Tetramethyltin → HCID 59272336, compound

HRID 1970387Notes

Reaction equation

HRID 1970387 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:32]=1)[C:18]1[C:17](Br)=[C:16]([O:20][CH2:21][C:22]([CH3:25])([OH:24])[CH3:23])[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)=[CH:9][CH:10]=1.[CH3:33][Sn](C)(C)C>O.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>[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:32]=1)[C:18]1[C:17]([CH3:33])=[C:16]([O:20][CH2:21][C:22]([CH3:25])([OH:24])[CH3:23])[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 11661TetramethyltinHCID 59272391HCID 59272391, compound

Product 1

HCID 59272336HCID 59272336, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A vial was charged with (S)-1-(2-amino-1′-bromo-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-2′-yloxy)-2-methylpropan-2-ol (150 mg, 0.302 mmol), tetrakis(triphenylphosphine)palladium(0) (34.9 mg, 0.030 mmol), TEA (168 μL, 1.209 mmol), and tetramethyltin (617 μL, 4.53 mmol). The vial was sealed and heated in a 90° C. oil bath 16 h. The mixture was cooled to RT, diluted with water, and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was dissolved in methanol and filtered through a 0.2 micron filter. The filtrate was purified by reverse-phase HPLC (10-40% CH3CN/H2O with 0.1% TFA). The fractions containing product combined in saturated aq. sodium bicarbonate solution with the aid of methanol and extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated to give (S)-1-(2-amino-1′-methyl-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-2′-yloxy)-2-methylpropan-2-ol as a white solid. MS m/z=432.0. Calc'd for C25H26N3O4: 432.19.

Workup

  1. customThe vial was sealed
  2. temperatureThe mixture was cooled to RT
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was dissolved in methanol
  8. filtrationfiltered through a 0.2 micron
  9. filtrationfilter
  10. customThe filtrate was purified by reverse-phase HPLC (10-40% CH3CN/H2O with 0.1% TFA)
  11. additionThe fractions containing product
  12. extractionextracted with DCM (3×)
  13. dry with materialThe combined organic extracts were dried over sodium sulfate
  14. filtrationfiltered
  15. customevaporated

Sources & evidence

ORD record
ord-5f9837f29f7144d9a4524a64167a6d50
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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