N,N-Dimethylethylenediamine → isopropyl ((2S,4R)-1-acetyl-6-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate

HRID 882272Notes

Reaction equation

HRID 882272 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](O)=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25])[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2].[CH3:31][N:32]([CH3:36])[CH2:33][CH2:34][NH2:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[CH:16][C:17]([C:18](=[O:19])[NH:35][CH2:34][CH2:33][N:32]([CH3:36])[CH3:31])=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24](=[O:25])[O:26][CH:27]([CH3:29])[CH3:28])[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 66053N,N-DimethylethylenediamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67193625HCID 67193625, compound

Product 1

HCID 71469251isopropyl ((2S,4R)-1-acetyl-6-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamateYield 41%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (for a preparation see Intermediate 48) (67 mg, 0.163 mmol) and N1,N1-dimethylethane-1,2-diamine (28.8 mg, 0.326 mmol) in DMF (2 mL) were added HATU (93 mg, 0.245 mmol) and DIPEA (0.086 mL, 0.490 mmol). The resulting mixture was stirred at room temperature for 1 h, then hydrolyzed by adding water and EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (×3). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was dissolved in 1:1 MeOH/DMSO and was purified by MDAP (formate). The appropriate fractions were combined and concentrated under reduced pressure to give isopropyl ((2S,4R)-1-acetyl-6-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (35 mg, 41%) as a viscous colourless oil. LCMS (Formate, 2 min), Rt=0.65 min, MH+=481.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous phase was extracted with EtOAc (×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in 1:1 MeOH/DMSO
  8. customwas purified by MDAP (formate)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-df430b9010664cc1a969277f6dfa6326
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

Loading…