2-(Dimethylamino)ethanol → 2-(Dimethylamino)ethyl 4-((2S,4R)-1-acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate hydrochloride

HRID 572353Notes

Reaction equation

HRID 572353 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2].C1CCC(N=C=NC2CCCCC2)CC1.[CH3:47][N:48]([CH3:52])[CH2:49][CH2:50]O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[ClH:30].[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([O:20][CH2:50][CH2:49][N:48]([CH3:52])[CH3:47])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=2)[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 79022-(Dimethylamino)ethanolHCID 10868DicyclohexylcarbodiimideHCID 529122224-[(2s,4r)-1-Acetyl-4-[(4-Chlorophenyl)amino]-2-Methyl-1,2,3,4-Tetrahydroquinolin-6-Yl]benzoic Acid

Product 1

HCID 899551572-(Dimethylamino)ethyl 4-((2S,4R)-1-acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate hydrochloride

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

4-{(2S,4R)-1-Acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzoic acid (for a preparation see Intermediate 18 ((100 mg, 0.230 mmol) was suspended in DCM (1 mL). DMAP (33.7 mg, 0.276 mmol) and DCC (52.2 mg, 0.253 mmol) were added and the mixture was stirred for 5 min producing a clear yellow solution. 2-(Dimethylamino)ethanol (20.5 mg, 0.230 mmol) in DCM (0.5 mL) was subsequently added and the reaction stirred at room temperature overnight. The reaction was diluted with DCM (8.5 ml) and washed with NaOH (2N), water and brine (10 ml each) then dried with Na2SO4, filtered and concentrated in vacuo to yield an off-white semi-solid. The crude product dissolved in a minimal volume of DCM (with a few drops of MeOH to aid solubility) and applied to a 25 g cartridge. The cartridge was dried under vacuum at 40° C. for 1 h then eluted with 1% 2M NH3 in methanol/DCM for 2 CV then 1-5% 2M NH3 in methanol in DCM over 10 CV then held at 5% for 5 CV. The appropriate fractions were concentrated in vacuo to yield the free amine product (18.8 mg) as a clear oil. The latter was taken up in the minimum of DCM and HCl in Et2O (1N, 0.19 mL, 0.190 mmol) added and the solvent evaporated under a stream of nitrogen. A small amount of Et2O was added (˜1 mL) and evaporated under nitrogen to yield 2-(dimethylamino)ethyl 4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzoate hydrochloride (76.7 mg, 0.135 mmol, 58.6% yield) as a white solid. LCMS (Formate, 2 min), Rt=0.91 min, MH+=506.

Workup

  1. customproducing a clear yellow solution
  2. stirringthe reaction stirred at room temperature overnight
  3. washwashed with NaOH (2N), water and brine (10 ml each)
  4. dry with materialthen dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto yield an off-white semi-solid
  8. customThe cartridge was dried under vacuum at 40° C. for 1 h
  9. washthen eluted with 1% 2M NH3 in methanol/DCM for 2 CV
  10. concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-da3d21ed79454d75be1e86f85fb571a8
Source dataset
uspto-grants-2015_05
Patent number
US09029395B2

Reaction notes

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