Pyridine → HCID 67427596, compound

HRID 1907803Notes

Reaction equation

HRID 1907803 reaction equation
[CH3:1][C:2]1([CH3:14])[CH2:12][C:5]2[S:6][C:7]([C:9]([OH:11])=O)=[CH:8][C:4]=2[C:3]1=[O:13].[F:15][C:16]1[CH:22]=[CH:21][C:20]([B:23]2[O:27][C:26]([CH3:29])([CH3:28])[C:25]([CH3:31])([CH3:30])[O:24]2)=[CH:19][C:17]=1[NH2:18].N1C=CC=CC=1>C(Cl)Cl>[F:15][C:16]1[CH:22]=[CH:21][C:20]([B:23]2[O:27][C:26]([CH3:28])([CH3:29])[C:25]([CH3:31])([CH3:30])[O:24]2)=[CH:19][C:17]=1[NH:18][C:9]([C:7]1[S:6][C:5]2[CH2:12][C:2]([CH3:1])([CH3:14])[C:3](=[O:13])[C:4]=2[CH:8]=1)=[O:11]

Participants

5

Reactant 3

HCID 1049PyridineHCID 467379902-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 58540128HCID 58540128, compound

Product 1

HCID 67427596HCID 67427596, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 9 (270 mg, 1.29 mmol) and methylene chloride (3 mL). The solution Was cooled to 0° C., and 15 (172 mg, 1.29 mmol) was added dropwise. After this addition was complete, the reaction was warmed to room temperature and stirred for 2 h. 14 (305 mg, 1.29 mmol) was then added. After this addition, the reaction was cooled to 0° C., and anhydrous pyridine (306 mg, 3.87 mmol) was added. The cooling bath was removed, and the reaction mixture was stirred at room temperature for 16 h. After this time, the solvents were removed under reduced pressure, and the resulting residue was partitioned between water (10 mL) and methylene chloride (20 mL). The layers were separated, and the aqueous phase was extracted with methylene chloride (2×10 mL). The organic extracts were combined and dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford 27 in 45% yield (235 mg) as a white solid: mp 88-89° C.; 1H NMR (500 MHz, CDCl3) δ 8.73 (d, J=8.5 Hz), 7.87 (s, 1H), 7.62 (s, 1H), 7.56 (t, 1H, J=6.5 Hz), 7.14 (dd, 1H, J=11.0, 8.5 Hz), 3.11 (s, 2H) 1.38 (s, 12H), 1.33 (s, 6H); MS (APCI+) m/z 430.3 (M+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. additionAfter this addition
  4. temperaturethe reaction was warmed to room temperature
  5. additionAfter this addition
  6. temperaturethe reaction was cooled to 0° C.
  7. customThe cooling bath was removed
  8. stirringthe reaction mixture was stirred at room temperature for 16 h
  9. customAfter this time, the solvents were removed under reduced pressure
  10. customthe resulting residue was partitioned between water (10 mL) and methylene chloride (20 mL)
  11. customThe layers were separated
  12. extractionthe aqueous phase was extracted with methylene chloride (2×10 mL)
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-bcef8f3d05b8482da057374323222efb
Source dataset
uspto-grants-2013_12
Patent number
US08598174B2

Reaction notes

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