Triethylamine → 2-[3-(5-Fluoro-1h-indol-3-ylmethyl)-azetidin-1-ylmethyl]-8-methyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinoline

HRID 720386Notes

Reaction equation

HRID 720386 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][C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[C:39]([F:42])[CH:40]=3)[NH: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:37][CH:38]=1)[NH:35][CH:34]=[C:33]2[CH2:32][CH:30]1[CH2:31][N:28]([CH2:16][CH:14]2[O:15][C:6]3=[C:5]4[C:46](=[CH:47][CH:8]=[C:7]3[O:12][CH2:13]2)[N:45]=[C:48]([CH3:49])[CH:9]=[CH:10]4)[CH2:29]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 692040353-Azetidin-3-ylmethyl-5-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 99317802-[3-(5-Fluoro-1h-indol-3-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 (0.35 g, 0.80 mmol), 3-azetidin-3-ylmethyl-5-fluoro-1H-indole (0.19 g, 0.96 mmol) and triethylamine (0.16 mL, 1.2 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 concentrated in vacuum. The resulting crude oil was column chromatographed on silica gel (3% methanol-ethyl acetate). The product-containing fractions were concentrated in vacuum to give 0.090 g of the (S)-enantiomer of the title compound as a brown oil. The dihydrochloride salt was prepared in ethyl acetate and collected as 0.068 g of a yellow solid, m.p. 125° 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. concentrationconcentrated in vacuum
  7. customchromatographed on silica gel (3% methanol-ethyl acetate)
  8. concentrationThe product-containing fractions were concentrated in vacuum

Sources & evidence

ORD record
ord-c2734978d6454ce7b5f180e617e67890
Source dataset
uspto-grants-2006_11
Patent number
US07135479B2

Reaction notes

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