Benzyl isocyanate → HCID 178484258, compound

HRID 1465902Notes

Reaction equation

HRID 1465902 reaction equation
[F:1][C:2]1[C:3]([N:9]=[CH:10][N:11]([CH3:13])[CH3:12])=[N:4][C:5]([OH:8])=[N:6][CH:7]=1.[CH2:14]([N:21]=[C:22]=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(Cl)Cl>[CH2:14]([NH:21][C:22]([N:6]1[CH:7]=[C:2]([F:1])[C:3](/[N:9]=[CH:10]/[N:11]([CH3:13])[CH3:12])=[N:4][C:5]1=[O:8])=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 76639Benzyl isocyanateHCID 178484257HCID 178484257, compound

Product 1

HCID 178484258HCID 178484258, compoundYield 62.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of N′-(5-fluoro-2-hydroxy-pyrimidin-4-yl)-N,N-dimethylformamidine (0.25 g, 1.35 mmol) in CH2Cl2 (5 mL) was added benzyl isocyanate (0.187 mL, 1.49 mmol) forming a solution that was stirred at room temperature overnight. The mixture was diluted with CH2Cl2 (100 mL) and was washed with brine (2×50 mL). The combined aqueous layers were extracted with CH2Cl2 (2×25 mL). The organic extracts were dried over sodium sulfate (Na2SO4), filtered and concentrated. The residue was purified by normal phase chromatography (gradient, methanol/CH2Cl2) and then by reverse phase chromatography (gradient, acetonitrile (CH3CN) in water (H2O)). The resulting solution was concentrated under reduced pressure forming a precipitate. The mixture was extracted with CH2Cl2 (4×100 mL), dried (Na2SO4), filtered and concentrated to yield (E)-N-benzyl-4-((dimethylamino)methyleneamino)-5-fluoro-2-oxopyrimidine-1(2H)-carboxamide (0.268 g, 62%) as a white solid: mp 147-150° C.; 1H NMR (300 MHz, CDCl3) δ 10.83 (t, J=4.94 Hz, 1H), 8.81 (s, 1H), 8.44 (d, J=6.59 Hz, 1H), 7.32-7.22 (m, 5H), 4.56 (d, J=5.93 Hz, 2H), 3.21 (s, 3H), 3.20 (s, 3H); ESIMS m/z 318.2 ([M+H]+).

Workup

  1. customforming a solution that
  2. washwas washed with brine (2×50 mL)
  3. extractionThe combined aqueous layers were extracted with CH2Cl2 (2×25 mL)
  4. dry with materialThe organic extracts were dried over sodium sulfate (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by normal phase chromatography (gradient, methanol/CH2Cl2)
  8. concentrationThe resulting solution was concentrated under reduced pressure
  9. customforming a precipitate
  10. extractionThe mixture was extracted with CH2Cl2 (4×100 mL)
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-b3dee78beefc45eeb9fb53751aa5b2dc
Source dataset
uspto-grants-2015_04
Patent number
US09000002B2

Reaction notes

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