Diethyl Ether → 1-(4-dimethylamino-4-phenyl-cyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methyl-ethyl]-urea

HRID 1394267Notes

Reaction equation

HRID 1394267 reaction equation
[CH3:1][N:2]([CH3:32])[C:3]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:11]([NH:13][CH:14]([CH3:25])[CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)=[O:12])[CH2:5][CH2:4]1.[Cl:33][Si](C)(C)C.C(OCC)C>CC(CC)=O>[ClH:33].[CH3:32][N:2]([CH3:1])[C:3]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:11]([NH:13][CH:14]([CH3:25])[CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)=[O:12])[CH2:5][CH2:4]1.[CH3:32][N:2]([CH3:1])[C:3]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:11]([NH:13][CH:14]([CH3:25])[CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)=[O:12])[CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 6397ChlorotrimethylsilaneHCID 117544171-(4-dimethylamino-4-phenyl-cyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methyl-ethyl]-urea

Product 2

HCID 117544161-(4-Dimethylamino-4-phenylcyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methylethyl]urea hydrochlorideHCID 117544171-(4-dimethylamino-4-phenyl-cyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methyl-ethyl]-ureaYield 202.5%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

The more polar diastereoisomer of 1-(4-dimethylamino-4-phenyl-cyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methyl-ethyl]-urea (219 mg, 0.5 mmole) was dissolved in ethyl methyl ketone (40 ml). Chlorotrimethylsilane (95 μl, 0.75 mmole) was added dropwise with stirring at RT. After one hour's stirring at RT, no precipitate had formed. The reaction solution was reduced to 5 ml under a vacuum and combined with diethyl ether (15 ml). The mixture was then vigorously stirred at RT for 1 h. An almost colorless precipitate was formed. The solid was filtered out, washed with diethyl ether (3×3 ml) and dried under a vacuum. The hydrochloride of the more polar diastereoisomer of 1-(4-dimethylamino-4-phenyl-cyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methyl-ethyl]-urea (219 mg, m.p. 170-174° C., 93%; Example 26) was obtained in this manner as a colorless solid.

Workup

  1. stirringAfter one hour's stirring at RT
  2. customno precipitate had formed
  3. stirringThe mixture was then vigorously stirred at RT for 1 h
  4. customAn almost colorless precipitate was formed
  5. filtrationThe solid was filtered out
  6. washwashed with diethyl ether (3×3 ml)
  7. customdried under a vacuum

Sources & evidence

ORD record
ord-eaffb8e3aff844fea41f90f597079ed1
Source dataset
uspto-grants-2008_03
Patent number
US07348354B2

Reaction notes

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