5.66 (m, 1H), 4.16 (m, 2H), 4.02 (d, J=12.9 Hz, 1H), 3.87 (dd, J=12.9, 5.1 Hz, 1H), 3.79-3.30 (m, 8H); HRMS m/z calcd for C27H25FN5O5 (MH+) 518.1840, found 518.1815.

後処理

  1. customThe orange-colored solution is then quenched by slowly adding saturated NH4Cl (400 μL)
  2. customThe cooling bath is removed
  3. temperatureto warm to room temperature
  4. concentrationThe reaction mixture is concentrated in vacuo
  5. dissolutionthe resulting residue is dissolved in THF (25 mL)
  6. filtrationfiltered through a pad of Celite
  7. concentrationThe filtrate is concentrated in vacuo
  8. customthe residue purified by Prep HPLC

出典と根拠

ORDレコード
ord-f87657aaf2dd46d6b3d2e8dd4717eb0b
出典データセット
uspto-grants-2004_05
特許番号
US06730668B2

反応ノート

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