Triethylamine → 1-(4-Dimethylamino-4-phenylcyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methylethyl]thiourea

HRID 1394279Notes

Reaction equation

HRID 1394279 reaction equation
[CH3:1][CH:2]([CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)[NH2:3].C(N(CC)CC)C.[C:21](Cl)(Cl)=[S:22].[NH2:25][CH2:26][CH:27]1[CH2:32][CH2:31][C:30]([N:39]([CH3:41])[CH3:40])([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:29][CH2:28]1>C(Cl)(Cl)Cl>[CH3:40][N:39]([CH3:41])[C:30]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:31][CH2:32][CH:27]([CH2:26][NH:25][C:21]([NH:3][CH:2]([CH3:1])[CH2:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][CH:6]=2)=[S:22])[CH2:28][CH2:29]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9287(+-)-alpha-MethyltryptamineHCID 10040ThiophosgeneHCID 21082146(4-Aminomethyl-1-phenylcyclohexyl)dimethylamine

Product 1

HCID 596818901-(4-Dimethylamino-4-phenylcyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methylethyl]thiourea

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent3×

Conditions

Temperature
-5 °C

Procedure

α-methyltryptamine (261.4 mg, 1.5 mmole) was dissolved in dry chloroform (15 ml) and combined with triethylamine (422 μl, 3 mmole). The mixture was cooled to −5° C. Thiophosgene (115 μl, 1.5 mmole) dissolved in chloroform (10 ml) was then added dropwise, resulting in the formation of a precipitate. After a reaction time of 18 h at RT, (4-aminomethyl-1-phenyl-cyclohexyl)-dimethylamine (348.55 mg, 1.5 mmole) dissolved in chloroform (10 ml) was added. After 20 h stirring at RT, the reaction mixture was clear. Working up was performed by washing the batch with saturated NaHCO3 solution (3×5 ml) and water (5 ml). The organic phase was dried with Na2SO4 and evaporated. The product was a mixture of two diastereoisomers. These were purified and separated by column chromatography [silica gel 60 (70 g); eluent: MeOH/EE 1:5 (1500 ml)]. The more nonpolar diastereoisomer of 1-(4-dimethylamino-4-phenylcyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methyl-ethyl]thiourea (177 mg, m.p. 99-104° C., 26%) and also the more polar diastereoisomer of 1-(4-dimethylamino-4-phenylcyclohexylmethyl)-3-[2-(1H-indol-3-yl)-1-methylethyl]thiourea (152 mg, m.p. 93-95° C., 23%) were colorless solids.

Workup

  1. additionwas then added dropwise
  2. customresulting in the formation of a precipitate
  3. additionwas added
  4. washby washing the batch with saturated NaHCO3 solution (3×5 ml) and water (5 ml)
  5. dry with materialThe organic phase was dried with Na2SO4
  6. customevaporated
  7. additiona mixture of two diastereoisomers
  8. customThese were purified
  9. customseparated by column chromatography [silica gel 60 (70 g); eluent: MeOH/EE 1:5 (1500 ml)]

Sources & evidence

ORD record
ord-28a43240c4ae4c9fadae856ec45e6016
Source dataset
uspto-grants-2008_03
Patent number
US07348354B2

Reaction notes

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