Diisopropylethylamine → 1-methylethyl {(2S,4R)-1-acetyl-6-[4-(2-{[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]amino}-2-oxoethyl)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate

HRID 882244Notes

Reaction equation

HRID 882244 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21](O)=[O:22])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:24][C:25]([O:27][CH:28]([CH3:30])[CH3:29])=[O:26])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2].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.[NH2:65][CH2:66][CH2:67][NH:68][C:69](=[O:75])[O:70][C:71]([CH3:74])([CH3:73])[CH3:72]>CN(C=O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([NH:65][CH2:66][CH2:67][NH:68][C:69]([O:70][C:71]([CH3:72])([CH3:74])[CH3:73])=[O:75])=[O:22])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:24][C:25](=[O:26])[O:27][CH:28]([CH3:29])[CH3:30])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 187201N-BOC-ethylenediamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 529352352-(4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)acetic acid

Product 1

HCID 867094181-methylethyl {(2S,4R)-1-acetyl-6-[4-(2-{[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]amino}-2-oxoethyl)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamateYield 49.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a flask charged with 2-(4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)acetic acid (for a preparation see Intermediate 50) (85 mg, 0.2 mmol) and HATU (91 mg, 0.240 mmol) was added DMF (2 mL) and the mixture treated with DIPEA (0.105 mL, 0.600 mmol) at room temperature. After 5 min, 1,1-dimethylethyl (2-aminoethyl)carbamate (0.047 mL, 0.300 mmol) was added, the mixture was stirred at room temperature for 3 h and then partitioned between EtOAc and water. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. the residue was purified by chromatography, eluting with a MeOH/DCM gradient, to give 1-methylethyl {(2S,4R)-1-acetyl-6-[4-(2-{[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]amino}-2-oxoethyl)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (56 mg, 0.099 mmol, 49.4% yield) as a pale yellow foam. LCMS (Formate, 2 min), Rt=0.91 min, MH+=455.

Workup

  1. custompartitioned between EtOAc and water
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with EtOAc
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe residue was purified by chromatography
  9. washeluting with a MeOH/DCM gradient

Sources & evidence

ORD record
ord-47afdb15054c426baeb3ee1a77de4f06
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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