Sodium Formate → HCID 78320808, compound

HRID 930282Notes

Reaction equation

HRID 930282 reaction equation
[NH2:1][C:2]1[O:3][C@H:4]([C:31]([F:34])([F:33])[F:32])[CH2:5][C@:6]([C:10]2[CH:11]=[C:12]([NH:17][C:18]([C:20]3[N:21]=[C:22]4[CH:27]=[CH:26][C:25](Cl)=[CH:24][N:23]4[C:29]=3[CH3:30])=[O:19])[CH:13]=[CH:14][C:15]=2[F:16])([CH2:8][F:9])[N:7]=1.C([O-])=O.[Na+]>>[NH2:1][C:2]1[O:3][C@H:4]([C:31]([F:34])([F:33])[F:32])[CH2:5][C@:6]([C:10]2[CH:11]=[C:12]([NH:17][C:18]([C:20]3[N:21]=[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]4[C:29]=3[CH3:30])=[O:19])[CH:13]=[CH:14][C:15]=2[F:16])([CH2:8][F:9])[N:7]=1

Participants

3

Reactant 2

HCID 2723810Sodium FormateHCID 86732111HCID 86732111, compound

Product 1

HCID 78320808HCID 78320808, compoundYield 81%

Conditions

Temperature
110 °C

Procedure

A sealable vial was charged with N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-6-chloro-3-methylimidazo[1,2-a]pyridine-2-carboxamide (0.0513 g, 0.102 mmol, Example 6), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (7.24 mg, 10.22 μmol) and sodium formate (21 mg, 0.307 mmol, Alfa Aesar). The sealed vial was evacuated and backfilled with nitrogen. DMF (1.3 ml) was added and the reaction was stirred in a preheated 110° C. oil bath for 1 hour. The reaction was cooled to RT and partitioned between water and EtOAc. The organic layer was separated, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude residue was purified by silica gel flash chromatography using a gradient of 10-100% EtOAc in hexanes to afford the title compound as a white solid. (0.0385 g, 0.082 mmol, 81% yield). MS m/z=467.9 [M+H]+. Calculated for C21H18F5N5O2: 467.39

Workup

  1. customThe sealed vial was evacuated
  2. additionDMF (1.3 ml) was added
  3. temperatureThe reaction was cooled to RT
  4. custompartitioned between water and EtOAc
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-371a13bdced744d0964d5efd1645084f
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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