反応式
C(Cl)(=O)C(Cl)=O.[CH3:7][N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1.CCN(C(C)C)C(C)C.[CH2:32]([C:40]1[CH:41]=[C:42]([NH2:45])[NH:43][N:44]=1)[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(Cl)Cl>[CH3:7][N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:15]=[CH:16][C:17]([C:18]([NH:45][C:42]3[NH:43][N:44]=[C:40]([CH2:32][CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH:41]=3)=[O:20])=[CH:21][CH:22]=2)[CH2:12][CH2:13]1参加物
反応条件
- 温度
- 0 °C
実験手順
Oxalyl chloride (2M in DCM, 250 μl, 0.50 mmol, 1.1 eq) was added dropwise to a mixture of 4-(4-methylpiperazin-1-yl)benzoic acid (100 mg, 0.45 mmol, 1 eq) in DCM (5 ml, containing a few drops of DMF) and DIPEA (171 μl, 0.95 mmol, 2.1 eq) at O° C. After stirring for 1 h at 0° C., a solution of 5-phenethyl-2H-pyrazol-3-amine (128 mg, 0.68 mmol, 1.5 eq) in DCM (2 ml) was added dropwise. The mixture was maintained at 0° C. for 2 h, then gradually allowed to warm to room temperature overnight. The mixture was diluted with DCM (50 ml), washed with aq. NaHCO3 solution (50 ml) and the aqueous layer was extracted with DCM (50 ml). The combined organic layers were concentrated. The crude product was purified by reverse-phase prep. HPLC (basic) using a 30-50% gradient of acetonitrile in water (containing 1% ammonium hydroxide) to yield the title compound (8 mg, 3% yield).
後処理
- temperatureThe mixture was maintained at 0° C. for 2 h
- temperatureto warm to room temperature overnight
- washwashed with aq. NaHCO3 solution (50 ml)
- extractionthe aqueous layer was extracted with DCM (50 ml)
- concentrationThe combined organic layers were concentrated
- customThe crude product was purified by reverse-phase prep
出典と根拠
- ORDレコード
- ord-497ee524cd6c46a081af0d4567cf7fca
- 出典データセット
- uspto-grants-2010_06
- 特許番号
- US07737149B2
関連ノート
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