Sodium Hydroxide → N-[(cis)-3-(5-fluoro-1H-indol-3-yl)cyclopentyl]-N-{[(2S)-8-methoxy-2,3-dihydro-1,4-benzodioxin-2-yl]methyl}amine

HRID 1824010Notes

Reaction equation

HRID 1824010 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([O:23][CH3:24])=[CH:20][CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[F:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][CH:30]=[C:29]2[C@@H:35]1[CH2:39][CH2:38][C@H:37]([NH2:40])[CH2:36]1.[OH-].[Na+]>CS(C)=O>[F:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][CH:30]=[C:29]2[C@@H:35]1[CH2:39][CH2:38][C@H:37]([NH:40][CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([O:23][CH3:24])=[CH:20][CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)[CH2:36]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 11792133[(2R)-8-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-yl]methyl 4-methylbenzenesulfonateHCID 68827169cis-3-(5-Fluoro-1H-indol-3-yl)-cyclopentylamine

Product 1

HCID 10023651N-[(cis)-3-(5-fluoro-1H-indol-3-yl)cyclopentyl]-N-{[(2S)-8-methoxy-2,3-dihydro-1,4-benzodioxin-2-yl]methyl}amineYield 48%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of [(2R)-8-methoxy-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzene-sulfonate (0.5 g, 1.42 mmole) and cis-3-(5-fluoro-1H-indol-3-yl)-cyclopentyl-amine (0.24 g, 1.1 mmol) in anhydrous DMSO (10 mL) was heated at 80° C. for 30 h. The cooled reaction mixture was poured into 1 N aqueous NaOH (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), then were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give 0.5 g of crude product. Flash chromatography on silica gel (10% MeOH/ethyl acetate) afforded 0.2 g (48%) of the title compound as a thick oil, which was converted to its hydrochloride salt (0.195 g): MS (ESI) m/z 397 [M+H]+.

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layers were washed with water (50 mL) and brine (50 mL)
  4. dry with materialwere dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give 0.5 g of crude product

Sources & evidence

ORD record
ord-b7de644fc0da48e5973bdb107cbfc545
Source dataset
uspto-grants-2006_05
Patent number
US07041697B2

Reaction notes

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