Water → HCID 59272349, compound

HRID 1970275Notes

Reaction equation

HRID 1970275 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](I)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.[CH2:22]1COC[CH2:23]1.[CH3:27][C:28]([OH:32])([C:30]#[CH:31])[CH3:29].C(N[CH:37]([CH3:39])[CH3:38])(C)C.[OH2:40]>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>[NH2:20][C:17]1[O:18][CH2:19][C:15]2([C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:31]#[C:30][C:28]([CH3:29])([OH:32])[CH3:27])[CH:3]=3)[O:8][C:9]3[C:14]2=[CH:13][C:12]([C:22]#[C:23][C:37]([CH3:38])([OH:40])[CH3:39])=[CH:11][CH:10]=3)[N:16]=1

Participants

9

Reactant 5

HCID 962WaterHCID 7912DiisopropylamineHCID 8028TetrahydrofuranHCID 82582-Methyl-3-butyn-2-olHCID 58466184HCID 58466184, compound

Product 1

HCID 59272349HCID 59272349, compoundYield 13.17%

Reagents, catalysts & solvents 3

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

Procedure

A resealable tube was charged with 3-bromo-7-iodo-5′H-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 reaction vessel was sealed and stirred at rt for 12 hours. 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 4,4′-(-2′-aminospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazole]-3,7-diyl)bis(2-methyl-3-butyn-2-ol) (60 mg, 0.144 mmol, 13.17% yield) 104420-10-42 as a yellow film. MS m/z=418.2 [M+H]+. Calc'd for C24H24N3O4: 418.2.

Workup

  1. customThe reaction vessel 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-6fbb6b7f74bf482b865c4026e2cd1180
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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