Tetrahydrofuran → HCID 67246795, compound

HRID 1970270Notes

Reaction equation

HRID 1970270 reaction equation
[CH3:1][O:2][C:3]([CH3:27])([CH3:26])[C:4]#[C:5][C:6]1[CH:7]=[C:8]2[C:19]3([CH2:23][O:22][C:21]([NH2:24])=[N:20]3)[C:18]3[C:13](=[N:14][CH:15]=[C:16](Br)[CH:17]=3)[O:12][C:9]2=[CH:10][CH:11]=1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=1.C1COCC1.C(=O)([O-])[O-].[K+].[K+]>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>[CH3:1][O:2][C:3]([CH3:27])([CH3:26])[C:4]#[C:5][C:6]1[CH:7]=[C:8]2[C:19]3([CH2:23][O:22][C:21]([NH2:24])=[N:20]3)[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:30]4[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=4)[CH:17]=3)[O:12][C:9]2=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 67247760HCID 67247760, compound

Product 1

HCID 67246795HCID 67246795, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

7-(3-Methoxy-3-methyl-1-butyn-1-yl)-3-bromo-spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (300 mg, 0.700 mmol), tetrakis(triphenylphosphine)palladium (81 mg, 0.070 mmol), 3-pyridineboronic acid (172 mg, 1.401 mmol) and THF (7005 μL, 0.700 mmol) were combined in a sealable tube. Potassium carbonate (1.5 M) (1401 μL, 2.101 mmol) was added to the tube, which was then flushed with argon, sealed and heated at 110° C. for 1.5 hours. The reaction was diluted with water (50 mL) and poured into a separatory funnel containing ethyl acetate (25 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-methoxy-3-methyl-1-butyn-1-yl)-3-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (235 mg, 0.551 mmol, 79% yield) as a light yellow solid. MS m/z=427.2 [M+H]+. Calc'd for C25H23N4O3: 427.2.

Workup

  1. customwas then flushed with argon
  2. customsealed
  3. additionThe reaction was diluted with water (50 mL)
  4. additionpoured into a separatory funnel
  5. additioncontaining ethyl acetate (25 mL)
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×25 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried 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-ad50f7cb063d4adf90e118e87b09b537
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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