Triphenylphosphine → n-Tert-butyl-1-cyano-n-methyl-1-[(r)-3-(1-methyl-2-pyrrolidinylmethyl)-1-tosyl-1h-indol-5-yl]methanesulfonamide

HRID 651713Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 651713
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[BH4-].[Na+].[C:22]([N:26]([CH3:33])[S:27]([CH2:30][C:31]#[N:32])(=[O:29])=[O:28])([CH3:25])([CH3:24])[CH3:23].[H-].[Na+].Br[C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[N:42]([S:46]([C:49]1[CH:55]=[CH:54][C:52]([CH3:53])=[CH:51][CH:50]=1)(=[O:48])=[O:47])[CH:41]=[C:40]2[CH2:56][C@H:57]1[CH2:61][CH2:60][CH2:59][N:58]1[CH3:62]>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[C:22]([N:26]([CH3:33])[S:27]([CH:30]([C:31]#[N:32])[C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[N:42]([S:46]([C:49]1[CH:55]=[CH:54][C:52]([CH3:53])=[CH:51][CH:50]=1)(=[O:47])=[O:48])[CH:41]=[C:40]2[CH2:56][C@H:57]1[CH2:61][CH2:60][CH2:59][N:58]1[CH3:62])(=[O:28])=[O:29])([CH3:25])([CH3:24])[CH3:23]

Komponenten

9

Edukt 5

HCID 11776TriphenylphosphineHCID 24758Sodium hydrideHCID 4311764Sodium borohydrideHCID 21709114N-tert-butyl-1-cyano-N-methylmethanesulfonamideHCID 54296311(R)-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1-tosyl-1H-indole

Produkt 1

HCID 53762173n-Tert-butyl-1-cyano-n-methyl-1-[(r)-3-(1-methyl-2-pyrrolidinylmethyl)-1-tosyl-1h-indol-5-yl]methanesulfonamideAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

To a stirred suspension of dichlorobis(triphenylphosphine)palladium (II) (704 mg, 1 mmol) and triphenylphosphine (525 mg, 2 mmol) in ethyleneglycol dimethylether (5 ml) at ambient temperature under an atmosphere of nitrogen was added sodium borohydride (38 mg, 1 mmol) in one portion. The green slurry was stirred for 5 min, then N-tert-butyl-cyano-N-methylmethanesulfonamide (from step (c), 1.04 g, 5.4 mmol) was added in one portion. The green slurry was then cooled to 0-5° C. and sodium hydride (60% dispersion in mineral oil) (441 mg, 11 mmol) was added portionwise, maintaining the temperature below 5° C. The brown solution was then warmed to ambient temperature over a 10 min period, before a solution of (R)-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1-tosyl-1H-indole (from step (d), 2.24 g, 5 mmol) in ethyleneglycol dimethyl ether (15 ml) was added dropwise. The brown slurry was then warmed to reflux. Reflux was maintained for 1.5 hr after which time the dark brown solution was cooled to ambient temperature. The reaction mixture was then poured into water (20 ml) and extracted with ethyl acetate (3×25 ml). The organic extracts were combined and evaporated in vacuo to yield a brown oil. This was purified by flash column chromatography (ethyl acetate:hexane:diethylamine 1:1:0.1 as eluant) to yield the subtitle compound (1.23 g, 45%) as a golden oil.

Aufarbeitung

  1. temperaturemaintaining the temperature below 5° C
  2. additionwas added dropwise
  3. temperatureThe brown slurry was then warmed to reflux
  4. temperatureReflux
  5. temperaturewas maintained for 1.5 hr after which time the dark brown solution
  6. temperaturewas cooled to ambient temperature
  7. extractionextracted with ethyl acetate (3×25 ml)
  8. customevaporated in vacuo
  9. customto yield a brown oil
  10. customThis was purified by flash column chromatography (ethyl acetate:hexane:diethylamine 1:1:0.1 as eluant)

Quellen und Nachweise

ORD-Eintrag
ord-a5a63d26e1d640fcbcc119f9b33a24a1
Quelldatensatz
uspto-grants-2001_08
Patentnummer
US06281357B1

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