Pyrrolidine → (NZ)-N-[5-methyl-3-(2,2,3,3-tetrafluoro-1,4-benzodioxin-6-yl)-1,3-thiazol-2-ylidene]pyrrolidine-1-carboxamide

HRID 1260346ノート

反応式

HRID 1260346 の反応式
[CH2:1]=[C:2]1[S:6][C:5](=[NH:7])[N:4]([C:8]2[CH:21]=[CH:20][C:11]3[O:12][C:13]([F:19])([F:18])[C:14]([F:17])([F:16])[O:15][C:10]=3[CH:9]=2)[CH2:3]1.[C:22](Cl)(Cl)=[O:23].C1(C)C=CC=CC=1.[CH:33]([N:36]([CH:39]([CH3:41])C)CC)([CH3:35])C.N1CCCC1>C(Cl)Cl.[NH4+].[OH-]>[CH3:1][C:2]1[S:6]/[C:5](=[N:7]\[C:22]([N:36]2[CH2:33][CH2:35][CH2:41][CH2:39]2)=[O:23])/[N:4]([C:8]2[CH:21]=[CH:20][C:11]3[O:12][C:13]([F:19])([F:18])[C:14]([F:16])([F:17])[O:15][C:10]=3[CH:9]=2)[CH:3]=1

参加物

7

反応物 4

HCID 31268Pyrrolidine2 回HCID 81531DiisopropylethylamineHCID 19083224Phosgen tolueneHCID 866191675-Methylene-3-(2,2,3,3-tetrafluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)thiazolidin-2-imine

生成物 1

HCID 24852961(NZ)-N-[5-methyl-3-(2,2,3,3-tetrafluoro-1,4-benzodioxin-6-yl)-1,3-thiazol-2-ylidene]pyrrolidine-1-carboxamide

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 14923Ammonium Hydroxide溶媒

反応条件

温度
-20 °C

実験手順

A solution of Example 22C (290 mg, 0.90 mmol) in CH2Cl2 (4.0 mL, 0.2 M) was added dropwise over 17 minutes to a −78° C. solution of 20% phosgene/toluene (630 μL, 1.2 mmol) in CH2Cl2 (5.0 mL, 0.2M). The mixture was stirred cold for 10 minutes after which diisopropylethylamine (140 μL, 0.80 mmol) was added dropwise over 3 minutes. The mixture was stirred cold for 45 minutes and allowed to warm to −20° C. over 1 hour; then allowed to warm to ambient temperature. After 1 hour at ambient temperature, pyrrolidine (135 μL, 1.6 mmol) was added and the mixture was stirred for 16 hours. To the solution was added more pyrrolidine (90 μL, 1.1 mmol), the mixture was stirred for 20 minutes, diluted with concentrated aqueous NH4OH (2 mL) and stirred for 5 minutes. The aqueous phase was separated and extracted with CH2Cl2 (3×). The combined organic phases were dried with Na2SO4, concentrated under reduced pressure, and chromatographed on Alltech silica eluting with 0-10% Et2O in 1:1 CH2Cl2/hexanes to provide the titled compound. 1H NMR (CD2Cl2) δ ppm 1.83 (m, 4H), 2.24 (d, 3H), 3.36 (m, 2H), 3.40 (m, 2H), 6.66 (d, 1 H), 7.25 (d, 1 H), 7.42 (dd, 1H), 7.54 (d, 1H); MS (ESI) 418 (M+H).

後処理

  1. additionwas added dropwise over 3 minutes
  2. temperatureto warm to ambient temperature
  3. waitAfter 1 hour at ambient temperature
  4. stirringthe mixture was stirred for 16 hours
  5. stirringthe mixture was stirred for 20 minutes
  6. stirringstirred for 5 minutes
  7. customThe aqueous phase was separated
  8. extractionextracted with CH2Cl2 (3×)
  9. dry with materialThe combined organic phases were dried with Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customchromatographed on Alltech silica eluting with 0-10% Et2O in 1:1 CH2Cl2/hexanes

出典と根拠

ORDレコード
ord-da230375787f429f9ad57c48890acbb9
出典データセット
uspto-grants-2013_06
特許番号
US08470813B2

反応ノート

読み込み中…