Diisopropylethylamine → 1-{[1-(Cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-2,3,5,6-tetramethylpiperazine, hydrochloride salt

HRID 968642Notes

Reaction equation

HRID 968642 reaction equation
C(N(C(C)C)CC)(C)C.[CH3:10][CH:11]1[CH:16]([CH3:17])[NH:15][CH:14]([CH3:18])[CH:13]([CH3:19])[NH:12]1.[CH:20]1([CH2:26][N:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][C:34]=3[O:36][CH3:37])[C:29]([C:38]([Cl:40])=[O:39])=[CH:28]2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>ClCCl>[ClH:40].[CH:20]1([CH2:26][N:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][C:34]=3[O:36][CH3:37])[C:29]([C:38]([N:12]3[CH:13]([CH3:19])[CH:14]([CH3:18])[NH:15][CH:16]([CH3:17])[CH:11]3[CH3:10])=[O:39])=[CH:28]2)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5219702,3,5,6-TetramethylpiperazineHCID 859058491-(Cyclohexylmethyl)-7-methoxyindole-3-carbonyl chloride

Product 1

HCID 1317267001-{[1-(Cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-2,3,5,6-tetramethylpiperazine, hydrochloride salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of diisopropylethylamine (0.83 ml, 4.90 mmol) and 2,3,5,6-tetramethylpiperazine (0.35 g, 2.45 mmol) in dichloromethane (5 ml) was added a solution of 1-(cyclohexylmethyl)-7-methoxyindole-3-carbonyl chloride (0.33 g, 1.08 mmol, prepared following the method in Example 1) in dichloromethane (5 ml). The mixture was stirred at room temperature for 6 h, evaporated under reduced pressure and the residue purified by flash chromatography eluting with 5-10% (v/v) methanol in dichloromethane to afford the title compound (free base) as a colourless oil (0.43 g). The free base (0.1 g, 0.24 mmol) was dissolved in dichloromethane (1 ml), treated dropwise with 2 M hydrochloric acid in diethyl ether (0.3 ml) and diethyl ether (3 ml). The resulting precipitate was collected by filtration, washed with diethyl ether (15 ml) and dried under reduced pressure to afford the title compound (1:1 hydrochloric acid salt) as a white solid (0.09 g, 0.20 mmol). 1H NMR (400 MHz, CD3OD) δH 0.98-1.39 (8H, m), 1.42 (6H, d, J 7.0), 1.64-1.89 (9H, m), 3.44-3.70 (3H, m), 3.95 (3H, s), 4.21-4.34 (3H, m), 6.77 (1H, d, J 7.7), 7.11 (1H, t, J 8.2), 7.38 (1H, d, J 8.2), 7.58 (1H, s); EIMS: m/z 412.4 [M+H]+.

Workup

  1. customprepared
  2. customevaporated under reduced pressure
  3. customthe residue purified by flash chromatography
  4. washeluting with 5-10% (v/v) methanol in dichloromethane

Sources & evidence

ORD record
ord-3dfec5ecbcd7415ca2ff893b607327d7
Source dataset
uspto-grants-2007_12
Patent number
US07304064B2

Reaction notes

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