Sodium Iodide → {4-[1-(4-Chloro-phenyl)-cyclohexyl]-thiazol-2-yl}-[2-(1-methyl-pyrrolidin-2-yl)-ethyl] amine

HRID 7816Notes

Reaction equation

HRID 7816 reaction equation
Cl[CH2:2][C:3]([C:5]1([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=O.[I-].[Na+].[CH3:20][N:21]1[CH2:25][CH2:24][CH2:23][CH:22]1[CH2:26][CH2:27][NH:28][C:29]([NH2:31])=[S:30]>CC(C)=O.C(=O)([O-])O.[Na+].O>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C:5]2([C:3]3[N:31]=[C:29]([NH:28][CH2:27][CH2:26][CH:22]4[CH2:23][CH2:24][CH2:25][N:21]4[CH3:20])[S:30][CH:2]=3)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]2)=[CH:12][CH:13]=1

Participants

7

Reactant 3

HCID 5238Sodium IodideHCID 21992305[2-(1-Methyl-pyrrolidin-yl)ethyl] thioureaHCID 219923432-Chloro-1-[1-(4-chloro-phenyl)-cyclohexyl]-ethanone

Product 1

HCID 21992332{4-[1-(4-Chloro-phenyl)-cyclohexyl]-thiazol-2-yl}-[2-(1-methyl-pyrrolidin-2-yl)-ethyl] amine

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 2-chloro-1-[1-(4-chloro-phenyl)-cyclohexyl]-ethanone (144.8 mg, 0.53 mmol) and sodium iodide (80 mg, 0.53 mmol) in acetone (4 mL) was stirred at room temperature for 10 min. Next, [2-(1-methyl-pyrrolidin-yl)ethyl] thiourea (100 mg, 0.71 mmol) was added. The resulting mixture was heated at 50° C. overnight. After the mixture was allowed to cool to room temperature, it was diluted with 5% sodium hydrogen carbonate in water and then extracted with ethyl acetate (3×20 mL). The extracts were combined, and dried over anhydrous sodium sulfate, filtered and concentrated to give an oil. The crude was purified by column chromatography on silica gel using dichloromethane/2 N ammonia in ethanol (95:5) to give {4-[1-(4-chloro-phenyl)-cyclohexyl]-thiazol-2-yl}-[2-(1-methyl-pyrrolidin-2-yl)-ethyl] amine, 95, as an oil (150 mg, 70%). 1H (CDCl3, 300 MHz) δ 7.30–7.21 (m, 4H), 6.02 (s, 1H), 5.67 (s, 1H), 3.67–1.52 (m, 24H) ppm; 13C(C6D6, 75 MHz) δ 22.9, 23.5, 26.9, 29.4, 30.8, 36.7, 40.8, 43.2, 46.4, 57.4, 64.9, 101.2, 128.7, 129.4, 132.0, 146.8, 160.1, 169.5 ppm.

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give an oil
  7. customThe crude was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-a6a60bac2edd4b239c9aa92fbc731b55
Source dataset
uspto-grants-2006_08
Patent number
US07087623B2

Reaction notes

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