N,N'-Dimethylethylenediamine → N-((4R)-2-amino-7'-methoxyspiro[1,3-oxazole-4,9'-xanthen]-2'-yl)-5-chloro-2-pyridinecarboxamide

HRID 1970243Notes

Reaction equation

HRID 1970243 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:16][CH3:17])=[CH:9][CH:10]=3)[C:5]3([CH2:21][O:20][C:19]([NH2:22])=[N:18]3)[C:4]=2[CH:3]=1.[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]([NH2:32])=[O:31])=[N:28][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC.[Cl-].[NH4+]>[Cu]I.C(Cl)Cl.O1CCOCC1>[NH2:22][C:19]1[O:20][CH2:21][C@@:5]2([N:18]=1)[C:4]1[CH:3]=[C:2]([NH:32][C:30]([C:27]3[CH:26]=[CH:25][C:24]([Cl:23])=[CH:29][N:28]=3)=[O:31])[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([O:16][CH3:17])=[CH:9][CH:10]=1

Participants

9

Reactant 5

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 218831585-Chloropyridine-2-carboxamideHCID 584661972'-Bromo-7'-methoxyspiro[1,3-oxazole-4,9'-xanthen]-2-amine

Product 1

HCID 67249958N-((4R)-2-amino-7'-methoxyspiro[1,3-oxazole-4,9'-xanthen]-2'-yl)-5-chloro-2-pyridinecarboxamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A vial was charged with 2′-bromo-7′-methoxyspiro[1,3-oxazole-4,9′-xanthen]-2-amine (90.0 mg, 249 μmol), 5-chloropicolinamide (59 mg, 374 μmol), cesium carbonate (244 mg, 748 μmol), copper(I) iodide (47 mg, 249 μmol), dioxane (2 mL), and N1,N2-dimethylethane-1,2-diamine (27 μl, 249 μmol). The vial was sealed under a blanket of Ar (g) and placed in a 110° C. oil bath for 5 days. The reaction mixture was then poured into a mixture of ammonium chloride solution (10 mL) and DCM (10 mL). The layers were separated, and the aqueous layer was extracted with DCM (2×5 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was dissolved in DMSO and filtered, and the filtrate was purified by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA). The fractions containing the desired product were poured into saturated sodium bicarbonate solution and extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated to give N-((4R)-2-amino-7′-methoxyspiro[1,3-oxazole-4,9′-xanthen]-2′-yl)-5-chloro-2-pyridinecarboxamide as a white solid. MS m/z=437.2 [M+H]+. Calc'd for C22H18ClN4O4: 437.1.

Workup

  1. customplaced in a 110° C.
  2. customfor 5 days
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (2×5 mL)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in DMSO
  9. filtrationfiltered
  10. customthe filtrate was purified by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA)
  11. additionThe fractions containing the desired product
  12. additionwere poured into saturated sodium bicarbonate solution
  13. extractionextracted with DCM (3×)
  14. dry with materialThe combined organic extracts were dried over sodium sulfate
  15. filtrationfiltered
  16. customevaporated

Sources & evidence

ORD record
ord-5984afb1454042dab8a803c07e1cb51d
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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