Hydrochloric Acid → (Rac)-2'-(3,3-dimethylbut-1-ynyl)-7'-(pyrimidin-5-yl)-5h-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 335693Notes

Reaction equation

HRID 335693 reaction equation
Cl[C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([C:16]4[CH:17]=[N:18][CH:19]=[N:20][CH:21]=4)=[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(=O)([O-])[O-].[Cs+].[Cs+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C1CCN2C(=NCCC2)CC1.[CH3:62][C:63]([CH3:67])([CH3:66])[C:64]#[CH:65].Cl.[OH-].[NH4+]>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[CH3:62][C:63]([CH3:67])([CH3:66])[C:64]#[C:65][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([C:16]4[CH:17]=[N:18][CH:19]=[N:20][CH:21]=4)=[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

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 135123,3-Dimethyl-1-butyneHCID 14923Ammonium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 452561062'-Chloro-7'-(5-pyrimidinyl)spiro[1,3-oxazole-4,9'-xanthen]-2-amine

Product 1

HCID 58466325(Rac)-2'-(3,3-dimethylbut-1-ynyl)-7'-(pyrimidin-5-yl)-5h-spiro[oxazole-4,9'-xanthen]-2-amineYield 49%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
150 °C

Procedure

A microwave vial was charged with (racemic)-2′-Chloro-7′-(5-pyrimidinyl)spiro[1,3-oxazole-4,9′-xanthen]-2-amine (100 mg, 274 μmol), cesium carbonate (134 mg, 411 μmol), bis(triphenylphosphine)palladium(II) chloride (19 mg, 27 μmol) and tri-tert-butylphosphonium tetrafluoroborate (16 mg, 55 DMF (1 ml), DBU (21 μl, 137 μmol) and 3,3-dimethylbut-1-yne (167 μl, 1371 μmol) were added. The vial was sealed and heated at 150° C. in Biotage microwave oven for 60 min. The mixture was diluted with 5 ml of EtOAc, filtered through Celite and concentrated in vacuo to give brown oil, which was re-dissolved in 7 ml of EtOAc and shaken with 10 ml of 2N HCl. Acidic aqueous layer was basified with 30% ammonium hydroxide and precipitated brown oil was extracted twice with EtOAc. The organic layers were washed with brine, concentrated, dissolved in 1.5 ml of DMF, filtered through Nalgene PTFE 0.2 mkm filter and subjected to preparative reverse phase HPLC (15-90% ACN in 0.1% aq TFA). The fractions containing product were concentrated in vacuo in order to remove ACN, saturated NaHCO3 was added and the mixture was extracted with EtOAc (15 ml). The organic layer was washed with brine, dried over MgSO4 and concentrated to give (rac)-2′-(3,3-dimethylbut-1-ynyl)-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (49% yield).

Workup

  1. additionwere added
  2. customThe vial was sealed
  3. filtrationfiltered through Celite
  4. concentrationconcentrated in vacuo
  5. customto give brown oil, which
  6. customprecipitated brown oil
  7. extractionwas extracted twice with EtOAc
  8. washThe organic layers were washed with brine
  9. concentrationconcentrated
  10. dissolutiondissolved in 1.5 ml of DMF
  11. filtrationfiltered through Nalgene PTFE 0.2 mkm
  12. filtrationfilter
  13. additionThe fractions containing product
  14. concentrationwere concentrated in vacuo in order
  15. customto remove ACN, saturated NaHCO3
  16. additionwas added
  17. extractionthe mixture was extracted with EtOAc (15 ml)
  18. washThe organic layer was washed with brine
  19. dry with materialdried over MgSO4
  20. concentrationconcentrated

Sources & evidence

ORD record
ord-7b441a7fac9b413182fdb883cd7e2576
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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