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

HRID 28479Notes

Reaction equation

HRID 28479 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14][C@H:13]([CH2:16]OS(C4C=CC(Br)=CC=4)(=O)=O)[O:12][C:8]3=2)[N:3]=1.[F:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][CH:33]=[C:32]2[CH2:38][CH:39]1[CH2:44][CH2:43][CH2:42][NH:41][CH2:40]1.C(N(CC)CC)C>CS(C)=O>[F:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][CH:33]=[C:32]2[CH2:38][CH:39]1[CH2:44][CH2:43][CH2:42][N:41]([CH2:16][CH:13]2[O:12][C:8]3=[C:9]4[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14]2)[N:3]=[C:2]([CH3:1])[CH:11]=[CH:10]4)[CH2:40]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 20624762[(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl4-bromobenzenesulfonateHCID 218920965-Fluoro-3-piperidin-3-ylmethyl-1h-indole

Product 1

HCID 100036512-[3-(5-Fluoro-1H-indol-3-ylmethyl)-piperidin-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-f]quinolin-2-ylmethyl ester (0.090 g, 0.24 mmol), 5-fluoro-3-piperidin-3-ylmethyl-1H-indole (0.56 g, 0.24 mmol) and triethylamine (0.042 mL, 0.36 mmol) in dimethylsulfoxide (10 mL) was heated at 90° C. under nitrogen overnight. The reaction mixture was quenched with 1N sodium hydroxide and extracted with methylene chloride (3×50 mL). The organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum. The crude oil was column chromatographed on silica gel (5% methanol-75% ethyl acetate-20% hexane). The product-containing fractions were concentrated in vacuum to give 0.048 g (53%) of the (S)-enantiomer of the title compound as a brown oil. The dihydrochloride salt was prepared in ethyl acetate and collected as 0.037 g of a yellow solid, m.p. 68° C. (dec).

Workup

  1. customThe reaction mixture was quenched with 1N sodium hydroxide
  2. extractionextracted with methylene chloride (3×50 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 (5% methanol-75% ethyl acetate-20% hexane)
  8. concentrationThe product-containing fractions were concentrated in vacuum

Sources & evidence

ORD record
ord-0f29994b53e64bf0a3364428b2dfd6ea
Source dataset
uspto-grants-2008_09
Patent number
US07419986B2

Reaction notes

Loading…