Dicyclohexylcarbodiimide → 7-Bromo-3-chloro-1-methoxy-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazin]-2'-amine

HRID 931575Notes

Reaction equation

HRID 931575 reaction equation
[NH2:1][C:2]1([CH2:19][CH2:20][OH:21])[C:15]2[CH:14]=[C:13]([Cl:16])[N:12]=[C:11](F)[C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:18])=[CH:6][CH:7]=2.[N+:22]([C:25]1C=CC(C(N=C=S)=O)=CC=1)([O-])=O.C1(N=C=NC2CCCCC2)CCCCC1.[C:51](=O)([O-])[O-:52].[K+].[K+]>C1COCC1>[Br:18][C:5]1[CH:4]=[C:3]2[C:2]3([CH2:19][CH2:20][O:21][C:25]([NH2:22])=[N:1]3)[C:15]3[CH:14]=[C:13]([Cl:16])[N:12]=[C:11]([O:52][CH3:51])[C:10]=3[O:9][C:8]2=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 11430Potassium CarbonateHCID 1413984-Nitrobenzoyl isothiocyanateHCID 866583632-(5-amino-7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-yl)ethanol

Product 1

HCID 584658837-Bromo-3-chloro-1-methoxy-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazin]-2'-amineYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(5-amino-7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-yl)ethanol (0.50 g, 1.338 mmol) in THF (10 mL) was added 4-nitrobenzoyl isothiocyanate (0.306 g, 1.472 mmol) and the reaction mixture was stirred at RT for 25 min. TEA (0.019 mL, 0.134 mmol) and 1,3-dicyclohexylcarbodiimide (0.304 g, 1.472 mmol) were added and the reaction mixture was heated at 70° C. for 1.5 h. The reaction mixture was allowed to warm to RT and concentrated under reduced pressure. The residue was dissolved in MeOH (15 mL) and potassium carbonate (0.555 g, 4.01 mmol) was added. The resulting mixture was stirred at rt overnight. The reaction mixture was concentrated under reduced pressure, washed with water and extracted with DCM. The combined organic layers were dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by chromatography (0-40% EtOAc/hexanes) to afford 7-bromo-3-chloro-1-methoxy-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-2′-amine (0.45 g, 1.096 mmol, 82% yield) as a yellow solid.

Workup

  1. temperaturethe reaction mixture was heated at 70° C. for 1.5 h
  2. temperatureto warm to RT
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in MeOH (15 mL)
  5. stirringThe resulting mixture was stirred at rt overnight
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. washwashed with water
  8. extractionextracted with DCM
  9. dry with materialThe combined organic layers were dried over Na2SO4
  10. customthe solvent was removed under reduced pressure
  11. customThe residue was purified by chromatography (0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8ed4c9f5dea24868b9b8c573833da33d
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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