Dimethylformamide → Racemic 4'-fluoro-2'-(2-fluoro-2-methylpropoxy)-7'-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 455648Notes

Reaction equation

HRID 455648 reaction equation
[NH2:1][C:2]1[CH2:29][O:28][CH2:27][C:4]2([C:17]3[CH:16]=[C:15]([OH:18])[CH:14]=[C:13]([F:19])[C:12]=3[O:11][C:10]3[C:5]2=[CH:6][C:7]([C:20]2[C:21]([F:26])=[N:22][CH:23]=[CH:24][CH:25]=2)=[CH:8][CH:9]=3)[N:3]=1.CN(C=O)C.FC(F)(F)S(O[CH2:41][C:42]([F:45])([CH3:44])[CH3:43])(=O)=O>O>[F:19][C:13]1[C:12]2[O:11][C:10]3[C:5](=[CH:6][C:7]([C:20]4[C:21]([F:26])=[N:22][CH:23]=[CH:24][CH:25]=4)=[CH:8][CH:9]=3)[C:4]3([N:3]=[C:2]([NH2:1])[CH2:29][O:28][CH2:27]3)[C:17]=2[CH:16]=[C:15]([O:18][CH2:41][C:42]([F:45])([CH3:44])[CH3:43])[CH:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 121655342-Fluoro-2-methylpropyl trifluoromethanesulfonateHCID 674401225-Amino-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-2'-ol

Product 1

HCID 53390312Racemic 4'-fluoro-2'-(2-fluoro-2-methylpropoxy)-7'-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amineYield 73.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 5-amino-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-2′-ol (200 mg, 0.506 mmol) in DMF (2529 μL) cesium carbonate (330 mg, 1.012 mmol), KI (25.2 mg, 0.152 mmol) and 2-fluoro-2-methylpropyl trifluoromethanesulfonate (125 mg, 0.556 mmol) were added sequentially and the resulting mixture was stirred overnight at RT. The mixture was diluted with 5 ml of water and stirred for 5 minutes. The solvents were decanted from a precipitated gummy solid. 10 ml of water was added and the mixture was stirred for 1 hr at RT at which point a fine precipitate formed. The solids were filtered, washed with water and dried on air for 3 hr, then overnight in vacuo to afford racemic 4′-fluoro-2′-(2-fluoro-2-methylpropoxy)-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (175 mg, 73% yield).

Workup

  1. stirringstirred for 5 minutes
  2. customThe solvents were decanted from a precipitated gummy solid
  3. addition10 ml of water was added
  4. stirringthe mixture was stirred for 1 hr at RT at which point a fine precipitate
  5. customformed
  6. filtrationThe solids were filtered
  7. washwashed with water
  8. customdried on air for 3 hr

Sources & evidence

ORD record
ord-1c91ded30c6a481bb8dac71e82e02b13
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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