Phenyl isocyanate → HCID 21946008, compound

HRID 2216969Notes

Reaction equation

HRID 2216969 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH:9]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH2:10][CH3:11])=[CH:4][N:3]=1.[C:21]1([N:27]=[C:28]=[O:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]2[N:27]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:28](=[O:29])[N:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[CH:9]([CH2:10][CH3:11])[C:5]2=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 7672Phenyl isocyanateHCID 21945997HCID 21945997, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 21946008HCID 21946008, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (±)-[1-(2,4-dichloro-pyrimidin-5-yl)-propyl]-(4-methoxy-phenyl)-amine (0.19 g; 0.59 mmol) (from Example 7c supra) in toluene (2 mL) was added phenyl isocyanate (83 μL; 0.76 mmol) (Aldrich). The solution was heated in an oil bath at 110° C. for 1 hour. Upon cooling to room temperature, the reaction was concentrated. The residue was triturated with hexanes and then dried briefly under high vacuum. The solid residue (intermediate urea) was dissolved in freshly distilled tetrahydrofuran (2 mL), cooled to −3° C. and treated with potassium tert-butoxide (1.0 M in tetrahydrofuran; 0.65 mL; 0.65 mmol) (Aldrich). After 15 minutes in the cold, the reaction mixture was filtered through a silica gel pad (1 g) and washed with ethyl acetate. The filtrate was concentrated and purified by flash chromatography (Biotage, 40S, 20:80 to 40:60 ethyl acetate-hexanes gradient) to give (±)-7-chloro-4-ethyl-3-(4-methoxy-phenyl)-1-phenyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a solid. (Yield 0.14 g; 60.2%). The NMR of this material showed only two singlets for the pyrimidine proton indicating a mixture of the desired product and the corresponding 7-bromo compound.

Workup

  1. temperatureUpon cooling to room temperature
  2. concentrationthe reaction was concentrated
  3. customThe residue was triturated with hexanes
  4. customdried briefly under high vacuum
  5. dissolutionThe solid residue (intermediate urea) was dissolved in freshly distilled tetrahydrofuran (2 mL)
  6. temperaturecooled to −3° C.
  7. filtrationAfter 15 minutes in the cold, the reaction mixture was filtered through a silica gel pad (1 g)
  8. washwashed with ethyl acetate
  9. concentrationThe filtrate was concentrated
  10. custompurified by flash chromatography (Biotage, 40S, 20:80 to 40:60 ethyl acetate-hexanes gradient)

Sources & evidence

ORD record
ord-b80889e9b7884d5b962c4b1deac4d40b
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

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