Chloroform → 6-Fluoro-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol

HRID 1095758Notes

Reaction equation

HRID 1095758 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:12][Si](C(C)C)(C(C)C)C(C)C)[CH:11]=1)[N:8]=[C:7]([CH:23]=[CH:24]OC)[CH:6]=[CH:5]2.BrN1C(=O)CCC1=O.[CH3:35][O:36][CH2:37][CH2:38][O:39][C:40]1[CH:45]=[CH:44][N:43]=[C:42]([NH2:46])[CH:41]=1.C(Cl)(Cl)Cl>C1COCC1.O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([OH:12])[CH:11]=1)[N:8]=[C:7]([C:23]1[N:43]3[CH:44]=[CH:45][C:40]([O:39][CH2:38][CH2:37][O:36][CH3:35])=[CH:41][C:42]3=[N:46][CH:24]=1)[CH:6]=[CH:5]2

Participants

8

Reactant 4

HCID 6212ChloroformHCID 67184N-bromobutanimideHCID 667815966-Fluoro-2-(2-methoxyvinyl)-8-(triisopropylsilyloxy)quinolineHCID 667820424-(2-Methoxyethoxy)pyridin-2-amine

Product 1

HCID 583692626-Fluoro-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

6-Fluoro-2-(2-methoxyvinyl)-8-(triisopropylsilyloxy)quinoline (2.5 g, 6.6 mmol) was dissolved in THF (10.3 mL) and water (2.6 mL) and cooled to 0° C. The solution was treated dropwise with a solution of freshly recrystallized N-bromosuccinimide (1.24 g, 6.99 mmol) dissolved in THF (7 mL) and water (1.75 mL). The reaction was stirred at 0° C. for 20 minutes then warmed and stirred at ambient temperature for 2.5 hours. The reaction was treated with 4-(2-methoxyethoxy)pyridin-2-amine (1.12 g, 6.65 mmol) and the mixture was heated to reflux overnight. The mixture was cooled and solids formed in the flask. Chloroform (50 mL), ethyl acetate (300 mL), and water (50 mL) were added to disperse the solids and the undissolved solids were collected by filtration and washed with ethyl acetate and water, then air-dried, (1.2 g). MS APCI (+) m/z 354.1 (M+1) detected.

Workup

  1. temperaturethen warmed
  2. stirringstirred at ambient temperature for 2.5 hours
  3. temperaturethe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureThe mixture was cooled
  6. customsolids formed in the flask
  7. additionto disperse the solids
  8. filtrationthe undissolved solids were collected by filtration
  9. washwashed with ethyl acetate and water
  10. customair-dried

Sources & evidence

ORD record
ord-4715ac6fd20a479c8cd96e6355192d41
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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