Dimethylformamide → HCID 67247115, compound

HRID 335754Notes

Reaction equation

HRID 335754 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](N4CCOCC4)[CH:18]=3)[O:13][C:10]2=[CH:11][CH:12]=1)(=O)=O.[CH:34](NC(C)C)(C)[CH3:35].C([CH:43]1[CH2:45][CH2:44]1)#C.C([Sn](CCCC)(CCCC)[C:51]1[CH:56]=[N:55][CH:54]=[CH:53][N:52]=1)CCC.[CH3:65]N(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH3:43][C:45]([CH3:65])([CH3:44])[C:34]#[C:35][C:17]1[CH:18]=[C:19]2[C@:20]3([CH2:24][O:23][C:22]([NH2:25])=[N:21]3)[C:9]3[C:10](=[CH:11][CH:12]=[C:7]([C:51]4[CH:56]=[N:55][CH:54]=[CH:53][N:52]=4)[CH:8]=3)[O:13][C:14]2=[N:15][CH:16]=1

Participants

8

Reactant 5

HCID 6228Dimethylformamide2×HCID 7912DiisopropylamineHCID 138823Cyclopropylacetylene2×HCID 27373162-(Tributylstannyl)pyrazineHCID 86640729HCID 86640729, compound

Product 1

HCID 67247115HCID 67247115, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst2×

Conditions

Temperature
70 °C

Procedure

A vial was charged with (S)-2′-amino-3-morpholino-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-7-yl trifluoromethanesulfonate (0.120 g, 0.247 mmol), tetrakis(triphenylphosphine)palladium (2.85 mg, 2.467 μmol), and copper(i) iodide (4.70 mg, 0.025 mmol). The vial was flushed with Ar (g), then DMF (0.987 mL), diisopropylamine (0.692 mL, 4.93 mmol), and ethynylcyclopropane (0.104 mL, 1.233 mmol) were added in sequence to give a yellow solution. The vial was sealed and heated to 70° C. for two hours at which point 8 mg of tetrakis(triphenylphosphine)palladium and 0.1 mL of cyclopropylacetylene were added and the reaction was heated to 100° C. and stirred for two hours. The vial was purged with Ar (g), then DMF (1.039 mL) and 2-(tributylstannyl)pyrazine (0.197 mL, 0.623 mmol) were added in sequence. The vial was sealed and heated to 110° C. for one hour. The mixture was loaded onto a 2-g SCX-2 column and eluted 4× with methanol to remove impurities. The product was then eluted with 2M ammonia in methanol. The filtrate was evaporated, and the residue was purified via column chromatography (RediSep 40 g, gradient elution 0-5% MeOH:DCM) to afford (S)-3-(3,3-dimethylbut-1-ynyl)-7-(pyrazin-2-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a white solid.

Workup

  1. customThe vial was flushed with Ar (g)
  2. customto give a yellow solution
  3. customThe vial was sealed
  4. additionwere added
  5. temperaturethe reaction was heated to 100° C.
  6. customThe vial was purged with Ar (g)
  7. customThe vial was sealed
  8. temperatureheated to 110° C. for one hour
  9. washeluted 4× with methanol
  10. customto remove impurities
  11. washThe product was then eluted with 2M ammonia in methanol
  12. customThe filtrate was evaporated
  13. customthe residue was purified via column chromatography (RediSep 40 g, gradient elution 0-5% MeOH:DCM)

Sources & evidence

ORD record
ord-83171b92fb7941eb8078b0994bb85904
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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