1,2,3,4-Tetrahydroquinoline → HCID 10309434, compound

HRID 1182131Notes

Reaction equation

HRID 1182131 reaction equation
Br[CH2:2][CH2:3][CH2:4][N:5]=[C:6]=[O:7].[NH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1.C(N(C(C)C)CC)(C)C.Cl.[F:28][C:29]1[CH:39]=[CH:38][C:32]([O:33][CH:34]2[CH2:37][NH:36][CH2:35]2)=[CH:31][CH:30]=1>C(#N)C>[F:28][C:29]1[CH:39]=[CH:38][C:32]([O:33][CH:34]2[CH2:35][N:36]([CH2:2][CH2:3][CH2:4][NH:5][C:6]([N:8]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH2:11][CH2:10][CH2:9]3)=[O:7])[CH2:37]2)=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 694601,2,3,4-TetrahydroquinolineHCID 81531Diisopropylethylamine2×HCID 5445441-Bromo-3-isocyanatopropaneHCID 214287323-(4-Fluorophenoxy)azetidine hydrochloride

Product 1

HCID 10309434HCID 10309434, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 1-Bromo-3-isocyanato-propane (0.164 g, 1.0 mmol) in acetonitrile is stirred with 1,2,3,4-Tetrahydro-quinoline (0.133 g, 1.0 mmol) and diisopropylethylamine (0.2 ml, 1.2 mmol). The reaction mixture is stirred for 2 hours at ambient temperature and then the solvent removed. The crude product is taken-up in acetonitrile (4 ml) and diisopropylethylamine (0.2 ml, 1.2 mmol) and 3-(4-Fluoro-phenoxy)-azetidine hydrochloride (0.11 g, 1.0 mmol) added. The reaction mixture is stirred at ambient temperature for 18 hours, the solvent evaporated and the crude partitioned between ethylacetate and saturated sodium bicarbonate solution. The organic phase is washed with brine, dried over magnesium sulphate and evaporated. The crude product is purified by flash silica chromatography (elution gradient ethylacetate then 5:95 methanol/dichloromethane) to afford 3,4-Dihydro-2H-quinoline-1-carboxylic acid {3-[3-(4-fluoro-phenoxy)-azetidin-1-yl]-propyl}-amide. [MH]+ 444.2

Workup

  1. customthe solvent removed
  2. stirringThe reaction mixture is stirred at ambient temperature for 18 hours
  3. customthe solvent evaporated
  4. customthe crude partitioned between ethylacetate and saturated sodium bicarbonate solution
  5. washThe organic phase is washed with brine
  6. dry with materialdried over magnesium sulphate
  7. customevaporated
  8. customThe crude product is purified by flash silica chromatography (
  9. washelution gradient ethylacetate

Sources & evidence

ORD record
ord-b8aa396d715c40809992771e43b4cffc
Source dataset
uspto-grants-2007_10
Patent number
US07288537B2

Reaction notes

Loading…