Tetrahydrofuran → HCID 59272333, compound

HRID 1970249Notes

Reaction equation

HRID 1970249 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:30]=1)[C:18]1[CH:17]=[C:16]([C:19]3[CH:20]=[N:21][CH:22]=[N:23][CH:24]=3)[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([O:25][CH2:26][C:27](=[O:29])[CH3:28])=[CH:9][CH:10]=1.[CH2:31]1COCC1.C[Mg]Cl>CCOCC>[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:30]=1)[C:6]1[CH:7]=[C:8]([O:25][CH2:26][C:27]([CH3:31])([OH:29])[CH3:28])[CH:9]=[CH:10][C:11]=1[O:12][C:13]1[C:18]2=[CH:17][C:16]([C:19]2[CH:24]=[N:23][CH:22]=[N:21][CH:20]=2)=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 67254301HCID 67254301, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 59272333HCID 59272333, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A 15-mL RBF was charged with the product from (S)-1-(2-amino-2′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yloxy)propan-2-one (104 mg, 258 μmol) in THF (2584 μl, 258 μmol). The flask was cooled in an ice-bath for 5 min, and methylmagnesium chloride, (258 μl of a 3.0 M solution in ether, 775 μmol) was added dropwise to it over 20 sec, resulting in a yellowish-white suspension. After 2 h, an additional portion of Grignard reagent (150 uL) was added and the ice-bath was removed. After 2 h, the mixture was quenched with saturated ammonium chloride solution and diluted with EtOAc and water. The layers were separated, and the aqueous layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 40-g Redi-Sep column with 5% MeOH/DCM, then with 8% MeOH/DCM to afford 1-(((4S)-2-amino-7′-(5-pyrimidinyl)spiro[1,3-oxazole-4,9′-xanthen]-2′-yl)oxy)-2-methyl-2-propanol as a white solid. MS m/z=419.2 [M+H]+. Calc'd for C23H23N4O4: 419.2.

Workup

  1. temperatureThe flask was cooled in an ice-bath for 5 min
  2. customresulting in a yellowish-white suspension
  3. customthe ice-bath was removed
  4. waitAfter 2 h
  5. customthe mixture was quenched with saturated ammonium chloride solution
  6. additiondiluted with EtOAc and water
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with EtOAc (2×)
  9. dry with materialThe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by chromatography on a 40-g Redi-Sep column with 5% MeOH/DCM

Sources & evidence

ORD record
ord-fb7fa73f72ba4656b4f07cfcd78cd93d
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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