2,2-Dimethoxypropane → HCID 86662299、化合物

HRID 2364053ノート

反応式

HRID 2364053 の反応式
Br[C:2]1[S:6][C:5]([C:7]([NH2:9])=[O:8])=[C:4]([NH:10][CH2:11][CH:12]([F:14])[F:13])[CH:3]=1.CO[C:17](OC)([CH3:19])[CH3:18].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+].[CH3:48][C:49]1[C:53](B2OC(C)(C)C(C)(C)O2)=[CH:52][N:51](C(OC(C)(C)C)=O)[N:50]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.COCCOC.CCOC(C)=O.CC(N(C)C)=O>[F:13][CH:12]([F:14])[CH2:11][N:10]1[C:4]2[CH:3]=[C:2]([C:53]3[CH:52]=[N:51][NH:50][C:49]=3[CH3:48])[S:6][C:5]=2[C:7](=[O:8])[NH:9][C:17]1([CH3:19])[CH3:18]

参加物

12

反応物 7

HCID 64952,2-DimethoxypropaneHCID 10340Sodium CarbonateHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 53216815Tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrazole-1-carboxylateHCID 866622985-Bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxamide

生成物 1

HCID 86662299HCID 86662299、化合物収率 52%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
90 °C

実験手順

A mixture of 5-bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxamide (130 mg, 0.456 mmol), 2,2-dimethoxypropane (1 mL), CSA (11 mg, 0.046 mmol), MgSO4 (110 mg, 0.912 mmol) and DMA (1 mL) was stirred at 90° C. for 2 h. Then, saturated aqueous NaHCO3 and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, a colorless crystalline solid was obtained. A flask was charged with the solid, 1,2-dimethoxyethane (3.0 mL), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (422 mg, 1.37 mmol), sodium carbonate (137 mg, 2.28 mmol) and water (1.5 mL). The flask was purged with argon. Then, 1,1′-bis (diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (37 mg, 0.046 mmol) was added to the mixture. The flask was purged with argon. After stirring at 100° C. for 2 h, 8 M aqueous NaOH (0.5 mL) was added. After stirring at 100° C. for 1 h, the organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc), then crystallized from EtOAc/hexane to give the title compound (78 mg, 52%) as a yellow solid:

後処理

  1. customto quench
  2. customthe reaction
  3. extractionThe organic materials were extracted with EtOAc
  4. washThe combined extracts were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customAfter removal of the solvent at reduced pressure
  8. customa colorless crystalline solid was obtained
  9. customThe flask was purged with argon
  10. customThe flask was purged with argon
  11. stirringAfter stirring at 100° C. for 2 h
  12. addition8 M aqueous NaOH (0.5 mL) was added
  13. stirringAfter stirring at 100° C. for 1 h
  14. extractionthe organic materials were extracted with EtOAc
  15. washThe combined extracts were washed with brine
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. customAfter removal of the solvent at reduced pressure
  19. customthe residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc)
  20. customcrystallized from EtOAc/hexane

出典と根拠

ORDレコード
ord-8cbe7a8e64b24d6cbf34ddede8e5bd9a
出典データセット
uspto-grants-2014_04
特許番号
US08691828B2

反応ノート

読み込み中…