Potassium Carbonate → HCID 53464881, compound

HRID 335919Notes

Reaction equation

HRID 335919 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C@@:20]3([CH2:24][O:23][C:22]([NH2:25])=[N:21]3)[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:26]#[C:27][C:28]4([CH3:32])[CH2:31][O:30][CH2:29]4)[CH:18]=3)[O:13][C:10]2=[CH:11][CH:12]=1)(=O)=O.[C:35]([C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1)#[N:36].C(=O)([O-])[O-].[K+].[K+]>>[NH2:25][C:22]1[O:23][CH2:24][C@:20]2([C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:26]#[C:27][C:28]4([CH3:32])[CH2:31][O:30][CH2:29]4)[CH:18]=3)[O:13][C:10]3[C:9]2=[CH:8][C:7]([C:41]2[CH:42]=[C:37]([CH:38]=[CH:39][CH:40]=2)[C:35]#[N:36])=[CH:12][CH:11]=3)[N:21]=1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 86640736HCID 86640736, compound

Product 1

HCID 53464881HCID 53464881, compound

Procedure

A vial was charged with (S)-2′-amino-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-7-yl trifluoromethanesulfonate (92 mg, 0.186 mmol, prepared from the alcohol as described in Method CC6), 3-cyanophenylboronic acid (82 mg, 0.557 mmol), potassium carbonate (128 mg, 0.928 mmol), and Cl2Pd(dppf) (1.516 mg, 1.857 μmol). The vial was flushed with argon, then dioxane (928 μL) and water (0.5 mL) were added. The vial was sealed and placed in an 80° C. oil bath for 1.5 hours. An additional portion of catalyst (3 mg) was added and the mixture was returned to the 80° C. oil bath. Heating was continued for an additional 2 hours. The mixture was cooled to rt and was diluted with EtOAc (15 mL) and brine (20 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (15 mL). The combined organic layers were dried over sodium sulfate, filtered, and evaporated. The residue was chromatographed on a 40-g Redi-Sep column, eluting with 0-50% of a 90:10:1 mix of CH2Cl2/MeOH/NH4OH in CH2Cl2 to give (S)-3-(2′-amino-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-7-yl)benzonitrile as a pale, tan solid.

Workup

  1. customThe vial was flushed with argon
  2. additiondioxane (928 μL) and water (0.5 mL) were added
  3. customThe vial was sealed
  4. customplaced in an 80° C.
  5. customfor 1.5 hours
  6. additionAn additional portion of catalyst (3 mg) was added
  7. customwas returned to the 80° C. oil bath
  8. temperatureHeating
  9. additionwas diluted with EtOAc (15 mL) and brine (20 mL)
  10. customThe layers were separated
  11. extractionthe aqueous layer was extracted with EtOAc (15 mL)
  12. dry with materialThe combined organic layers were dried over sodium sulfate
  13. filtrationfiltered
  14. customevaporated
  15. customThe residue was chromatographed on a 40-g Redi-Sep column
  16. washeluting with 0-50% of a 90:10:1
  17. additionmix of CH2Cl2/MeOH/NH4OH in CH2Cl2

Sources & evidence

ORD record
ord-89ffbe58de73471087bc7d5b5affcb82
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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