Triethylamine → (R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-urea

HRID 1243223Notes

Reaction equation

HRID 1243223 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH2:9][NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH3:18])=[CH:13][CH:12]=2)=[CH:4][N:3]=1.[N+](C1C=CC([O:28][C:29](=O)[NH:30][C@H:31]([CH3:41])[CH2:32][O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])=CC=1)([O-])=O.C(N(CC)CC)C>C1(C)C=CC=CC=1>[C:37]([Si:34]([CH3:36])([CH3:35])[O:33][CH2:32][C@H:31]([NH:30][C:29](=[O:28])[N:10]([CH2:9][C:5]1[C:6]([Cl:8])=[N:7][C:2]([Cl:1])=[N:3][CH:4]=1)[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH3:18])=[CH:13][CH:12]=1)[CH3:41])([CH3:40])([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11426039(2,4-Dichloro-pyrimidin-5-yl-methyl)-(4-ethyl-phenyl)-amineHCID 58715060(R)-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-carbamic acid 4-nitro-phenyl ester

Product 1

HCID 11488861(R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of (2,4-dichloro-pyrimidin-5-yl-methyl)-(4-ethyl-phenyl)amine (620 mg, 2.19 mmol) (from Example 38c supra), (R)-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-carbamic acid 4-nitro-phenyl ester (778 mg, 2.19 mmol) (from Example 38b supra) and triethylamine (0.93 mL, 6.6 mmol) (Allied Signal) in toluene (20 mL) was heated at reflux for 48 hours. The reaction mixture was quenched at room temperature with 1 N aqueous hydrochloric acid then extracted with ethyl acetate. The combined organic layers were successively washed with 1 N aqueous sodium hydroxide solution and brine, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate in hexanes) to give (R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-urea. (Yield 383 mg, 36%).

Workup

  1. temperatureat reflux for 48 hours
  2. customThe reaction mixture was quenched at room temperature with 1 N aqueous hydrochloric acid
  3. extractionthen extracted with ethyl acetate
  4. washThe combined organic layers were successively washed with 1 N aqueous sodium hydroxide solution and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5a39a2a4222c4a658283050c8d385366
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

Loading…