4-Fluorobenzoic Acid → HCID 178489757、化合物

HRID 1092008

反応式

HRID 1092008 の反応式
C(Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1.CCN(C(C)C)C(C)C.[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH2:36][CH2:37][C:38]2[CH:39]=[C:40]([NH2:43])[NH:41][N:42]=2)[CH:31]=[C:32]([O:34][CH3:35])[CH:33]=1>ClCCl.CN(C=O)C>[CH3:35][O:34][C:32]1[CH:31]=[C:30]([CH2:36][CH2:37][C:38]2[CH:39]=[C:40]([NH:43][C:12](=[O:14])[C:11]3[CH:10]=[CH:9][C:8]([F:7])=[CH:16][CH:15]=3)[NH:41][N:42]=2)[CH:29]=[C:28]([O:27][CH3:26])[CH:33]=1

参加物

7

反応物 4

HCID 99734-Fluorobenzoic AcidHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 178489815HCID 178489815、化合物

生成物 1

HCID 178489757HCID 178489757、化合物収率 3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒3 回

反応条件

温度
0 °C

実験手順

Oxalyl chloride (2M in DCM, 1.40 ml, 2.75 mmol, 1.1 eq) was added dropwise to a mixture of 4-fluorobenzoic acid (350 mg, 2.50 mmol, 1 eq) in dichloromethane (15 ml) at 0° C. containing a few drops of DMF (10 ul, 0.12 mmol, 0.05 eq) and DIPEA (937 μl, 5.25 mmol, 2.1 eq). After stirring for 60 mins at 0° C. a solution of 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (742 mg, 3 mmol, 1.2 eq) in DCM (10 ml) was added dropwise over 15 mins. The mixture was maintained at 0° C. for a further 2 h, then gradually allowed to warm to room temperature overnight. The mixture was diluted with DCM (50 ml) and washed with aqueous NaHCO3 solution (50 ml). The aqueous layer was extracted with DCM (50 ml). The combined organic layers were collected and concentrated. The crude product was purified by reverse-phase prep HPLC using a 30-50% gradient of acetonitrile in water containing 1% ammonium hydroxide solution. The desired fractions were evaporated to afford the title compound as a beige solid. (31.5 mg, 3% yield)

後処理

  1. additionwas added dropwise over 15 mins
  2. temperatureto warm to room temperature overnight
  3. washwashed with aqueous NaHCO3 solution (50 ml)
  4. extractionThe aqueous layer was extracted with DCM (50 ml)
  5. customThe combined organic layers were collected
  6. concentrationconcentrated
  7. customThe crude product was purified by reverse-phase prep HPLC
  8. customThe desired fractions were evaporated

出典と根拠

ORDレコード
ord-256d18a37524478297e73a184d4cd89b
出典データセット
uspto-grants-2012_03
特許番号
US08129391B2

関連ノート

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