Formic Acid → CRA-0450 free base

HRID 1373086Notes

Reaction equation

HRID 1373086 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH3:19])[CH:15]=[C:14]2[N:20]1[CH2:25][CH:24]=[C:23]([C:26]#[N:27])[CH2:22][CH2:21]1.Cl.C(O)=[O:30]>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([CH3:19])[CH:15]=[C:14]2[N:20]1[CH2:21][CH:22]=[C:23]([C:26](=[O:30])[NH2:27])[CH2:24][CH2:25]1

Participants

4

Reactant 3

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 225744298-(2,4-Dichlorophenyl)-2-methyl-4-(4-cyano-1,2,3,6-tetrahydropyridin-1-yl)quinoline

Product 1

HCID 9829517CRA-0450 free base

Procedure

In 96% formic acid (5 mL) was dissolved 8-(2,4-dichlorophenyl)-2-methyl-4-(4-cyano-1,2,3,6-tetrahydropyridin-1-yl)quinoline (1.0 g), and hydrogen chloride gas was bubbled into the solution under ice-cooling to saturate the solution therewith. The reaction mixture was stirred at room temperature for 4 hours and then distilled under reduced pressure to remove the solvent. The residue was separated with chloroform and a saturated aqueous sodium hydrogen-carbonate solution, and the organic layer was dried over anhydrous sodium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (silica gel: Wako Gel (C200), eluent: chloroform-methanol=10:1) and then recrystallized from tetrahydrofuran to obtain the title compound (174 mg).

Workup

  1. customwas bubbled into the solution under ice-
  2. temperaturecooling
  3. concentrationto saturate the solution
  4. distillationdistilled under reduced pressure
  5. customto remove the solvent
  6. customThe residue was separated with chloroform
  7. dry with materiala saturated aqueous sodium hydrogen-carbonate solution, and the organic layer was dried over anhydrous sodium sulfate
  8. filtrationThe desiccating agent was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by a silica gel column chromatography (silica gel: Wako Gel (C200), eluent: chloroform-methanol=10:1)
  11. customrecrystallized from tetrahydrofuran

Sources & evidence

ORD record
ord-480d479406ad4de0a2606a52c34c3307
Source dataset
uspto-grants-2007_01
Patent number
US07160900B2

Reaction notes

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