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

HRID 455645Notes

Reaction equation

HRID 455645 reaction equation
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([C:27]4[C:28]([F:33])=[N:29][CH:30]=[CH:31][CH:32]=4)=[CH:16][C:17]=3[C:18]32[N:25]=[C:24]([NH2:26])[CH2:23][O:22][CH2:21]3)=[C:9]([F:34])[CH:8]=1)(=O)=O.[F:37][C:38]1[CH:43]=[C:42](B(O)O)[CH:41]=[CH:40][N:39]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O1CCOCC1>[F:34][C:9]1[C:10]2[O:11][C:12]3[C:17](=[CH:16][C:15]([C:27]4[C:28]([F:33])=[N:29][CH:30]=[CH:31][CH:32]=4)=[CH:14][CH:13]=3)[C:18]3([N:25]=[C:24]([NH2:26])[CH2:23][O:22][CH2:21]3)[C:19]=2[CH:20]=[C:7]([C:42]2[CH:41]=[CH:40][N:39]=[C:38]([F:37])[CH:43]=2)[CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 867619685-Amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthene]-7'-yl trifluoromethanesulfonate

Product 1

HCID 533903114'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amineYield 85%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A 10 ml resealable tube was charged with 5-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (385 mg, 0.730 mmol), 2-fluoropyridin-4-ylboronic acid (165 mg, 1.168 mmol), PdCl2(dppf)-DCM adduct (59.6 mg, 0.073 mmol), dioxane (3650 pt) and potassium carbonate (1M solution) (2190 μL, 2.190 mmol). The mixture was flushed with argon, sealed and heated at 85° C. for 1 hr. The mixture was diluted with EtOAc, organic layer was filtered through Celite and concentrated. The brown residue was purified by chromatography (10-80% DCM/MeOH/NH4OH in DCM) to afford 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (294 mg, 85% yield) as off-white solid.

Workup

  1. customThe mixture was flushed with argon
  2. customsealed
  3. additionThe mixture was diluted with EtOAc, organic layer
  4. filtrationwas filtered through Celite
  5. concentrationconcentrated
  6. customThe brown residue was purified by chromatography (10-80% DCM/MeOH/NH4OH in DCM)

Sources & evidence

ORD record
ord-471eca44146049348c47147e85ba946b
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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