Ammonia → HCID 68649417, compound

HRID 229371Notes

Reaction equation

HRID 229371 reaction equation
Cl.O[CH:3]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([CH3:17])[CH:10]=1)[C:4](=[NH:8])OCC.[CH2:18]([O:21][C:22]1[CH:23]=[C:24]([Mg]Br)[CH:25]=[CH:26][CH:27]=1)[CH2:19][CH3:20].[CH:30]([N:33](C(C)C)CC)(C)[CH3:31].S(Cl)(Cl)=O.[NH3:43]>C(Cl)(Cl)Cl.C(#N)C>[NH:33]1[CH2:30][CH2:31][N:8]=[C:4]1[C:3]([NH2:43])([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([CH3:17])[CH:10]=1)[C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([O:21][CH2:18][CH2:19][CH3:20])[CH:27]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 68649421HCID 68649421, compoundHCID 178458400HCID 178458400, compound

Product 1

HCID 68649417HCID 68649417, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
-78 °C

Procedure

Using a procedure analogous to the one disclosed in U.S. Pat. No. 3,926,994 and employing ethyl 2-hydroxy-2-(4-methoxy-3-methylphenyl)ethanimidoate hydrochloride salt with 1,2-ethyldiamine, and subsequent reaction with 3-propyloxy phenylmagnesium bromide was dissolved in chloroform (20 mL) gave a reaction mixture. Diisopropylethylamine (2 mL) was added to the reaction mixture, followed by thionyl chloride (1 mL). After 1 hour the reaction mixture was diluted with acetonitrile and cooled to −78° C. The reaction solution was saturated with gaseous ammonia (20 g). The flask was sealed and warmed up to room temperature. After 1 hour the solution was again cooled down to −78° C. and the ammonia was slowly evaporated. Following the removal of ammonia, the remaining solvents were evaporated and the residue was taken up in ethyl acetate, filtered through a pad of silica. The silica pad was eluted with ethyl acetate, then with (40/5/5) ethyl acetate/methanol/ammonium hydroxide. The eluents were combined and concentrated in vacuo to afford [4,5-Dihydro-1H-imidazol-2-yl(4-methoxy-3-methylphenyl)(3-propoxyphenyl)methyl]amine as a yellow amorphous solid (0.6 g), characterized by LCMS analysis. LCMS Conditions: HP 1100 HPLC system; Waters Xterra MS C18, 2 mm (i.d.)×50 mm (length), 3.5 um column, set at 50° C.; Flow rate 1.0 mL/min; Solvent A: 0.02% NH4OH in water; Solvent B 0.02% NH4OH in ACN; Gradient: Time O: 10% B; 2.5 min 90% B; 3 min 90% B; Sample concentration: ˜2.0 mM; Injection volume: 5 uL; Detection: 220 nm, 254 nm DAD.

Workup

  1. customgave a reaction mixture
  2. customThe flask was sealed
  3. temperaturewarmed up to room temperature
  4. temperatureAfter 1 hour the solution was again cooled down to −78° C.
  5. customthe ammonia was slowly evaporated
  6. customthe removal of ammonia
  7. customthe remaining solvents were evaporated
  8. filtrationfiltered through a pad of silica
  9. washThe silica pad was eluted with ethyl acetate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-170fdec245f44cca8c4c7ac9c08cd2f8
Source dataset
uspto-grants-2009_07
Patent number
US07563796B2

Reaction notes

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