1,1'-Carbonyldiimidazole → HCID 53476589, compound

HRID 1505218Notes

Reaction equation

HRID 1505218 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[N:5][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:8]=1.C1N=CN([C:18]([N:20]2C=N[CH:22]=[CH:21]2)=[O:19])C=1.NC1C2[O:32][CH2:33][C:34](=[O:36])[NH:35][C:30]=2[CH:29]=[CH:28][CH:27]=1>C1COCC1.CN(C=O)C>[O:36]=[C:34]1[NH:35][C:30]2[CH:29]=[CH:28][CH:27]=[C:21]([NH:20][C:18]([NH:1][CH2:2][C:3]3[CH:4]=[N:5][C:6]([C:9]([F:12])([F:10])[F:11])=[CH:7][CH:8]=3)=[O:19])[C:22]=2[O:32][CH2:33]1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27377185-(Aminomethyl)-2-(trifluoromethyl)pyridineHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 53476589HCID 53476589, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-aminomethyl-6-trifluoromethylpyridine (1 g, 4.7 mmol) in THF (30 mL) was added CDI (2.1 mol eq) and the mixture was heated at 70° C. overnight. The reaction mixture was evaporated, water was added and the aqueous phase was extracted with EtOAc (3×20 mL). The recombined organic phases were anhydrified over Na2SO4 and evaporated at reduced pressure. The oil obtained (0.8 g, 2.96 mmol) was dissolved in DMF (20 mL) and the bicyclic amine 1f was added (0.8 mol eq, 0.47 g), then the mixture obtained was heated at 100° C. overnight. The solvent was removed at reduced pressure and the residue was purified by chromatography (100% EtOAc) to obtain the product as a pale yellow solid (0.37 g, 42% Yield). 1HNMR (DMSO, 200 MHz) δ 4.39 (d, 2H, J=6), 4.61 (s, 2H), 6.46 (dd, 1H, J=2), 6.81 (t, 1H, J=8), 7.43 (t, 1H), 7.68 (dd, 1H, J=2), 7.90 (m, 2H), 8.18 (s, 1H), 8.69 (s, 1H), 10.66 (s, 1H). [M+1] 355.88 (C15H13F3N3O3 requires 355.27).

Workup

  1. customThe reaction mixture was evaporated
  2. additionwater was added
  3. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
  4. customevaporated at reduced pressure
  5. customThe oil obtained (0.8 g, 2.96 mmol)
  6. custom0.47 g), then the mixture obtained
  7. temperaturewas heated at 100° C. overnight
  8. customThe solvent was removed at reduced pressure
  9. customthe residue was purified by chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-2dc5fe89b7f0480fb049b28a9719f727
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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