Phosgene → HCID 10409330, compound

HRID 2216961Notes

Reaction equation

HRID 2216961 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[C:5]([CH:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[CH3:18])=[CH:4][N:3]=1.C(N(CC)CC)C.[C:35](Cl)(Cl)=[O:36]>ClCCl>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)[C:35](=[O:36])[N:19]([C:20]3[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=3)[CH:17]([CH3:18])[C:5]2=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 8471TriethylamineHCID 10475144HCID 10475144, compound

Product 1

HCID 10409330HCID 10409330, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (±)-{2-chloro-5-[1-(4-methoxy-phenylamino)-ethyl]-pyrimidin-4-yl}-(4-methoxy-phenyl)-amine (49.4 mg; 0.13 mmol) (from Example 1f supra) in dichloromethane (1.5 mL) was cooled in an ice-water bath. To this solution was added triethylamine (0.18 mL; 1.29 mmol) (Aldrich), followed by phosgene solution (1.89 M, 0.34 mL; 0.64 mmol) (Fluka). After two hours in the cold, the reaction was diluted with additional dichloromethane and washed sequentially with water, dilute aqueous hydrochloric acid, dilute aqueous sodium bicarbonate, and brine. The organic layer was then dried over anhydrous sodium sulfate and concentrated. Residue was purified by flash chromatography (Biotage, 12M, 40:60 ethyl acetate-hexanes as solvent) to give (±)-7-chloro-1,3-bis-(4-methoxy-phenyl)-4-methyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a white solid. (Yield 42.6 mg; 79.2%).

Workup

  1. washwashed sequentially with water, dilute aqueous hydrochloric acid, dilute aqueous sodium bicarbonate, and brine
  2. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customResidue was purified by flash chromatography (Biotage, 12M, 40:60 ethyl acetate-hexanes as solvent)

Sources & evidence

ORD record
ord-0eccc8d8a5b043f1acfc78e85a173bb1
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

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