1-Bromo-2-methylpropane → 2'-Iso-butyloxy-7'-(5-pyrimidinyl)spiro[1,3-oxazole-4,9'-xanthen]-2-amine

HRID 1970240Notes

Reaction equation

HRID 1970240 reaction equation
[OH:1][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+].[CH2:33](Br)[CH:34]([CH3:36])[CH3:35]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[CH2:33]([O:1][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)[CH:34]([CH3:36])[CH3:35]

Participants

6

Reactant 3

HCID 65551-Bromo-2-methylpropane2×HCID 10796Cesium carbonate2×HCID 584661412'-Hydroxy-7'-(5-pyrimidinyl)spiro[1,3-oxazole-4,9'-xanthen]-2-amine

Product 1

HCID 452559162'-Iso-butyloxy-7'-(5-pyrimidinyl)spiro[1,3-oxazole-4,9'-xanthen]-2-amine

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A glass vial was charged with 2′-hydroxy-7′-(5-pyrimidinyl)spiro[1,3-oxazole-4,9′-xanthen]-2-amine (prepared as described in Example 3; 41.60 mg, 120 μmol), tetrabutylammonium iodide (8.85 mg, 24.0 μmol), cesium carbonate (58.6 mg, 180 mol), DMF (0.48 mL), and isobutyl bromide (16.3 μl, 150 μmol). The vial was sealed and placed in a 90° C. oil bath for 15 h. Additional portions of cesium carbonate (40 mg) and isobutyl bromide (16 uL) were added, and the vial was heated in a Biotage Initiator microwave reactor for 1.5 h at 100° C. The mixture was then partitioned between EtOAc (10 mL) and water (20 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on silica gel (eluting with 0-80% of a 90:10:1 DCM/MeOH/NH4OH solution in DCM) to give 2′-iso-butyloxy-7′-(5-pyrimidinyl)spiro[1,3-oxazole-4,9′-xanthen]-2-amine as an oily tan solid. MS m/z=403.2 [M+H]+. Calc'd for C23H23N4O3: 403.2.

Workup

  1. customThe vial was sealed
  2. customplaced in a 90° C.
  3. customfor 15 h
  4. customThe mixture was then partitioned between EtOAc (10 mL) and water (20 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×10 mL)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by chromatography on silica gel (eluting with 0-80% of a 90:10:1 DCM/MeOH/NH4OH solution in DCM)

Sources & evidence

ORD record
ord-3a45286210d74c9a886a949e02b88933
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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