Hydrochloric Acid → HCID 68629730, compound

HRID 1931509Notes

Reaction equation

HRID 1931509 reaction equation
[C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:21]#N)[CH:17]=3)[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([Mg]Br)=[CH:26][CH:25]=1.Cl.[OH-:33].[Na+]>O1CCCC1>[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:21]([C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[N:12]=[C:11]([NH:10][C@H:1]2[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH2:3][CH2:2]2)[CH:20]=[CH:19]3)=[O:33])=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68630708HCID 68630708, compoundHCID 178418676HCID 178418676, compound

Product 1

HCID 68629730HCID 68629730, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (ice bath) and stirred suspension of 2-((R)-indan-1-ylamino)-quinoline-6-carbonitrile (example 53, step B) (230 mg, 0.81 mmol) in tetrahydrofurane (4 ml) was added drop wise a 1M solution of 4-fluorophenyl-magnesium bromide (2.4 ml, 2.43 mmol), the reaction mixture was heated under reflux conditions for 20 h and poured into ice-water (20 ml). 2N hydrochloride solution (5 ml) was added, the mixture was stirred at room temperature for 10 min, 3 N sodium hydroxide solution (5 ml) was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with brine (2×50 ml), dried (MgSO4) and evaporated. The crude product was purified by flash chromatography (ethyl acetate/heptane) on silica gel to yield (4-fluoro-phenyl)-[2-((R)-indan-1-ylamino)-quinolin-6-yl]-methanone as light yellow foam (220 mg, 71%). MS: m/e=383.2 (M+H+).

Workup

  1. temperatureTo a cooled (ice bath)
  2. temperaturethe reaction mixture was heated under reflux conditions for 20 h
  3. stirringthe mixture was stirred at room temperature for 10 min
  4. extractionthe mixture was extracted with ethyl acetate (3×100 ml)
  5. washThe combined organic layers were washed with brine (2×50 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe crude product was purified by flash chromatography (ethyl acetate/heptane) on silica gel

Sources & evidence

ORD record
ord-4adbfbfb367240bfa7481e1d88f943ce
Source dataset
uspto-grants-2012_05
Patent number
US08188284B2

Reaction notes

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