Triethylamine → 3-(1-(2,4-difluorophenyl)-7-ethyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-N-(isoxazol-3-yl)-4-methylbenzamide

HRID 383573

반응식

HRID 383573 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17]2[N:16]([CH2:18][CH3:19])[C:15](=[O:20])[C:14]([C:21]3[CH:22]=[C:23]([CH:27]=[C:28]([F:31])[C:29]=3[CH3:30])[C:24]([OH:26])=O)=[N:13][C:12]=2[CH:11]=[N:10]1.C(Cl)(=O)C(Cl)=O.[NH2:38][C:39]1[CH:43]=[CH:42][O:41][N:40]=1.CCN(CC)CC.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17]2[N:16]([CH2:18][CH3:19])[C:15](=[O:20])[C:14]([C:21]3[CH:22]=[C:23]([CH:27]=[C:28]([F:31])[C:29]=3[CH3:30])[C:24]([NH:38][C:39]3[CH:43]=[CH:42][O:41][N:40]=3)=[O:26])=[N:13][C:12]=2[CH:11]=[N:10]1

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 18102163-IsoxazolamineHCID 671996043-(1-(2,4-difluorophenyl)-7-ethyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-4-methylbenzoic acid

생성물 1

HCID 671981413-(1-(2,4-difluorophenyl)-7-ethyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-N-(isoxazol-3-yl)-4-methylbenzamide

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

A solution of 3-(1-(2,4-difluorophenyl)-7-ethyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-4-methylbenzoic acid (360 mg, 0.84 mmol) in 5.0 mL of DCM was treated with oxalyl chloride (0.84 mL of 2.0 M in DCM solution, 1.68 mmol) followed by two drops of DMF while cooling in an ice bath at 0° C. It was stirred at this temperature for 15 min then allowed to stir at RT for 45 min. The reaction mixture was then concentrated under reduce pressure to remove the excess oxalyl chloride. The residue was dissolved in 5.0 mL of DCM, treated with 3-aminoisoxazole (212 mg, 2.52 mmol) followed by Et3N (0.18 mL, 1.26 mmol) and stirred for 18 h. The reaction mixture was treated with 15 mL saturated NaHCO3 and extracted with DCM (2×15 mL). The combined DCM layers were dried over MgSO4. Purification on the ISCO (12 g column, 20-70% EtOAc in hexanes) afforded 3-(1-(2,4-difluorophenyl)-7-ethyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-N-(isoxazol-3-yl)-4-methylbenzamide as a light yellow amorphous solid. MS (ES+): 495.1 (M+H)+.

후처리

  1. stirringto stir at RT for 45 min
  2. concentrationThe reaction mixture was then concentrated
  3. customto remove the excess oxalyl chloride
  4. dissolutionThe residue was dissolved in 5.0 mL of DCM
  5. stirringstirred for 18 h
  6. extractionextracted with DCM (2×15 mL)
  7. dry with materialThe combined DCM layers were dried over MgSO4
  8. customPurification on the ISCO (12 g column, 20-70% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-308e5bef9c7f427f972533c1ae6a1c9d
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367671B2

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