Methanol → HCID 59026688, compound

HRID 606113Notes

Reaction equation

HRID 606113 reaction equation
C([O:3][CH2:4][C:5]1[N:6]([CH2:19][C:20]2[O:24][N:23]=[C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:21]=2)[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[C:9]([NH2:17])[C:8]=2[N:18]=1)C.B(Br)(Br)Br.CO>ClCCCl.ClCCl>[NH2:17][C:9]1[C:8]2[N:18]=[C:5]([CH2:4][OH:3])[N:6]([CH2:19][C:20]3[O:24][N:23]=[C:22]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[CH:21]=3)[C:7]=2[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:10]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 25134Boron tribromide2×HCID 59026704HCID 59026704, compound

Product 1

HCID 59026688HCID 59026688, compoundYield 17.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

Under a nitrogen atmosphere, a solution of 2-(ethoxymethyl)-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine (0.9923 g, 2.377 mmol) in 1,2-dichloroethane (55 mL) was cooled to about 0° C., and boron tribromide (5.9 mL of a 1 M solution in dichloromethane) was added dropwise. After the reaction was stirred cold for 30 minutes, it was heated at 50° C. for six hours. An analysis by HPLC indicated the reaction was incomplete, and the reaction was again cooled to about 0° C., and additional boron tribromide (1.5 mL) was added dropwise. After the reaction was stirred cold for ten minutes, it was heated at 50° C. for 16 hours. Methanol (30 mL) was added, and the reaction mixture was allowed to cool to room temperature. After 16 hours, the precipitate from the reaction was isolated by filtration and washed sequentially with aqueous potassium hydroxide (30 mL of 1 N), methanol (15 mL), and diethyl ether (15 mL). The solid was then triturated with boiling acetonitrile and isolated by hot filtration to provide 0.161 g of (4-amino-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-2-yl)methanol as a white powder, mp 262.0-263.0° C.

Workup

  1. temperaturethe reaction was again cooled to about 0° C.
  2. stirringAfter the reaction was stirred cold for ten minutes
  3. temperatureit was heated at 50° C. for 16 hours
  4. temperatureto cool to room temperature
  5. waitAfter 16 hours
  6. customthe precipitate from the reaction was isolated by filtration
  7. washwashed sequentially with aqueous potassium hydroxide (30 mL of 1 N), methanol (15 mL), and diethyl ether (15 mL)
  8. customThe solid was then triturated with boiling acetonitrile
  9. customisolated by hot filtration

Sources & evidence

ORD record
ord-30a0f8bafd004dc98b4ee1d0d91a069c
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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