Cesium carbonate → HCID 59272376, compound

HRID 1970287Notes

Reaction equation

HRID 1970287 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:26]=1)[C:18]1[CH:17]=[C:16]([OH:19])[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([C:20]2[CH:21]=[N:22][CH:23]=[N:24][CH:25]=2)=[CH:9][CH:10]=1.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[CH2:39][CH:40]1[CH2:44][CH2:43][O:42][CH2:41]1)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>CN(C=O)C.CCOC(C)=O>[N:22]1[CH:21]=[C:20]([C:8]2[CH:9]=[CH:10][C:11]3[O:12][C:13]4[C:18](=[CH:17][C:16]([O:19][CH2:39][CH:40]5[CH2:44][CH2:43][O:42][CH2:41]5)=[CH:15][CH:14]=4)[C@:5]4([CH2:4][O:3][C:2]([NH2:1])=[N:26]4)[C:6]=3[CH:7]=2)[CH:25]=[N:24][CH:23]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2758875Trifluoromethanesulfonate2×HCID 216645293-Tetrahydrofuranylmethyl triflateHCID 59272383HCID 59272383, compound

Product 1

HCID 59272376HCID 59272376, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-Amino-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (0.075 g, 0.217 mmol) and cesium carbonate (0.106 g, 0.325 mmol) were dissolved in DMF (0.7 mL) and stirred for five minutes before being cooled in an ice bath. (Tetrahydrofuran-3-yl)methyl trifluoromethanesulfonate (0.056 g, 0.238 mmol) was dissolved in DMF (0.15 mL) and added dropwise to the reaction, which was stirred for one hour. An additional equivalent of triflate was added and the reaction was stirred for five days. The reaction was cooled to 0° C. and 0.5 eq. of triflate was dissolved in 0.1 mL of DMF and added dropwise to the reaction. The reaction was stirred for two days. The reaction was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep 40 g, gradient elution 0-10% MeOH:DCM) but the material was impure so the material was repurified via Gilson HPLC (10-90% MeCN:H2O). The product fractions were partitioned between DCM and saturated sodium bicarbonate solution. The aqueous layer was extracted with DCM, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated to afford (S)-2′-(pyrimidin-5-yl)-7′-((tetrahydrofuran-3-yl)methoxy)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as a white solid. LC-MS MH+ 431.4

Workup

  1. temperaturebefore being cooled in an ice bath
  2. additionadded dropwise to the reaction, which
  3. stirringwas stirred for one hour
  4. stirringthe reaction was stirred for five days
  5. additionadded dropwise to the reaction
  6. stirringThe reaction was stirred for two days
  7. washwashed with water
  8. extractionThe aqueous layer was extracted with EtOAc
  9. washthe combined organic layers were washed with brine
  10. dry with materialdried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe material was purified via column chromatography (RediSep 40 g, gradient elution 0-10% MeOH:DCM)
  14. customwas repurified via Gilson HPLC (10-90% MeCN:H2O)
  15. customThe product fractions were partitioned between DCM and saturated sodium bicarbonate solution
  16. extractionThe aqueous layer was extracted with DCM
  17. dry with materialthe combined organic layers were dried with sodium sulfate
  18. filtrationfiltered
  19. concentrationconcentrated

Sources & evidence

ORD record
ord-784834e8211b4deb890ca7ccb484f5a3
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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