Potassium Acetate → 2,8-di(pyridin-3-yl)-5'H-spiro[chromeno[3,2-b]pyridine-10,4'-oxazol]-2'-amine

HRID 1970294Notes

Reaction equation

HRID 1970294 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]2[O:8][C:9]3[C:10]([C:16]4([CH2:20][O:19][C:18]([NH2:21])=[N:17]4)[C:4]=2[CH:3]=1)=[N:11][C:12](Cl)=[CH:13][CH:14]=3.[C:22]([O-])(=O)[CH3:23].[K+].[N:27]1[CH:32]=[CH:31][CH:30]=[C:29](B(O)O)[CH:28]=1>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:12]2[N:11]=[C:10]3[C:16]4([C:4]5[CH:3]=[C:2]([C:9]6[CH:10]=[N:11][CH:12]=[CH:22][CH:23]=6)[CH:7]=[CH:6][C:5]=5[O:8][C:9]3=[CH:14][CH:13]=2)[CH2:20][O:19][C:18]([NH2:21])=[N:17]4)[CH:28]=1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 27343783-Pyridinylboronic acidHCID 584661508-bromo-2-chloro-5'H-spiro[chromeno[3,2-b]pyridine-10,4'-oxazol]-2'-amine

Product 1

HCID 584662342,8-di(pyridin-3-yl)-5'H-spiro[chromeno[3,2-b]pyridine-10,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

A mixture of the 8-bromo-2-chloro-5′H-spiro[chromeno[3,2-b]pyridine-10,4′-oxazol]-2′-amine (from step 6, 40.0 mg, 0.109 mmol), potassium acetate (27.3 μL, 0.436 mmol), dichlorobis(triphenyl-phosphine)palladium (ii) (3.83 mg, 5.46 μmol) and 3-pyridylboronic acid (40.2 mg, 0.327 mmol) in 1.5 ml of dioxane/water=2:1 was heated at 110° C. under microwave irradiation for 15 min. LCMS and TLC showed incomplete conversion after 15 min. The reaction was re-heated in the microwave at 130° C. for 20 additional min. After cooling, the reaction mixture was purified by column chromatography (SiO2, DCM to DCM/MeOH=100:1 to 100:5 to 100:10 to 100:20) to afford 2,8-di(pyridin-3-yl)-5′H-spiro[chromeno[3,2-b]pyridine-10,4′-oxazol]-2′-amine as a gum. MS (M+1): 408.0; and 2-chloro-8-(pyridin-3-yl)-5′H-spiro[chromeno[3,2-b]pyridine-10,4′-oxazol]-2′-amine also as a gum. MS (M+1): 365.0.

Workup

  1. customafter 15 min
  2. temperatureThe reaction was re-heated in the microwave at 130° C. for 20 additional min
  3. temperatureAfter cooling
  4. customthe reaction mixture was purified by column chromatography (SiO2, DCM to DCM/MeOH=100:1 to 100:5 to 100:10 to 100:20)

Sources & evidence

ORD record
ord-6488120e596043398af9c644bea15ed2
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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