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

HRID 1013133

반응식

HRID 1013133 반응식
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

참가 물질

8

반응물 6

HCID 8471Triethylamine2회HCID 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9dc07a04d76b43d6966bf0e5e02e85e4
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07981906B2

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