Dimethylformamide → HCID 58466256, compound

HRID 335767Notes

Reaction equation

HRID 335767 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:21][CH3:22])[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.CN(C=O)C.[CH3:28][C:29]([CH3:33])([CH3:32])[C:30]#[CH:31]>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>[CH3:28][C:29]([CH3:33])([CH3:32])[C:30]#[C:31][C:2]1[CH:3]=[C:4]2[C:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:21][CH3:22])[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 135123,3-Dimethyl-1-butyneHCID 58466302HCID 58466302, compound

Product 1

HCID 58466256HCID 58466256, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

3-Bromo-7-methoxy-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (104186-10-peak 1) (500 mg, 1.381 mmol), tetrakis(triphenylphosphine)palladium (160 mg, 0.138 mmol), copper(i) iodide (52.6 mg, 0.276 mmol) were combined, and to the mixture was added DMF (6903 μL, 1.381 mmol), 3,3-dimethylbut-1-yne (340 mg, 4.14 mmol) and DIPA (4837 μL, 34.5 mmol). The reaction was flushed with argon, sealed and heated at 90° C. for 2 hours. The reaction mixture was diluted with water (100 mL) and poured into a separatory funnel containing EtOAc (100 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water and then brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown oil that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide the desired product contaminated with triphenylphosphine. The yellow solid was suspended in 25 mL of ether, resulting in the formation of a fine white precipitate. Decanted ether and washed the solid with 10 mL of ether. Dried under reduced pressure to provide 3-(3,3-dimethylbut-1-ynyl)-7-methoxy-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a white solid.

Workup

  1. customThe reaction was flushed with argon
  2. customsealed
  3. additionThe reaction mixture was diluted with water (100 mL)
  4. additionpoured into a separatory funnel
  5. additioncontaining EtOAc (100 mL)
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
  8. washThe combined organic layers were washed with water
  9. dry with materialbrine, dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto provide a brown oil that
  13. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-31b21769cc6c45e796b8f8f31fd42730
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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