Dimethylformamide → HCID 67242282, compound

HRID 335757Notes

Reaction equation

HRID 335757 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.C1COCC1.CN(C=O)C.C(NC(C)C)(C)C.[CH3:39][C:40]([OH:44])([C:42]#[CH:43])[CH3:41]>O.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.[Cu]I>[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:43]#[C:42][C:40]([OH:44])([CH3:41])[CH3:39])[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

9

Reactant 5

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 8028TetrahydrofuranHCID 82582-Methyl-3-butyn-2-olHCID 58466194(4′R)-2′-Amino-3-bromospiro[5H-[1]benzopyrano[2,3-b]pyridine-5,4′(5′H)-oxazol]-7-ol

Product 1

HCID 67242282HCID 67242282, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
85 °C

Procedure

Combined (R)-2′-amino-3-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol (2.259 g, 6.49 mmol), tetrakis(triphenylphosphine)palladium (0.750 g, 0.649 mmol), copper(i) iodide (0.124 g, 0.649 mmol) and THF (26.0 mL, 6.49 mmol) and DMF (26.0 mL, 6.49 mmol) in a reaction tube. Added diisopropylamine (18.19 mL, 130 mmol) then 2-methylbut-3-yn-2-ol (3.17 mL, 32.4 mmol) and flushed the reaction tube with argon. Sealed and heated at 85° C. for 3 hours. The mixture was diluted with water (100 mL) and extracted with DCM (1×100 mL, 2×50 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The resuling liquid was poured onto a 25-g SCX-2 column and eluted with methanol. The product was then eluted with 2M ammonia in methanol. The filtrate was evaporated and purified by chromatography on a 120-g Redi-Sep column, eluting with 0-100% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM to give (R)-2′-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol as a tan solid.

Workup

  1. customSealed
  2. extractionextracted with DCM (1×100 mL, 2×50 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. additionThe resuling liquid was poured onto a 25-g SCX-2 column
  7. washeluted with methanol
  8. washThe product was then eluted with 2M ammonia in methanol
  9. customThe filtrate was evaporated
  10. custompurified by chromatography on a 120-g Redi-Sep column
  11. washeluting with 0-100% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM

Sources & evidence

ORD record
ord-a9269d46ede34ff0b9c3b175a4ebd8b4
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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