(+/-)-N-{2-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-pteridin-2-yl)-2-methyl-propylamino]-1,1-dimethyl-ethyl}-3-fluoro-4-methyl-benzamide → (+/-)-3-benzyl-7-chloro-2-{1-[2-(3-fluoro-4-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-pteridin-4-one

HRID 2055647Notes

Reaction equation

HRID 2055647 reaction equation
[CH2:1]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[N:12][C:13]([Cl:19])=[CH:14][N:15]=2)[N:10]=[C:9]1[CH:20]([NH:24][CH2:25][C:26]([NH:29][C:30](=O)[C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([F:38])[CH:32]=1)([CH3:28])[CH3:27])[CH:21]([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>P(Cl)(Cl)(Cl)=O>[CH2:1]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[N:12][C:13]([Cl:19])=[CH:14][N:15]=2)[N:10]=[C:9]1[CH:20]([N:24]1[CH2:25][C:26]([CH3:27])([CH3:28])[N:29]=[C:30]1[C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([F:38])[CH:32]=1)[CH:21]([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 22172604(+/-)-N-{2-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-pteridin-2-yl)-2-methyl-propylamino]-1,1-dimethyl-ethyl}-3-fluoro-4-methyl-benzamide

Product 1

HCID 22172637(+/-)-3-benzyl-7-chloro-2-{1-[2-(3-fluoro-4-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-pteridin-4-one

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

Formula I where R2 is H; R3 is Cl; R5 is Benzyl; R6 is Isopropyl; R6′ is H; R7 taken together with R8 is 2-(3-Fluoro-4-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl-; W and Z are —N═; X and Y are —C═: A solution of (±)-N-{2-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-pteridin-2-yl)-2-methyl-propylamino]-1,1-dimethyl-ethyl}-3-fluoro-4-methyl-benzamide (121 mg, 0.219 mmol) in phosphorus oxychloride (2 mL) is heated at reflux. After 8 hours, the reaction mixture is allowed to cool to ambient temperature and concentrated under reduced pressure. The residue is dissolved in dichloromethane (10 mL) and washed with two 10 mL portions of saturated aqueous sodium bicarbonate. The combined aqueous layers are extracted with dichloromethane and the extracts are dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is purified by silica gel chromatography (3% methanol/dichloromethane) to give the title compound, (±)-3-benzyl-7-chloro-2-{1-[2-(3-fluoro-4-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-pteridin-4-one.

Workup

  1. temperatureat reflux
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue is dissolved in dichloromethane (10 mL)
  4. washwashed with two 10 mL portions of saturated aqueous sodium bicarbonate
  5. extractionThe combined aqueous layers are extracted with dichloromethane
  6. dry with materialthe extracts are dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified by silica gel chromatography (3% methanol/dichloromethane)

Sources & evidence

ORD record
ord-5b1570a6282c466ebababc982221cee4
Source dataset
uspto-grants-2008_02
Patent number
US07332498B2

Reaction notes

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