Sodium Chloride → (R)-2-chloro-N-[1-[(3-chloro-2-thienyl)methyl]propyl]-3-nitro-4-pyridinamine

HRID 1857040ノート

反応式

HRID 1857040 の反応式
[Cl:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[CH2:7][C@H:8]([NH:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14](O)[C:13]=1[N+:19]([O-:21])=[O:20])[CH2:9][CH3:10].CCN(C(C)C)C(C)C.Cl.P(Cl)(Cl)([Cl:34])=O.[Cl-].[Na+]>C1(C)C=CC=CC=1>[Cl:34][C:14]1[C:13]([N+:19]([O-:21])=[O:20])=[C:12]([NH:11][C@@H:8]([CH2:7][C:3]2[S:4][CH:5]=[CH:6][C:2]=2[Cl:1])[CH2:9][CH3:10])[CH:17]=[CH:16][N:15]=1

参加物

6

反応物 4

HCID 5234Sodium ChlorideHCID 24813Phosphorus oxychlorideHCID 10997398Ethylbis(propan-2-yl)amine hydrochlorideHCID 178455879HCID 178455879、化合物2 回

生成物 1

HCID 10882512(R)-2-chloro-N-[1-[(3-chloro-2-thienyl)methyl]propyl]-3-nitro-4-pyridinamine

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
60 °C

実験手順

A toluene solution of (R)-N-[1-[(3-chloro-2-thienyl)methyl]propyl]-2-hydroxy-3-nitro-4-pyridinamine (Compound IV) (0.1 mole in 100 mL of toluene) containing 2 equivalents of DIPEA hydrochloride is heated to 60° C. and 20.6 grams of phosphorus oxychloride is added over 10 minutes with stirring. The reaction is stirred at 60° C. until complete (3 hours). After cooling to 0° C., 245 grams of 2N sodium chloride is added at such a rate so as to maintain the reaction temperature below 10° C. The biphasic mixture is stirred 1-2 hours at 0° C. before it is allowed to warm to room temperature overnight. The bottom aqueous layer is separated from the organic layer. The organic layer is concentrated in vacuo and the residue purified by flash chromatography eluting with 25.75 ethyl acetate:heptane to give Compound V. MS (EI) m/z 345 (10%). 1HNMR (500 Mhz, CDCl3 /CD3OD)δ1.0 (2H, t); 1.5-1.8 (2H, m); 2.9-3.2 (2H, m); 3.8 (1H, m); 6.5 (1H, bd); 6.6 (1H, d); 7.15 (1H, d); 7.9 (1H, d).

後処理

  1. stirringThe reaction is stirred at 60° C. until complete (3 hours)
  2. temperatureAfter cooling to 0° C.
  3. temperatureto maintain the reaction temperature below 10° C
  4. stirringThe biphasic mixture is stirred 1-2 hours at 0° C. before it
  5. temperatureto warm to room temperature overnight
  6. customThe bottom aqueous layer is separated from the organic layer
  7. concentrationThe organic layer is concentrated in vacuo
  8. customthe residue purified by flash chromatography
  9. washeluting with 25.75 ethyl acetate

出典と根拠

ORDレコード
ord-afeab450efc74d08be4464bf402da155
出典データセット
uspto-grants-2000_11
特許番号
US06143894

反応ノート

読み込み中…