Triethylamine → HCID 10009810, compound

HRID 1394282Notes

Reaction equation

HRID 1394282 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:17])[C@H:5]([CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)[NH2:6].C(N(CC)CC)C.[C:25](Cl)(Cl)=[S:26].[NH2:29][CH2:30][CH:31]1[CH2:36][CH2:35][C:34]([N:43]([CH3:45])[CH3:44])([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:33][CH2:32]1>C(Cl)(Cl)Cl>[CH3:2][O:3][C:4](=[O:17])[CH:5]([NH:6][C:25]([NH:29][CH2:30][CH:31]1[CH2:32][CH2:33][C:34]([N:43]([CH3:45])[CH3:44])([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:35][CH2:36]1)=[S:26])[CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10040ThiophosgeneHCID 2734891Methyl tryptophanate hydrochlorideHCID 21082146(4-Aminomethyl-1-phenylcyclohexyl)dimethylamine

Product 1

HCID 10009810HCID 10009810, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent3×

Conditions

Temperature
-5 °C

Procedure

Tryptophan methyl ester hydrochloride (382 mg, 1.5 mmole) was dissolved in dry chloroform (15 ml) and combined with triethylamine (633 μl, 4.5 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 18 h stirring at RT, the reaction mixture was clear. (4-Aminomethyl-1-phenyl-cyclohexyl)-dimethylamine (348.55 mg, 1.5 mmole), dissolved in chloroform (10 ml), was added at RT. After a reaction time of 48 h, the batch was washed 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 (100 g); eluent: MeOH/EE 1:4 (1500 ml) and MeOH/EE 1:1 (500 ml)]. The more nonpolar diastereoisomer of 2-[3-(4-dimethylamino-4-phenylcyclohexylmethyl)thioureido]-3-(1H-indol-3-yl)propionic acid methyl ester (193 mg, m.p. 178-183° C., 26%) and also the more polar diastereoisomer of 2-[3-(4-dimethylamino-4-phenylcyclohexyl-methyl)thioureido]-3-(1H-indol-3-yl)propionic acid methyl ester (157 mg, m.p. 228-234° C., 21%) were light yellow solids.

Workup

  1. additionwas then added dropwise
  2. customresulting in the formation of a precipitate
  3. additionwas added at RT
  4. washAfter a reaction time of 48 h, the batch was washed 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 (100 g); eluent: MeOH/EE 1:4 (1500 ml) and MeOH/EE 1:1 (500 ml)]

Sources & evidence

ORD record
ord-b541f9f0a101438ab0277c77bce4c624
Source dataset
uspto-grants-2008_03
Patent number
US07348354B2

Reaction notes

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