Triethylamine → HCID 131728657, compound

HRID 1363027Notes

Reaction equation

HRID 1363027 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][NH2:25])[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.[CH3:33][CH:34]([S:36]([Cl:39])(=[O:38])=[O:37])[CH3:35]>C(Cl)Cl.CO>[ClH:39].[ClH:39].[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][NH:25][S:36]([CH:34]([CH3:35])[CH3:33])(=[O:38])=[O:37])[CH2:18][CH2:17]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 8471Triethylamine3×HCID 824082-Propanesulfonyl chloride3×HCID 66921928HCID 66921928, compound2×

Product 1

HCID 131728657HCID 131728657, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(3-{4-[(6-Butyl-8-quinolinyl)oxy]-1-piperidinyl}propyl)amine (for example, as prepared for Intermediate 36) (30 mg, 0.09 mmol) was dissolved in DCM (1 ml), and treated with triethylamine (38 μl, 0.27 mmol), and 2-propanesulfonyl chloride (commercially available, for example, from Aldrich) (20 μl, 0.18 mmol). The mixture was stirred in a stoppered vial at room temperature for 1 h, then left to stand at room temperature overnight. LCMS analysis indicated that reaction was not complete. Further triethylamine (38 μl, 0.27 mmol), and 2-propanesulfonyl chloride (17 μl, 0.18 mmol) were added and the mixture stirred at room temperature for 1.5 h. LCMS analysis indicated that reaction was still not complete. Further triethylamine (19 μl, 0.14 mmol), and 2-propanesulfonyl chloride (10 μl, 0.09 mmol) were added and the mixture stirred at room temperature overnight. The mixture was diluted with methanol and applied to an SCX-2 cartridge (5 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 an impurity, 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: LCMS RT=2.68 min, ES+ve m/z 448 (M+H)+. The material was dissolved in methanol and treated with 1.25 M hydrogen chloride in methanol (0.5 ml, excess). The volatiles were removed under a stream of nitrogen to give the title compound (13 mg, 27%): LCMS RT=2.80 min, ES+ve m/z 448 (M+H)+.

Workup

  1. waitleft
  2. waitto stand at room temperature overnight
  3. customLCMS analysis indicated that reaction
  4. stirringthe mixture stirred at room temperature for 1.5 h
  5. customLCMS analysis indicated that reaction
  6. stirringthe mixture stirred at room temperature overnight
  7. washeluting with methanol
  8. customfollowed by 10% aqueous 0.88 s
  9. concentrationThe relevant fractions were concentrated
  10. customthe residue was purified by MDAP
  11. concentrationconcentrated
  12. dissolutionThe material was dissolved in methanol
  13. washeluting with methanol
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-772452d3a7b5446da3856d19161c780f
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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