Dimethylformamide → HCID 67242282, compound

HRID 335760Notes

Reaction equation

HRID 335760 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). 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). (DCM was used because this product is partially soluble in water and EtOAc is not as good a solvent for it). 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-6322f167073d4427af9f6ef4460764e5
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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