Dimethylformamide → (S)-N-(7-bromo-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazine]-5'-yl)formamide

HRID 455664Notes

Reaction equation

HRID 455664 reaction equation
[CH2:1]([OH:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH3:7][N:8]([CH:10]=[O:11])C.[H-].[Na+].[Br:14][C:15]1[CH:16]=[C:17]2[C@:28]3([N:33]=C(N)[CH2:31][O:30][CH2:29]3)[C:27]3[CH:26]=[C:25](Cl)[N:24]=[CH:23][C:22]=3[O:21][C:18]2=[CH:19][CH:20]=1>C(OCC)(=O)C.O.[Cl-].[Na+].O>[Br:14][C:15]1[CH:16]=[C:17]2[C@:28]3([N:33]=[C:7]([NH:8][CH:10]=[O:11])[CH2:31][O:30][CH2:29]3)[C:27]3[CH:26]=[C:25]([O:6][CH2:1][C:2]([CH3:5])([CH3:4])[CH3:3])[N:24]=[CH:23][C:22]=3[O:21][C:18]2=[CH:19][CH:20]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 6404Neopentyl alcoholHCID 24758Sodium hydrideHCID 58465879(S)-7-bromo-3-chloro-2',6'-dihydrospiro[chromeno [2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

Product 1

HCID 86658384(S)-N-(7-bromo-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazine]-5'-yl)formamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A vial was charged with neopentyl alcohol (0.579 g, 6.57 mmol) and DMF (6.57 mL). Sodium hydride (60% in mineral oil; 0.263 g, 6.57 mmol) was added and the reaction was stirred for 10 minutes at room temperature. The vial was heated to 100° C. for 5 min. The vial was cooled to rt. (S)-7-bromo-3-chloro-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.500 g, 1.314 mmol) was added in one portion. The vial was sealed and heated to 100° C. three hours. The mixture was diluted with ethyl acetate and water. A small amount of brine was added and the layers were separated. The aq. layer was extracted twice with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (0-100% EtOAc/Hexanes) to give 175 mg of (S)—N-(7-bromo-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazine]-5′-yl)formamide as a light yellow solid.

Workup

  1. temperatureThe vial was heated to 100° C. for 5 min
  2. temperatureThe vial was cooled to rt
  3. customThe vial was sealed
  4. temperatureheated to 100° C. three hours
  5. customthe layers were separated
  6. extractionThe aq. layer was extracted twice with ethyl acetate
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography (0-100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-8dcd9304798f489cab057b8651d8bf7c
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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