Diethylamine → 1-(Cyclohexyl)methyl-3-{4-[(diethylamino)methyl]-[1,3]-oxazol-2-yl}-7-methoxy-1H-indole, hydrochloride salt

HRID 644060Notes

Reaction equation

HRID 644060 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)[O:6][CH:7]=1.[CH2:26]([NH:28][CH2:29][CH3:30])[CH3:27]>O1CCCC1.ClCCl>[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[O:6][CH:7]=[C:3]([CH2:2][N:28]([CH2:29][CH3:30])[CH2:26][CH3:27])[N:4]=3)=[CH:9]2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

5

Reactant 2

HCID 8021DiethylamineHCID 686996223-(4-chloromethyl-oxazol-2-yl)-1-cyclohexylmethyl-7-methoxy-1H-indole

Product 1

HCID 1317280721-(Cyclohexyl)methyl-3-{4-[(diethylamino)methyl]-[1,3]-oxazol-2-yl}-7-methoxy-1H-indole, hydrochloride saltYield 82.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4-chloromethyl-oxazol-2-yl)-1-cyclohexylmethyl-7-methoxy-1H-indole (100 mg, 0.28 mmol) in tetrahydrofuran (1 ml) was added diethylamine (0.29 ml, 2.8 mmol) and the reaction mixture subjected to microwave irradiation at 150° C. for 15 minutes. The reaction mixture was poured into a separating funnel, diluted with dichloromethane (40 ml) and washed with 5% aqueous sodium carbonate solution (2×25 ml), brine (20 ml), dried over magnesium sulfate and the solvent evaporated in vacuo to leave an orange oil. The oil was purified by flash column chromatography using 10% (v/v) methanol in dichloromethane to give the title compound (92 mg, 0.23 mmol) as the free base. The free base was dissolved in dichloromethane and hydrogen chloride (1M solution in diethyl ether; 2 ml, 2 mmol) was added. The mixture was concentrated in vacuo to afford the title compound as a 1:1 hydrochloride salt. 1H NMR (400 MHz, CD3OD): 0.97-1.28 (5H, m), 1.44 (6H, t, J 7.0), 1.5-1.8 (5H, m), 1.8-1.95 (1H, m), 3.3-3.5 (4H, m), 3.97 (3H, s), 4.29 (2H, d, J 7.0), 4.38 (2H, s), 6.8 (1H, d, J 8.0), 7.2 (1H, t, J 8.0), 7.8 (1H, s), 7.82 (1H, s), 8.2 (1H, s); EsIMS: m/z 396.0 [M+H]+, 323.4, 295.4, 268.3.

Workup

  1. customirradiation at 150° C. for 15 minutes
  2. additionThe reaction mixture was poured into a separating funnel
  3. washwashed with 5% aqueous sodium carbonate solution (2×25 ml), brine (20 ml)
  4. dry with materialdried over magnesium sulfate
  5. customthe solvent evaporated in vacuo
  6. customto leave an orange oil
  7. customThe oil was purified by flash column chromatography

Sources & evidence

ORD record
ord-314c452987374c7a9db9f355ddd50d43
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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