Dimethylformamide → HCID 58466256, compound

HRID 1970361Notes

Reaction equation

HRID 1970361 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].C(NC(C)C)(C)C>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.C(OCC)(=O)C>[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

9

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 135123,3-Dimethyl-1-butyneHCID 58466302HCID 58466302, compound

Product 1

HCID 58466256HCID 58466256, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Combined 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). Added DMF (6903 μL, 1.381 mmol), 3,3-dimethylbut-1-yne (340 mg, 4.14 mmol) and diisopropylamine (4837 μL, 34.5 mmol), flushed with argon, sealed and heated at 90° C. for 2 hours. The reaction was diluted with water (100 mL) and poured into a separatory funnel containing ethyl acetate (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (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. customsealed
  2. additionpoured into a separatory funnel
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with water
  6. dry with materialbrine, dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a brown oil that
  10. 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-44496f9b443948abbc10be630548592a
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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