Triethylamine → 3-(1-Methyl-indol-3-yl)-4-{1-[1-{2,2,2-trifluoro-ethyl)-piperidin-4-yl]-indol-3-yl}-1H-pyrrole-2,5-dione

HRID 1077950노트

반응식

HRID 1077950 반응식
[F:1][C:2]([F:20])([F:19])[CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)[CH2:6][CH2:5]1.[C:21](Cl)(=[O:25])[C:22](Cl)=O.Cl.[C:28](=[NH:31])([OH:30])[CH3:29].[CH2:32]([N:34]([CH2:37][CH3:38])[CH2:35][CH3:36])C.O.[C:40]1(C)[CH:45]=CC(S(O)(=O)=O)=[CH:42][CH:41]=1>CCOCC>[CH3:32][N:34]1[C:37]2[C:38](=[CH:45][CH:40]=[CH:41][CH:42]=2)[C:36]([C:29]2[C:28](=[O:30])[NH:31][C:21](=[O:25])[C:22]=2[C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]([CH:7]3[CH2:8][CH2:9][N:4]([CH2:3][C:2]([F:1])([F:19])[F:20])[CH2:5][CH2:6]3)[CH:11]=2)=[CH:35]1

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 65578Oxalyl chloride2회HCID 521998p-Toluenesulfonic acid monohydrateHCID 229072831-[1-(2,2,2-Trifluoroethyl)-piperidin-4-yl]-indoleHCID 178465697HCID 178465697, 화합물

생성물 1

HCID 229072483-(1-Methyl-indol-3-yl)-4-{1-[1-{2,2,2-trifluoro-ethyl)-piperidin-4-yl]-indol-3-yl}-1H-pyrrole-2,5-dione수율 30.8%

시약·촉매·용매 1

HCID 3283Diethyl Ether용매

실험 절차

To a stirred 0° C. solution of 1-[1-(2,2,2-trifluoro-ethyl)-piperidin-4-yl]-indole (180 mg, 0.64 mmol) in dry ether (3 mL ) was added oxalyl chloride (0.06 mL, 0.7 mmol). The reaction mixture was warmed to ambient temperature for 30 minutes. An additional amount of oxalyl chloride (0.04 mL, 0.5 mmol ) was added. After 30 minutes, a yellow precipitate formed which was filtered with the exclusion of moisture and air, and washed with a small amount of ether. The collected precipitant was dissolved in dry methylene chloride (10 mL) and treated with isopropyl(1-methyl) indol-3-yl)acetimidate hydrochloride (190 mg, 0.71 mmol ) followed by slow addition of triethylamine (0.44 mL, 3.2 mmol) at 0° C. After 4 hours at ambient temperature, p-toluene sulfonic acid monohydrate (0.61 g, 3.2 mmol) was added. After 30 minutes the mixture was quenched with saturated aqueous sodium hydrogen carbonate solution (40 mL). The organic phase was separated, washed with water, dried, and evaporated. The residue was recrystallized from hot dioxane and yielded 100 mg of bright orange crystals. Recrystallization of the mother liquor from THF yielded a second crop (60 mg). Yield: 160 mg of bright orange crystals (49% of theory) M.Pt.: >250° C.

후처리

  1. customa yellow precipitate formed which
  2. filtrationwas filtered with the exclusion of moisture and air
  3. washwashed with a small amount of ether
  4. dissolutionThe collected precipitant was dissolved in dry methylene chloride (10 mL)
  5. waitAfter 4 hours at ambient temperature
  6. customAfter 30 minutes the mixture was quenched with saturated aqueous sodium hydrogen carbonate solution (40 mL)
  7. customThe organic phase was separated
  8. washwashed with water
  9. customdried
  10. customevaporated
  11. customThe residue was recrystallized from hot dioxane

출처 및 근거

ORD 기록
ord-3a76e7e19651415b896ca240cdbbacba
출처 데이터셋
uspto-grants-1996_08
특허 번호
US05545636

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