1,1'-Carbonyldiimidazole → HCID 53476819, compound

HRID 1505234Notes

Reaction equation

HRID 1505234 reaction equation
[NH2:1][CH2:2][C:3]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:4]=1[O:5][CH2:6][CH2:7][N:8]([CH3:10])[CH3:9].C1N=CN([C:24](N2C=NC=C2)=[O:25])C=1.[NH2:31][C:32]1[C:37]2[O:38][CH2:39][C:40](=[O:42])[NH:41][C:36]=2[CH:35]=[CH:34][CH:33]=1>C1COCC1.CN(C=O)C>[CH3:9][N:8]([CH3:10])[CH2:7][CH2:6][O:5][C:4]1[CH:11]=[C:12]([C:15]([F:16])([F:17])[F:18])[CH:13]=[CH:14][C:3]=1[CH2:2][NH:1][C:24]([NH:31][C:32]1[C:37]2[O:38][CH2:39][C:40](=[O:42])[NH:41][C:36]=2[CH:35]=[CH:34][CH:33]=1)=[O:25]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-oneHCID 67449947HCID 67449947, compound

Product 1

HCID 53476819HCID 53476819, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 27b (1.48 g, 5.64 mmol) in THF (25 mL) was added CDI (2.1 mol eq, 1.92 g) 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 (3×30 mL). The recombined organic phases were anhydrified over Na2SO4 and evaporated at reduced pressure (pale yellow oil, 1.91 g, 95% yield). The oil obtained (0.95 g, 2.68 mmol) was dissolved in DMF (20 mL) and the bicyclic amine 1f was added (0.8 mol eq, 0.35 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 (8:2 EtOAc:MeOH) to obtain the product as a white solid (0.33 g, 35% Yield). 1HNMR (DMSO, 400 MHz) δ 2.27 (s, 6H), 2.71 (t, 2H), 4.20 (t, 2H), 4.32 (d, 2H, J=6), 4.62 (s, 2H), 6.50 (dd, 1H), 6.80 (t, 1H), 7.29 (m, 3H), 7.40 (d, 1H), 7.70 (dd, 1H), 8.18 (s, 1H), 10.65 (bs, 1H). [M+1] 452.91 (C21H23F3N4O4 requires 452.43).

Workup

  1. customThe reaction mixture was evaporated
  2. additionwater was added
  3. extractionthe aqueous phase was extracted with EtOAc (3×30 mL)
  4. customevaporated at reduced pressure (pale yellow oil, 1.91 g, 95% yield)
  5. customThe oil obtained (0.95 g, 2.68 mmol)
  6. custom0.35 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 (8:2 EtOAc:MeOH)

Sources & evidence

ORD record
ord-440de13908354cf9b8de08bbdaa5b242
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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