Potassium Carbonate → 4'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 455646Notes

Reaction equation

HRID 455646 reaction equation
Br[C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[C:8]([F:24])=[CH:9][C:10]([O:22][CH3:23])=[CH:11][C:12]=3[C:13]32[N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)=[CH:4][CH:3]=1.[F:25][C:26]1[C:31](B(O)O)=[CH:30][CH:29]=[CH:28][N:27]=1.C(=O)([O-])[O-].[K+].[K+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O1CCOCC1>[F:24][C:8]1[C:7]2[O:6][C:5]3[C:14](=[CH:15][C:2]([C:31]4[C:26]([F:25])=[N:27][CH:28]=[CH:29][CH:30]=4)=[CH:3][CH:4]=3)[C:13]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:12]=2[CH:11]=[C:10]([O:22][CH3:23])[CH:9]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 584659217'-Bromo-4'-fluoro-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

Product 1

HCID 674375114'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amineYield 74.2%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A 250 ml RB flask was charged with 7′-bromo-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (2.73 g, 6.94 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.492 g, 0.694 mmol) and 2-fluoropyridin-3-ylboronic acid (1.467 g, 10.41 mmol). Dioxane (40 mL) and potassium carbonate (1M solution) (20.83 mL, 20.83 mmol) were added and the mixture was flushed with argon and heated at 85° C. for 30 minutes. The mixture was cooled to RT, diluted with EtOAc and the organic layer was separated and concentrated in vacuo to give a yellow semisolid. After trituration with 10 ml of EtOH the solid was filtered, washed with EtOH (2×1 ml) and dried on air overnight to afford 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (2.11 g, 5.15 mmol).

Workup

  1. customthe mixture was flushed with argon
  2. temperatureThe mixture was cooled to RT
  3. additiondiluted with EtOAc
  4. customthe organic layer was separated
  5. concentrationconcentrated in vacuo
  6. customto give a yellow semisolid
  7. filtrationAfter trituration with 10 ml of EtOH the solid was filtered
  8. washwashed with EtOH (2×1 ml)
  9. customdried on air overnight

Sources & evidence

ORD record
ord-b310fed1b87343919060d0b7c51605e7
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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