Dimethylformamide → (S)-4-(2'-amino-7-(cyclopropylethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yl)-2-methylbut-3-yn-2-ol

HRID 1970355Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1970355
FC(F)(S(O[C:17]1[CH:18]=[C:19]2[C@@:30]3([CH2:34][O:33][C:32]([NH2:35])=[N:31]3)[C:29]3[C:24](=[N:25][CH:26]=[C:27]([C:36]#[C:37][C:38]([OH:41])([CH3:40])[CH3:39])[CH:28]=3)[O:23][C:20]2=[CH:21][CH:22]=1)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.CN(C=O)C.C(NC(C)C)(C)C.[C:55]([CH:57]1[CH2:59][CH2:58]1)#[CH:56]>O.[Cu]I>[NH2:35][C:32]1[O:33][CH2:34][C@:30]2([C:29]3[C:24](=[N:25][CH:26]=[C:27]([C:36]#[C:37][C:38]([CH3:40])([OH:41])[CH3:39])[CH:28]=3)[O:23][C:20]3[C:19]2=[CH:18][C:17]([C:56]#[C:55][CH:57]2[CH2:59][CH2:58]2)=[CH:22][CH:21]=3)[N:31]=1

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 138823CyclopropylacetyleneHCID 86640731(S)-2'-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-7-yl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate

Produkt 1

HCID 58466154(S)-4-(2'-amino-7-(cyclopropylethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yl)-2-methylbut-3-yn-2-ol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A 0.5-2 mL vial was charged with (S)-2′-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-7-yl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate (106 mg, 0.167 mmol), and copper(i) iodide (3.19 mg, 0.017 mmol). The vial was flushed with Ar (g), then DMF (669 μL, 0.167 mmol), diisopropylamine (469 μL, 3.35 mmol), and ethynylcyclopropane (70.8 μL, 0.836 mmol) were added in sequence to give a yellow solution. The vial was sealed and heated overnight in at 80° C. The mixture was diluted with water (15 mL) and extracted with EtOAc (3×10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 40-g Redi-Sep column, eluting with 0-50% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM to give (S)-4-(2′-amino-7-(cyclopropylethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-3-yl)-2-methylbut-3-yn-2-ol as a tan solid after evaporation from DCM/hexanes.

Aufarbeitung

  1. customThe vial was flushed with Ar (g)
  2. customto give a yellow solution
  3. customThe vial was sealed
  4. extractionextracted with EtOAc (3×10 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by chromatography on a 40-g Redi-Sep column
  10. washeluting with 0-50% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM

Quellen und Nachweise

ORD-Eintrag
ord-395b4cebd5e645c887e626b900e020f8
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08426447B2

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