Diisopropylamine → HCID 67247901, compound

HRID 1970268Notes

Reaction equation

HRID 1970268 reaction equation
I[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](=[N:10][CH:11]=[C:12]([Br:21])[CH:13]=3)[O:8][C:5]2=[CH:6][CH:7]=1.C1COCC1.[CH3:27][C:28]([OH:32])([C:30]#[CH:31])[CH3:29].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)I.C(OCC)(=O)C>[OH:32][C:28]([CH3:29])([CH3:27])[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](=[N:10][CH:11]=[C:12]([Br:21])[CH:13]=3)[O:8][C:5]2=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 8028TetrahydrofuranHCID 82582-Methyl-3-butyn-2-olHCID 58466184HCID 58466184, compound

Product 1

HCID 67247901HCID 67247901, compoundYield 83%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A resealable tube was charged with 7-iodo-3-bromo-spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (0.500 g, 1.092 mmol), tetrakis(triphenylphosphine)palladium (0.126 g, 0.109 mmol) and copper iodide (0.021 g, 0.109 mmol). THF (2.183 mL, 1.092 mmol) was added followed by 2-methylbut-3-yn-2-ol (0.138 g, 1.637 mmol) and diisopropylamine (1.556 mL, 10.92 mmol). The tube was sealed and stirred at RT overnight. The reaction was diluted with water (25 mL) and poured into a separatory funnel containing ethyl acetate (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with 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 7-(3-hydroxy-3-methyl-1-butyn-1-yl)-3-bromo-spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (374 mg, 0.903 mmol, 83% yield) (104420-10-1) as a light yellow foam. MS m/z=414.0 [M+H]+. Calc'd for C19H17BrN3O3: 414.0.

Workup

  1. customThe tube was sealed
  2. additionpoured into a separatory funnel
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×25 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried 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-70a2c44c8e444f829001626363b0d39b
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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