Methanol → HCID 53475695, compound

HRID 1505160Notes

Reaction equation

HRID 1505160 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[C:5]([N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[CH:4]=1.ClC(Cl)(O[C:22](=[O:28])OC(Cl)(Cl)Cl)Cl.[N-:30]=[C:31]=O.CO.[CH3:35][N:36]([CH:38]=[O:39])C>CCOC(C)=O>[F:17][C:2]([F:16])([F:1])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:38]([NH:36][C:35]2[C:31]3[NH:30][C:22](=[O:28])[NH:10][C:9]=3[CH:6]=[CH:5][CH:4]=2)=[O:39])=[C:5]([N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[CH:4]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 94429TriphosgeneHCID 105034IsocyanateHCID 67424628HCID 67424628, compound

Product 1

HCID 53475695HCID 53475695, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

Amine 2e (600 mg, 2.48 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (755 mg, 1 equiv.) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 10 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1a (450 mg, 3 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 9.5/MeOH 0.5). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 110 mg of an orange solid. Yield=10% 1HNMR (DMSO, 200 MHz) δ 4.30 (2H, d, J=6 Hz), 6.64 (1H, dd, J=7.4 Hz, J′=1.2 Hz), 6.79 (2H, m), 6.91 (1H, dd), 7.83 (1H, d), 7.92 (2H, d), 8.33 (1H, bs), 8.42 (1H, bs), 9.07 (1H, bs), 9.94 (1H, bs), 10.59 (1H, bs); [M+1] 418.2 (C18H14F3N7O2 requires 417.34).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutionthe residue was dissolved in 10 ml of DMF
  4. temperaturethe mixture was warmed at 80° C. for 8 hours
  5. customThe solvent was evaporated
  6. dissolutionthe crude was dissolved in AcOEt (30 ml)
  7. washwashed with water (1×20 ml) and brine
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe purification of the crude residue by chromatographic column

Sources & evidence

ORD record
ord-48d758b3c3fa46e1bd66cf4f3f306305
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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