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

HRID 1970243ノート

反応式

HRID 1970243 の反応式
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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-5984afb1454042dab8a803c07e1cb51d
出典データセット
uspto-grants-2013_04
特許番号
US08426447B2

反応ノート

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