Ethanolamine → isopropyl ((2S,4R)-1-acetyl-6-(4-((2-hydroxyethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate

HRID 882273Notes

Reaction equation

HRID 882273 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)=[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].[CH2:31]([CH2:33][NH2:34])[OH:32].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:22]=[CH:21][C:17]([C:18](=[O:20])[NH:34][CH2:33][CH2:31][OH:32])=[CH:16][CH:15]=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 700EthanolamineHCID 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 71469254isopropyl ((2S,4R)-1-acetyl-6-(4-((2-hydroxyethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamateYield 80%

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) (116 mg, 0.283 mmol) and ethanolamine (0.034 mL, 0.565 mmol) in DMF (3 mL) were added HATU (161 mg, 0.424 mmol) and DIPEA (0.148 mL, 0.848 mmol). The resulting mixture was stirred at room temperature for 1 h, then water and EtOAc were added. 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-hydroxyethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (102 mg, 80%) as a white solid. LCMS (Formate, 2 min), Rt=0.76 min, MH+=454.

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-e10f7018ee8846d2a86277ecbd508c2c
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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