Benzyl chloroformate → HCID 58365044, compound

HRID 60335Notes

Reaction equation

HRID 60335 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:17]=[N:16][C:7]2[NH:8][C:9]3[CH:14]=[N:13][CH:12]=[C:11]([OH:15])[C:10]=3[C:6]=2[CH:5]=1.Cl[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>CN(C=O)C>[CH2:22]([O:21][C:19]([N:8]1[C:9]2[CH:14]=[N:13][CH:12]=[C:11]([OH:15])[C:10]=2[C:6]2[CH:5]=[C:4]([Br:3])[CH:17]=[N:16][C:7]1=2)=[O:20])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 24758Sodium hydrideHCID 58364979HCID 58364979, compound

Product 1

HCID 58365044HCID 58365044, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (167 mg, 4.17 mmol) was added to a cooled (0° C.) mixture of 3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-5-ol (1.0 g, 3.79 mmol) in DMF (15 mL). On complete addition the mixture was stirred for 15 minutes then allowed to warm to ambient temperature and stirred for 15 minutes. A solution of benzyl chloroformate (610 mg, 3.6 mmol) in DMF (1 mL) was added and stirring continued for 18 hours. The solvent was evaporated and the resultant residue diluted with water and extracted with dichloromethane (5×50 mL) and ethyl acetate (3×30 mL). The combined organic layer was dried over (Na2SO4), filtered and evaporated to afford a residue. The resultant residue was purified by flash chromatography (silica, 12 g cartridge, ISCO, 0-7% methanol in dichloromethane). The appropriate fractions were collected and evaporated to afford the title compound as a light yellow solid (240 mg, 17%). LCMS (Method B): RT=4.54 min, M+H+=398/400. 1H NMR (400 MHz, DMSO-d6): 8.99 (s, 1H), 8.79 (d, J=2.4 Hz, 1H), 8.63 (d, J=2.4 Hz, 1H), 8.23 (s, 1H), 7.63 (d, J=7.5 Hz, 2H), 7.48-7.36 (m, 3H), 5.61 (s, 2H).

Workup

  1. temperaturea cooled
  2. additionOn complete addition the mixture
  3. stirringstirred for 15 minutes
  4. stirringstirring
  5. waitcontinued for 18 hours
  6. customThe solvent was evaporated
  7. additionthe resultant residue diluted with water
  8. extractionextracted with dichloromethane (5×50 mL) and ethyl acetate (3×30 mL)
  9. dry with materialThe combined organic layer was dried over (Na2SO4)
  10. filtrationfiltered
  11. customevaporated
  12. customto afford a residue
  13. customThe resultant residue was purified by flash chromatography (silica, 12 g cartridge, ISCO, 0-7% methanol in dichloromethane)
  14. customThe appropriate fractions were collected
  15. customevaporated

Sources & evidence

ORD record
ord-0573ccd3018a41fd85a82505220a26dc
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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