4-Fluorobenzoic Acid → HCID 178489757, 화합물

HRID 16737

반응식

HRID 16737 반응식
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

참가 물질

7

반응물 4

HCID 99734-Fluorobenzoic AcidHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 178489815HCID 178489815, 화합물

생성물 1

HCID 178489757HCID 178489757, 화합물수율 3%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매3회

반응 조건

온도
0 °C

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-1e71506f710044cbbbadcf5045c78d46
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737149B2

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