(Diethylamino)sulfur trifluoride → HCID 59026712, compound

HRID 606114Notes

Reaction equation

HRID 606114 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:28]O)[N:14]([CH2:15][C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH:17]=3)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.C(N(S(F)(F)[F:36])CC)C>ClCCl>[F:36][CH2:28][C:13]1[N:14]([CH2:15][C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH:17]=2)[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:1])[C:11]=2[N:12]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 59026688HCID 59026688, compound

Product 1

HCID 59026712HCID 59026712, compoundYield 42.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

The methods described in Examples 30 and 31 were repeated on a larger scale to provide (4-amino-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-2-yl)methanol. The reaction described in Example 31 was heated at reflux and was complete within three hours. Under a nitrogen atmosphere, a suspension of (4-amino-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-2-yl)methanol (2.31 g, 5.93 mmol) in dichloromethane (100 mL) was cooled to −78° C. (Diethylamino)sulfur trifluoride (DAST) (0.95 mL, 7.2 mmol) was added dropwise. The mixture was stirred for 30 minutes at −78° C. and then was allowed to warm to room temperature slowly and stirred for one hour. The reaction mixture was diluted with dichloromethane and washed with saturated aqueous potassium carbonate. Additional dichloromethane and water were added to dissolve solids. The aqueous layer was separated and extracted with dichloromethane. The combined organic fractions were washed sequentially with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 3% to 5% CMA in chloroform) followed by recrystallization from acetonitrile. The crystals were dried under high vacuum for 18 hours at 90° C. to provide 0.994 g of 2-(fluoromethyl)-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine as tan crystals, mp 192.0-193.0° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux
  3. additionwas added dropwise
  4. temperatureto warm to room temperature slowly
  5. stirringstirred for one hour
  6. washwashed with saturated aqueous potassium carbonate
  7. additionAdditional dichloromethane and water were added
  8. dissolutionto dissolve solids
  9. customThe aqueous layer was separated
  10. extractionextracted with dichloromethane
  11. washThe combined organic fractions were washed sequentially with water and brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe crude product was purified by column chromatography on silica gel (eluting with 3% to 5% CMA in chloroform)
  16. customfollowed by recrystallization from acetonitrile
  17. customThe crystals were dried under high vacuum for 18 hours at 90° C.

Sources & evidence

ORD record
ord-8f21a1e8bebe4f31be1f5a05baef846f
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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