Triethylamine → N-(2-(Pyridin-3-ylmethyl)quinuclidin-3-yl)benzofuran-2-carboxamide

HRID 82425

Reaktionsgleichung

Reaktionsgleichung von HRID 82425
C1(OP(Cl)(OC2C=CC=CC=2)=O)C=CC=CC=1.[O:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[CH:20]=[C:19]1[C:27]([OH:29])=O.C(N(CC)CC)C.[NH2:37][C@H:38]1[CH:43]2[CH2:44][CH2:45][N:40]([CH2:41][CH2:42]2)[C@@H:39]1[CH2:46][C:47]1[CH:48]=[N:49][CH:50]=[CH:51][CH:52]=1.C1(C)C=CC(C([C@@](C(O)=O)(O)[C@@](C(C2C=CC(C)=CC=2)=O)(O)C(O)=O)=O)=CC=1.[OH-].[Na+]>ClCCl>[N:49]1[CH:50]=[CH:51][CH:52]=[C:47]([CH2:46][CH:39]2[CH:38]([NH:37][C:27]([C:19]3[O:18][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=4[CH:20]=3)=[O:29])[CH:43]3[CH2:42][CH2:41][N:40]2[CH2:45][CH2:44]3)[CH:48]=1

Komponenten

8

Edukt 6

HCID 8471Triethylamine2×HCID 10331Benzofuran-2-carboxylic acidHCID 14798Sodium HydroxideHCID 75654Diphenyl chlorophosphateHCID 29414711Di-para-toluoyl-L-tartaric acidHCID 66669685(2R,3S)-3-amino-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane

Produkt 1

HCID 22311391N-(2-(Pyridin-3-ylmethyl)quinuclidin-3-yl)benzofuran-2-carboxamideAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Diphenylchlorophosphate (96 μL, 124 mg, 0.46 mmol) was added drop-wise to a solution of the benzofuran-2-carboxylic acid (75 mg, 0.46 mmol) and triethylamine (64 μL, 46 mg, 0.46 mmol) in dry dichloromethane (1 mL). After stirring at ambient temperature for 45 min, a solution of (2R,3S)-3-amino-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane (0.10 g, 0.46 mmol) (that derived from the di-p-toluoyl-L-tartaric acid salt) and triethylamine (64 μL, 46 mg, 0.46 mmol) in dry dichloromethane (1 mL) was added. The reaction mixture was stirred overnight at ambient temperature, and then treated with 10% sodium hydroxide (1 mL). The biphasic mixture was separated, and the organic layer and a chloroform extract (2 mL) of the aqueous layer was concentrated by rotary evaporation. The residue was dissolved in methanol and purified by HPLC on a C18 silica gel column, using an acetonitrile/water gradient, containing 0.05% trifluoroacetic acid, as eluent. Concentration of selected fractions, partitioning of the resulting residue between chloroform and saturated aqueous sodium bicarbonate, and evaporation of the chloroform gave 82.5 mg (50% yield) of a white powder. The NMR spectrum was identical to that obtained for the 2S,3R isomer.

Aufarbeitung

  1. additionwas added
  2. stirringThe reaction mixture was stirred overnight at ambient temperature
  3. customThe biphasic mixture was separated
  4. extractionthe organic layer and a chloroform extract (2 mL) of the aqueous layer
  5. concentrationwas concentrated by rotary evaporation
  6. dissolutionThe residue was dissolved in methanol
  7. custompurified by HPLC on a C18 silica gel column
  8. additioncontaining 0.05% trifluoroacetic acid
  9. customConcentration of selected fractions, partitioning of the resulting residue between chloroform and saturated aqueous sodium bicarbonate, and evaporation of the chloroform

Quellen und Nachweise

ORD-Eintrag
ord-42d0b9371d894374aa4383ac993a65ef
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846715B2

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