1,4-Dioxane → (S)-2'-(neopentyloxy)-7'-(pyrazin-2-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 1970286Notes

Reaction equation

HRID 1970286 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][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:9][CH:10]=3)[C@:5]3([CH2:25][O:24][C:23]([NH2:26])=[N:22]3)[C:4]=2[CH:3]=1.C([Sn](CCCC)(CCCC)[C:32]1[CH:37]=[N:36][CH:35]=[CH:34][N:33]=1)CCC.O1CCOCC1>CO.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>[CH2:17]([O:16][C:8]1[CH:9]=[CH:10][C:11]2[O:12][C:13]3[C:4](=[CH:3][C:2]([C:32]4[CH:37]=[N:36][CH:35]=[CH:34][N:33]=4)=[CH:15][CH:14]=3)[C@@:5]3([CH2:25][O:24][C:23]([NH2:26])=[N:22]3)[C:6]=2[CH:7]=1)[C:18]([CH3:19])([CH3:21])[CH3:20]

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 27373162-(Tributylstannyl)pyrazineHCID 58466128(R)-2'-bromo-7'-(neopentyloxy)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Product 1

HCID 58466155(S)-2'-(neopentyloxy)-7'-(pyrazin-2-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

A vial was charged with (R)-2′-bromo-7′-(neopentyloxy)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (55.6 mg, 0.133 mmol), tetrakis(triphenylphosphine)palladium (0) (15.40 mg, 0.013 mmol), 2-(tributylstannyl)pyrazine (148 mg, 0.400 mmol), and dioxane (0.7 mL). The vial was sealed under a blanket of Ar gas and placed in a 100° C. oil for 16 h. The mixture was then cooled and filtered through celite. The filtrate was evaporated, and the residue was purified by chromatography on a 12-g Redi-Sep column, eluting with 0-10% MeOH/DCM to give a brown oil. This oil was dissolved in MeOH and filtered through a 2 micron filter, then purified further by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA). The product containing fractions were combined in saturated aqueous sodium bicarbonate solution with the aid of MeOH. The mixture was extracted with DCM (2×), and the combined organic extracts were dried over sodium sulfate, filtered, and evaporated to give (S)-2′-(neopentyloxy)-7′-(pyrazin-2-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as a white solid. MS m/z=417.2 [M+H]+. Calc'd for C24H25N4O3: 417.19.

Workup

  1. customThe vial was sealed under a blanket of Ar gas
  2. customplaced in a 100° C.
  3. customfor 16 h
  4. temperatureThe mixture was then cooled
  5. filtrationfiltered through celite
  6. customThe filtrate was evaporated
  7. customthe residue was purified by chromatography on a 12-g Redi-Sep column
  8. washeluting with 0-10% MeOH/DCM
  9. customto give a brown oil
  10. filtrationfiltered through a 2 micron
  11. filtrationfilter
  12. custompurified further by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA)
  13. additionThe product containing fractions
  14. extractionThe mixture was extracted with DCM (2×)
  15. dry with materialthe combined organic extracts were dried over sodium sulfate
  16. filtrationfiltered
  17. customevaporated

Sources & evidence

ORD record
ord-a3b5f01f029b4e749d84acdc42a27a41
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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