2-Aminopropanediamide → ethyl 5-carbamoyl-4-(3-fluoro-4-nitrophenyl)-1H-pyrrole-3-carboxylate

HRID 73652ノート

反応式

HRID 73652 の反応式
C[N:2]([CH3:22])[CH:3]=[C:4]([C:10](=O)[C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[C:13]([F:20])[CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].NC(C(N)=O)[C:25]([NH2:27])=[O:26]>CC(O)=O>[NH2:27][C:25]([C:22]1[NH:2][CH:3]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[C:13]([F:20])[CH:12]=1)=[O:26]

参加物

4

反応物 2

HCID 964572-AminopropanediamideHCID 66640928Ethyl 2-(3-fluoro-4-nitrobenzoyl)-3-(dimethylamino)acrylate

生成物 1

HCID 57955150ethyl 5-carbamoyl-4-(3-fluoro-4-nitrophenyl)-1H-pyrrole-3-carboxylate収率 69%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
80 °C

実験手順

A 50 mL round bottomed flask was charged with of ethyl 3-(dimethylamino)-2-(3-fluoro-4-nitrobenzoyl)acrylate (51.74 g, 166.75 mmol) and 2-aminomalonamide (23.4 mg, 200 mmol) and AcOH (1 L). The reaction mixture was heated to 80° C. over night. The starting material appeared consumed by TLC. The AcOH was removed under reduced pressure and TFA (300 mL) was added. The mixture was heated over night at 60° C. The reaction was cooled to room temperature and the TEA was removed under reduced pressure. The orange oil was treated with saturated aqueous NaHCO3 (1 L), then solid NaHCO3 was added until the solution was neutral. The solids were filtered and placed in a 1 L erlenmeyer flask. The solids were washed with H2O (3×1 L) and the water was decanted off through the filter. On the last washing the solids were poured onto the filter and allowed to air dry. The solids were once again removed from the filter and washed with Et2O (4×500 mL). The Et2O was decanted off through the filter and on the final washing the solids were transferred to the filter. An addition portion of Et2O (200 mL) was used to wash the flask and the filter cake. The desired product was dried in a vacuum oven at 40° C. to provide a light tan solid (36.8 g, 114.5 mmol, 69% yield). 1H-NMR (DMSO-d6) δ 12.28 (br s, 1H), 8.07 (app t, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.46 (dd, J=12.6, 1.6 Hz, 1H), 7.28 (dd, J=8.4, 1.6 Hz, 1H), 7.25 (br s, 1H), 6.72 (br s, 1H), 4.01 (q, J=7.2 Hz, 2H), 1.07 (t, J=7.2 Hz, 3H); LCMS* RT=4.45 min; MS {M−H]+=320.1.

後処理

  1. customThe starting material appeared consumed by TLC
  2. customThe AcOH was removed under reduced pressure and TFA (300 mL)
  3. additionwas added
  4. temperatureThe mixture was heated over night at 60° C
  5. temperatureThe reaction was cooled to room temperature
  6. customthe TEA was removed under reduced pressure
  7. additionThe orange oil was treated with saturated aqueous NaHCO3 (1 L)
  8. additionsolid NaHCO3 was added until the solution
  9. filtrationThe solids were filtered
  10. customplaced in a 1 L erlenmeyer flask
  11. washThe solids were washed with H2O (3×1 L)
  12. customthe water was decanted off through the filter
  13. washOn the last washing the solids
  14. additionwere poured onto the
  15. filtrationfilter
  16. customto air dry
  17. customThe solids were once again removed from the
  18. filtrationfilter
  19. washwashed with Et2O (4×500 mL)
  20. customThe Et2O was decanted off through the
  21. filtrationfilter
  22. washon the final washing the solids
  23. washto wash the flask
  24. dry with materialThe desired product was dried in a vacuum oven at 40° C.

出典と根拠

ORDレコード
ord-5424cac102ee4bc8b6238f62ffc8df8d
出典データセット
uspto-grants-2014_09
特許番号
US08829185B2

反応ノート

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