1,1'-Carbonyldiimidazole → HCID 53476704, compound

HRID 1505230Notes

Reaction equation

HRID 1505230 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([N:13]([CH3:15])[CH3:14])=[N:5][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:8]=1.C1N=CN([C:21](N2C=NC=C2)=[O:22])C=1.[NH2:28][C:29]1[C:34]2[O:35][CH2:36][C:37](=[O:39])[NH:38][C:33]=2[CH:32]=[CH:31][CH:30]=1>C1COCC1.CN(C=O)C>[CH3:14][N:13]([CH3:15])[C:4]1[C:3]([CH2:2][NH:1][C:21]([NH:28][C:29]2[C:34]3[O:35][CH2:36][C:37](=[O:39])[NH:38][C:33]=3[CH:32]=[CH:31][CH:30]=2)=[O:22])=[CH:8][CH:7]=[C:6]([C:9]([F:10])([F:11])[F:12])[N:5]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-oneHCID 58873632HCID 58873632, compound

Product 1

HCID 53476704HCID 53476704, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 29d (0.78 g, 3.5 mmol) in THF (35 mL) was added CDI (2.1 mol eq, 1.21 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 (3×25 mL). The recombined organic phases were anhydrified over Na2SO4 and evaporated at reduced pressure (pale orange oil, quantitative yield). The oil obtained (0.46 g) was dissolved in DMF (25 mL) and the bicyclic amine 1f was added (0.8 mol eq, 0.2 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 (7:3 EtOAc:petroleum ether) to obtain the product as a pale yellow solid (0.12 g, 21% Yield). 1HNMR (DMSO, 400 MHz) δ 2.84 (s, 6H), 4.36 (d, 2H, J=6), 4.62 (s, 2H), 6.49 (dd, 1H), 6.80 (t, 1H), 7.36 (m, 2H), 7.73 (m, 2H), 8.20 (s, 1H), 10.66 (bs, 1H). [M+1] 410.02 (C18H18F3N5O3 requires 409.36).

Workup

  1. customThe reaction mixture was evaporated
  2. additionwater was added
  3. extractionthe aqueous phase was extracted with EtOAc (3×25 mL)
  4. customevaporated at reduced pressure (pale orange oil, quantitative yield)
  5. customThe oil obtained (0.46 g)
  6. custom0.2 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 (7:3 EtOAc:petroleum ether)

Sources & evidence

ORD record
ord-202e6b23a8f648b087d0c20677b7983b
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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