1,4-Dioxane → 1-(Cyclohexyl)methyl-7-methoxy-3-(4-{[N-(2-methoxyethyl)-N-methylamino]methyl}-[1,3]-thiazol-2-yl)-1H-indole, hydrochloride salt

HRID 644038Notes

Reaction equation

HRID 644038 reaction equation
[Cl:1][CH2:2][C:3]1[N:4]=[C:5]([C:8]2[C:16]3[C:11](=[C:12]([O:17][CH3:18])[CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:19][CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[CH:9]=2)[S:6][CH:7]=1.[CH3:26][O:27][CH2:28][CH2:29][NH:30][CH3:31].O1CCOCC1>C(#N)C>[ClH:1].[CH:20]1([CH2:19][N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[C:8]([C:5]3[S:6][CH:7]=[C:3]([CH2:2][N:30]([CH2:29][CH2:28][O:27][CH3:26])[CH3:31])[N:4]=3)=[CH:9]2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 300977(2-Methoxyethyl)(methyl)amineHCID 68697908HCID 68697908, compound

Product 1

HCID 1317280691-(Cyclohexyl)methyl-7-methoxy-3-(4-{[N-(2-methoxyethyl)-N-methylamino]methyl}-[1,3]-thiazol-2-yl)-1H-indole, hydrochloride salt

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-[4-(chloromethyl)thiazol-2-yl]-1-(cyclohexyl)methyl-7-methoxy-1H-indole (100 mg, 0.27 mmol), (2-methoxyethyl)methylamine (119 mg, 1.33 mmol), 1,4-dioxane (2 ml), and acetonitrile (1 ml) was subjected to microwave irradiation for 10 min at 160° C. The reaction mixture was concentrated in vacuo and the obtained reside was mixed with aqueous sodium hydroxide (1M; 50 ml) and extracted with dichloromethane (4×50 ml). The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The obtained residue was purified by column chromatography eluting with ethyl acetate to give the free base of the title compound as an oil. Hydrochloride salt formation was achieved by the addition of hydrogen chloride (1M solution in diethyl ether; 3 ml) to a solution of the free base in diethyl ether (15 ml). The mixture was concentrated in vacuo to afford the title compound as a 1:1 hydrochloride salt (95.1 mg). 1H NMR (400 MHz, CD3OD) δ 1.00-1.30 (5H, m), 1.55-1.94 (6H, m), 3.00 (3H, s), 3.32-3.66 (5H, m), 3.80 (2H, t, J 5.0), 3.97 (3H, s), 4.29 (2H, d, J 7.2), 4.52 (2H, s), 6.81 (1H, d, J 8.0), 7.16 (1H, dd, J 8.0, 8.0), 7.62 (1H, s), 7.80 (1H, d, J 8.0), 7.85 (1H, s).

Workup

  1. customirradiation for 10 min at 160° C
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additionthe obtained reside was mixed with aqueous sodium hydroxide (1M; 50 ml)
  4. extractionextracted with dichloromethane (4×50 ml)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe obtained residue was purified by column chromatography
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-b5126ebf9f85405abd50afe0b4e0ce22
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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