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

HRID 455716Notes

Reaction equation

HRID 455716 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[C:15](B(O)O)=[CH:14][CH:13]=[CH:12][N:11]=1.Br[C:20]1[CH:33]=[CH:32][C:31]2[O:30][C:29]3[C:24](=[CH:25][C:26]([C:34]4[CH:39]=[CH:38][N:37]=[C:36]([F:40])[CH:35]=4)=[CH:27][CH:28]=3)[C@@:23]3([N:45]=[C:44]([NH2:46])[CH2:43][O:42][CH2:41]3)[C:22]=2[CH:21]=1>O1CCOCC1.O.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>[F:9][C:10]1[C:15]([C:20]2[CH:33]=[CH:32][C:31]3[O:30][C:29]4[C:24](=[CH:25][C:26]([C:34]5[CH:39]=[CH:38][N:37]=[C:36]([F:40])[CH:35]=5)=[CH:27][CH:28]=4)[C@@:23]4([N:45]=[C:44]([NH2:46])[CH2:43][O:42][CH2:41]4)[C:22]=3[CH:21]=2)=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 67438537(R)-2'-bromo-7'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

Product 1

HCID 58465971(R)-2'-(2-fluoropyridin-3-yl)-7'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amineYield 68.5%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave vial, the potassium phosphate (0.071 g, 0.334 mmol), PdCl2(AmPhos)2 (7.88 mg, 0.011 mmol), 2-fluoropyridin-3-ylboronic acid (0.020 g, 0.139 mmol), and (R)-2′-bromo-7′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.049 g, 0.111 mmol) were suspended in dioxane (2 mL) and water (0.5 mL). Argon gas was blown through the vessel, which was sealed and heated by microwave at 120° C. for 30 min. The mixture was concentrated, and the residue was diluted with brine (15 mL), and the aqueous phase was extracted with 5% MeOH-dcm (3×25 mL). The organics were combined, dried over sodium sulfate and concentrated. The residue was purified by chromatography (3.5%-4.5% MeOH/DCM) to afford (R)-2′-(2-fluoropyridin-3-yl)-7′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (35 mg, 0.076 mmol). MS (m/z) 457 (M+H)+.

Workup

  1. customwas sealed
  2. concentrationThe mixture was concentrated
  3. additionthe residue was diluted with brine (15 mL)
  4. extractionthe aqueous phase was extracted with 5% MeOH-dcm (3×25 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (3.5%-4.5% MeOH/DCM)

Sources & evidence

ORD record
ord-268b999a275b45ebb52ae6f698650ce3
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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