Dimethylformamide → N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodonicotinamide

HRID 1795823ノート

反応式

HRID 1795823 の反応式
S(Cl)(Cl)=O.[Cl:5][C:6]1[N:14]=[CH:13][CH:12]=[C:11]([I:15])[C:7]=1[C:8]([OH:10])=O.CN(C)C=O.[F:21][C:22]([F:40])([F:39])[C:23]1[CH:24]=[C:25]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[CH2:26][NH:27][CH2:28][CH2:29][CH2:30][OH:31]>O1CCCC1.O.C(N(CC)CC)C>[F:21][C:22]([F:39])([F:40])[C:23]1[CH:24]=[C:25]([CH:32]=[C:33]([C:35]([F:36])([F:38])[F:37])[CH:34]=1)[CH2:26][N:27]([CH2:28][CH2:29][CH2:30][OH:31])[C:8](=[O:10])[C:7]1[C:11]([I:15])=[CH:12][CH:13]=[N:14][C:6]=1[Cl:5]

参加物

8

反応物 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 116380193-(3,5-Bis(trifluoromethyl)benzylamino)propanolHCID 177501742-Chloro-4-iodonicotinic acid

生成物 1

HCID 11786369N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodonicotinamide収率 92%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8471Triethylamine溶媒

反応条件

温度
100 °C

実験手順

To thionyl chloride (20 mL), 2-chloro-4-iodonicotinic acid (8.40 g) were added along with N,N-dimethylformamide (3 droplets) and the mixture was stirred at 100° C. for 3 hours. The reaction mixture was then distilled under reduced pressure to obtain a yellow residue. 3-(3,5-bis(trifluoromethyl)benzylamino)propanol (10.7 g) and triethylamine (20.6 mL) were dissolved in tetrahydrofuran (150 mL). While the mixture was chilled on an ice bath, a tetrahydrofuran solution of the yellow residue (50 mL) was added. After stirred for 1 hour, the mixture was further stirred for additional two hours at room temperature. Subsequently, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was then dried on anhydrous sodium sulfate. Following the removal of the solvent, the remaining residue was purified on a silica gel column chromatography (ethyl acetate:n-hexane=3:1) to obtain N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodonicotinamide (15.4 g, 92%).

後処理

  1. distillationThe reaction mixture was then distilled under reduced pressure
  2. customto obtain a yellow residue
  3. temperatureWhile the mixture was chilled on an ice bath
  4. stirringAfter stirred for 1 hour
  5. stirringthe mixture was further stirred for additional two hours at room temperature
  6. extractionthe mixture was extracted with ethyl acetate
  7. dry with materialThe extract was then dried on anhydrous sodium sulfate
  8. customthe removal of the solvent
  9. customthe remaining residue was purified on a silica gel column chromatography (ethyl acetate:n-hexane=3:1)

出典と根拠

ORDレコード
ord-13abe883f4b346bf8536000001b197bc
出典データセット
uspto-grants-2006_04
特許番号
US07030107B2

反応ノート

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