Triethylamine → HCID 131728658, compound

HRID 1363033Notes

Reaction equation

HRID 1363033 reaction equation
[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:15][CH:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])[CH2:18][CH2:17]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.[CH3:34][CH:35]([S:37]([Cl:40])(=[O:39])=[O:38])[CH3:36]>C(Cl)Cl>[ClH:40].[ClH:40].[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:15][CH:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][CH2:25][NH:26][S:37]([CH:35]([CH3:36])[CH3:34])(=[O:39])=[O:38])[CH2:18][CH2:17]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 824082-Propanesulfonyl chloride2×HCID 57926053HCID 57926053, compound2×

Product 1

HCID 131728658HCID 131728658, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(4-{4-[(6-Butyl-8-quinolinyl)oxy]-1-piperidinyl}butyl)amine (for example, as prepared for Intermediate 37) (87 mg, 0.24 mmol) was dissolved in DCM (2 ml), and treated with triethylamine (167 μl, 1.2 mmol), and 2-propanesulfonyl chloride (commercially available, for example, from Aldrich) (54 μl, 0.48 mmol). The mixture was stirred at room temperature for 1.5 h. LCMS analysis indicated that reaction was not complete. Further triethylamine (167 μl, 1.2 mmol), and 2-propanesulfonyl chloride (54 μl, 0.48 mmol) were added and the mixture stirred at room temperature for 1 h. The reaction was quenched by the addition of methanol then concentrated under a stream of nitrogen. The residue was re-dissolved in methanol and applied to an SCX-2 cartridge (20 g) eluting with methanol, followed by 10% aqueous 0.88 s.g. ammonia in methanol. The relevant fractions were concentrated, and the residue was purified by MDAP. The appropriate fractions were combined and concentrated, but the product was found to contain impurities, thought to be (3-{4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinyl}propyl)sulfamic acid. The material was dissolved in methanol and applied to an aminopropyl cartridge (5 g) eluting with methanol. The relevant fractions were combined and concentrated to give the title compound as the free base (43 mg, 39%): LCMS RT=2.63 min, ES+ve m/z 462 (M+H)+. Approximately half the material was dissolved in methanol and treated with 1.25 M hydrogen chloride in methanol (1 ml, excess). The volatiles were removed under a stream of nitrogen to give the title compound (26 mg): LCMS RT=2.70 min, ES+ve m/z 462 (M+H)+.

Workup

  1. customLCMS analysis indicated that reaction
  2. stirringthe mixture stirred at room temperature for 1 h
  3. customThe reaction was quenched by the addition of methanol
  4. concentrationthen concentrated under a stream of nitrogen
  5. dissolutionThe residue was re-dissolved in methanol
  6. washeluting with methanol
  7. customfollowed by 10% aqueous 0.88 s
  8. concentrationThe relevant fractions were concentrated
  9. customthe residue was purified by MDAP
  10. concentrationconcentrated
  11. dissolutionThe material was dissolved in methanol
  12. washeluting with methanol
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-b750647e09264f8985c98077c4cc1a22
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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