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

反応式

HRID 383573 の反応式
[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

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-308e5bef9c7f427f972533c1ae6a1c9d
出典データセット
uspto-grants-2013_02
特許番号
US08367671B2

関連ノート

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