Diisopropylamine → 7-bromo-5-fluoro-1H-indole-2-carboxylic Acid 3-methoxy-benzylamide

HRID 500433

反応式

HRID 500433 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([F:14])[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([OH:13])=O)=[CH:7]2.[CH3:15][O:16]NCC1C=CC=CC=1.C1CN([P+](ON2N=N[C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][C:43]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH:58]([NH:61]C(C)C)(C)C>C(OCC)(=O)C>[CH3:15][O:16][C:48]1[CH:43]=[C:44]([CH:45]=[CH:46][CH:47]=1)[CH2:58][NH:61][C:11]([C:8]1[NH:9][C:10]2[C:6]([CH:7]=1)=[CH:5][C:4]([F:14])=[CH:3][C:2]=2[Br:1])=[O:13]

参加物

6

反応物 4

HCID 7912DiisopropylamineHCID 2724699PyBOPHCID 11815413Benzyl(methoxy)amineHCID 219043557-bromo-5-fluoro-1H-indole-2-carboxylic acid

生成物 1

HCID 210144567-bromo-5-fluoro-1H-indole-2-carboxylic Acid 3-methoxy-benzylamide収率 81%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a round bottom flask that has been fire dried, flushed with a continuous stream of argon, and equipped with a stir bean, DMF (4.8 ml) was added. To this stirring solution 5 (600 mg, 2.33 mmol), was combined with methoxybenzylamine (328 μL, 2.56 mmol), and PyBOP (1.33 g, 2.56 mmol). This solution was then cooled to a temperature of 0 degrees C. After 2 minutes diisopropylamine (1.7 ml, 9.67 mmol) was added and the entire solution was allowed to stir at room temperature overnight. The reaction was then diluted with roughly 60 ml of ethyl acetate and extracted 3× with saturated sodium bicarbonate, and 3× with 1M HCl in appropriate volumes to remove any unreacted starting materials. The ethyl acetate layer was isolated and dried over sodium sulfate. The ethyl acetate was removed using a rotary evaporator to yield a brownish film on the sides of the flask. Hexanes were added to the flask and refluxed. A solid then formed on the sides of the flask, and the hexanes were removed via rotary evaporator to give 709.0 mg of 6 (81% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.537 (bs, 1H), δ 9.092 (t, J=5.6 Hz, 1H), δ 7.49 (dd, J=9.4 Hz, J=2.4 Hz 1H), δ (dd, J=8.8 Hz, J=2 Hz 1H), δ 7.268-7.228 (m, 2H), δ 6.91 (d, J=6.8 Hz, 2H), δ 6.82 (d, J=8.2 Hz, 1H), δ 4.48 (d, J=6 Hz, 2H), δ 3.729 (s, 3H).

後処理

  1. customTo a round bottom flask that has been
  2. customfire dried
  3. customflushed with a continuous stream of argon
  4. customequipped with a stir bean, DMF (4.8 ml)
  5. additionwas added
  6. extractionextracted 3× with saturated sodium bicarbonate, and 3× with 1M HCl in appropriate volumes
  7. customto remove
  8. customThe ethyl acetate layer was isolated
  9. dry with materialdried over sodium sulfate
  10. customThe ethyl acetate was removed
  11. customa rotary evaporator
  12. customto yield a brownish film on the sides of the flask
  13. temperaturerefluxed
  14. customA solid then formed on the sides of the flask
  15. customthe hexanes were removed via rotary evaporator

出典と根拠

ORDレコード
ord-3701ea7df8d64930a40c6c4e695d6822
出典データセット
uspto-grants-2010_08
特許番号
US07772216B2

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