Dimethylformamide → (S)-2'-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

HRID 1970337Notes

Reaction equation

HRID 1970337 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.CN(C=O)C.C(NC(C)C)(C)C.[CH3:34][C:35]([OH:39])([C:37]#[CH:38])[CH3:36]>O.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:38]#[C:37][C:35]([OH:39])([CH3:36])[CH3:34])[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

8

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 82582-Methyl-3-butyn-2-olHCID 58466114(S)-2'-amino-3-bromo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

Product 1

HCID 67240963(S)-2'-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A 25-mL flask was charged with (S)-2′-amino-3-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol (1.012 g, 2.91 mmol), copper(i) iodide (0.055 g, 0.291 mmol), and tetrakis(triphenylphosphine)palladium (0.034 g, 0.029 mmol). The vial was flushed with Ar(g), then a septum was attached. DMF (5.81 mL), diisopropylamine (6.11 mL, 43.6 mmol), and 2-methylbut-3-yn-2-ol (1.137 mL, 11.63 mmol) were added in sequence to give a clear, brown solution. A reflux condenser was attached, and the flask was placed in a 75° C. oil bath for 4 hours. The mixture was diluted with water (35 mL) and extracted with DCM (4×20 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue, which contained a considerable amount of DMF, was loaded onto a 10-g SCX-2 column with the aid of methanol. The column was eluted with methanol to remove impurities, then with 2M ammonia in methanol to elute the product. The filtrate was evaporated, and the residue was chromatographed on an 80-g Redi-Sep column, eluting with 0-10% MeOH/DCM to give (S)-2′-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol.

Workup

  1. customThe vial was flushed with Ar(g)
  2. customto give a clear, brown solution
  3. customA reflux condenser was attached
  4. customwas placed in a 75° C.
  5. customfor 4 hours
  6. extractionextracted with DCM (4×20 mL)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. washThe column was eluted with methanol
  11. customto remove impurities
  12. washwith 2M ammonia in methanol to elute the product
  13. customThe filtrate was evaporated
  14. customthe residue was chromatographed on an 80-g Redi-Sep column
  15. washeluting with 0-10% MeOH/DCM

Sources & evidence

ORD record
ord-b09d46c172204a68906d52a5158e7d04
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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