Dimethylformamide → HCID 118036264, compound

HRID 1778074Notes

Reaction equation

HRID 1778074 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:6][CH2:7][CH2:8][N:9]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][N:16]=3)=[O:13])[C:10]=2[N:11]=1.[Li]CCCC.CN([CH:30]=[O:31])C>C1COCC1>[CH:30]([C:2]1[CH:3]=[CH:4][C:5]2[O:6][CH2:7][CH2:8][N:9]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][N:16]=3)=[O:13])[C:10]=2[N:11]=1)=[O:31]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 118036171HCID 118036171, compound2×HCID 178418339Butyllithium

Product 1

HCID 118036264HCID 118036264, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

6-Bromo-N-(5-methylpyridin-2-yl)-2H-pyrido[3,2-b][1,4]oxazine-4(3H)-carboxamide (intermediate 1A, 110 mg, 0.284 mmol) was dissolved in THF (3 ml). The solution was flushed with argon and cooled to −78° C. Subsequently, n-BuLi (1.4 M in hexanes, 0.506 ml, 0.709 mmol) was added drop wise and the mixture was stirred for 1 h at −78° C. before DMF (200 μl, 2.58 mmol) was added. The reaction mixture was stirred for 1 h at −78° C. and then slowly warmed up to room temperature. The reaction mixture was quenched with sat. aq. NH4Cl and diluted with EtOAc. The org. layer was separated, washed with water, dried over Na2SO4, filtered and concentrated. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 80:20 to 0:100) followed by preparative supercritical fluid chromatography (SFC 1, Hilic column) to obtain the title compound as a white solid.

Workup

  1. customThe solution was flushed with argon
  2. additionwas added
  3. temperatureslowly warmed up to room temperature
  4. customThe reaction mixture was quenched with sat. aq. NH4Cl
  5. additiondiluted with EtOAc
  6. customlayer was separated
  7. washwashed with water
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 80:20 to 0:100)

Sources & evidence

ORD record
ord-30b7cbb94ac5472a9c434a54cc75c253
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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