Dimethylformamide → (S)-2'-amino-3-(3,6-dihydro-2H-pyran-4-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

HRID 335736Notes

Reaction equation

HRID 335736 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17](Br)[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([OH:21])=[CH:10][CH:11]=3)[N:6]=1.C(=O)([O-])[O-].[K+].[K+].[O:28]1[CH2:33][CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH2:30][CH2:29]1.CN(C=O)C>O>[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:31]4[CH2:32][CH2:33][O:28][CH2:29][CH:30]=4)[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([OH:21])=[CH:10][CH:11]=3)[N:6]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 58466114(S)-2'-amino-3-bromo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

Product 1

HCID 67241212(S)-2'-amino-3-(3,6-dihydro-2H-pyran-4-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A vial was charged with (S)-2′-amino-3-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol (380 mg, 1.091 mmol), potassium carbonate (754 mg, 5.46 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (688 mg, 3.27 mmol), pd(ph3p)4 (126 mg, 0.109 mmol), DMF (5457 μL), and water (2.5 mL). The vial was sealed, placed in 80° C. and heated overnight. The mixture was diluted with water (35 mL) and extracted with EtOAc (3×15 mL). The combined organic extract was dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 80-g Redi-Sep column, eluting with 0-100% of a 90:10:1 mix of DCM/MeOH/NH4OH in DCM to give (S)-2′-amino-3-(3,6-dihydro-2H-pyran-4-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol as an orange solid.

Workup

  1. customThe vial was sealed
  2. customplaced in 80° C.
  3. temperatureheated overnight
  4. extractionextracted with EtOAc (3×15 mL)
  5. extractionThe combined organic extract
  6. dry with materialwas dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by chromatography on a 80-g Redi-Sep column
  10. washeluting with 0-100% of a 90:10:1
  11. additionmix of DCM/MeOH/NH4OH in DCM

Sources & evidence

ORD record
ord-7d96c3d508fc49d4948c3ad0fd374216
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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