Triethylamine → 2-[3-(6-Fluoro-indol-1-ylmethyl)-azetidin-1-ylmethyl]-8-methyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinoline

HRID 720392Notes

Reaction equation

HRID 720392 reaction equation
CC1C=N[C:5]2[C:6]3[O:15][C@@H:14]([CH2:16]OS(C4C=CC(Br)=CC=4)(=O)=O)[CH2:13][O:12][C:7]=3[CH:8]=[CH:9][C:10]=2C=1.[NH:28]1[CH2:31][CH:30]([CH2:32][N:33]2[C:41]3[C:36](=[CH:37][CH:38]=[C:39]([F:42])[CH:40]=3)[CH:35]=[CH:34]2)[CH2:29]1.C([N:45]([CH2:48][CH3:49])[CH2:46][CH3:47])C>CS(C)=O>[F:42][C:39]1[CH:40]=[C:41]2[C:36]([CH:35]=[CH:34][N:33]2[CH2:32][CH:30]2[CH2:31][N:28]([CH2:16][CH:14]3[O:15][C:6]4=[C:5]5[C:46](=[CH:47][CH:8]=[C:7]4[O:12][CH2:13]3)[N:45]=[C:48]([CH3:49])[CH:9]=[CH:10]5)[CH2:29]2)=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 218920951-Azetidin-3-ylmethyl-6-fluoro-1H-indoleHCID 131726053(2R)-4-bromobenzenesulfonic acid 8-methyl-2,3-dihydro-[1,4]dioxino[2,3-]quinolin-2-ylmethyl ester

Product 1

HCID 104097202-[3-(6-Fluoro-indol-1-ylmethyl)-azetidin-1-ylmethyl]-8-methyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinoline

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (2R)-4-bromobenzenesulfonic acid 8-methyl-2,3-dihydro-[1,4]dioxino[2,3-]quinolin-2-ylmethyl ester (0.4 g, 0.93 mmol), 1-azetidin-3-ylmethyl-6-fluoro-1H-indole (0.19 g, 0.93 mmol) and triethylamine (0.19 ml, 1.4 mmol) in dimethylsulfoxide (20 ml) was heated at 90° C. under nitrogen overnight. The reaction mixture was quenched with 1N sodium hydroxide and extracted with methylene chloride (3×80 mL). The organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum. The crude oil was column chromatographed on silica gel (3% methanol-ethyl acetate). The product-containing fractions were concentrated in vacuum to give 0.1 g of the (S)-enantiomer of the title compound as a brown oil. The hydrogen chloride salt was prepared in ethyl acetate and collected as a yellow solid: mp: 138° C. (dec).

Workup

  1. customThe reaction mixture was quenched with 1N sodium hydroxide
  2. extractionextracted with methylene chloride (3×80 mL)
  3. washThe organic layer was washed with water (3×50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed under vacuum
  7. customchromatographed on silica gel (3% methanol-ethyl acetate)
  8. concentrationThe product-containing fractions were concentrated in vacuum

Sources & evidence

ORD record
ord-181f101b611347c683a64b245433bb43
Source dataset
uspto-grants-2006_11
Patent number
US07135479B2

Reaction notes

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