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 1260346노트

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HRID 1260346 반응식
[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

참가 물질

7

반응물 4

HCID 31268Pyrrolidine2회HCID 81531DiisopropylethylamineHCID 19083224Phosgen tolueneHCID 866191675-Methylene-3-(2,2,3,3-tetrafluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)thiazolidin-2-imine

생성물 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

시약·촉매·용매 2

HCID 6344Dichloromethane용매2회HCID 14923Ammonium Hydroxide용매

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온도
-20 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-da230375787f429f9ad57c48890acbb9
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08470813B2

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