2,6-Lutidine → Biphenyl-2-ylcarbamic Acid 1-[2-({3-[3-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]-amino}ethyl)phenylcarbamoyl]propyl}methylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 2412252Notes

Reaction equation

HRID 2412252 reaction equation
[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16]CN(CCC(O)=O)C[CH2:12]1)=[O:9].CCN=[C:31]=[N:32][CH2:33][CH2:34][CH2:35][N:36]([CH3:38])[CH3:37].Cl.[OH:40]N1C2N=CC=CC=2N=N1.[CH2:50]([N:57]([CH2:74][C@@H:75]([C:84]1[CH:93]=[CH:92][C:91]([O:94][CH2:95][C:96]2[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=2)=[C:90]2[C:85]=1[CH:86]=[CH:87][C:88](=[O:102])[NH:89]2)[O:76][Si:77]([C:80]([CH3:83])([CH3:82])[CH3:81])([CH3:79])[CH3:78])[CH2:58][CH2:59][C:60]1[CH:61]=[C:62]([NH:66][C:67](=[O:73])[CH2:68][CH2:69][CH2:70]NC)[CH:63]=[CH:64][CH:65]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.N1C(C)=CC=CC=1C>CN(C=O)C.C(Cl)Cl.O>[CH2:50]([N:57]([CH2:74][C@@H:75]([C:84]1[CH:93]=[CH:92][C:91]([O:94][CH2:95][C:96]2[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=2)=[C:90]2[C:85]=1[CH:86]=[CH:87][C:88](=[O:102])[NH:89]2)[O:76][Si:77]([C:80]([CH3:83])([CH3:82])[CH3:81])([CH3:79])[CH3:78])[CH2:58][CH2:59][C:60]1[CH:61]=[C:62]([NH:66][C:67]([CH2:68][CH2:69][CH2:70][N:32]([CH3:31])[C:33]([CH2:34][CH2:35][N:36]2[CH2:37][CH2:12][CH:11]([O:10][C:8](=[O:9])[NH:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=3[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:16][CH2:38]2)=[O:40])=[O:73])[CH:63]=[CH:64][CH:65]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

Participants

9

Reactant 5

HCID 79372,6-LutidineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 218806073-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic AcidHCID 66782297N-[3-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]amino}ethyl)phenyl]-4-methylaminobutyramide

Product 1

HCID 86704960Biphenyl-2-ylcarbamic Acid 1-[2-({3-[3-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]-amino}ethyl)phenylcarbamoyl]propyl}methylcarbamoyl)ethyl]piperidin-4-yl EsterYield 72%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]-propionic acid (127 mg, 0.344 mmol) and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (69.0 mg, 0.360 mmol) in DMF (5 mL) at room temperature was added a solution of 1-hydroxy-7-azabenzotriazole in DMF (0.5 M, 0.720 mL, 0.360 mmol). N-[3-(2-{Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]amino}ethyl)phenyl]-4-methylaminobutyramide (240 mg, 0.327 mmol) and 2,6-lutidine (114 μL, 0.982 mmol) were added and the resulting mixture was stirred overnight. LC-MS (Method 2-90) showed product was present (Rt 4.13 min; m/z 1083.7 [M+]). Water was added and this mixture was diluted with DCM. The layers were separated and the organic layer was washed with aqueous 10% lithium chloride solution (2×), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-20% MeOH in DCM with 1% TEA) to give the title compound (258 mg, 72% yield) as a yellow oil.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with aqueous 10% lithium chloride solution (2×)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography (0-20% MeOH in DCM with 1% TEA)

Sources & evidence

ORD record
ord-2a0024c9ec684cdd8d3e1c508b2c2901
Source dataset
uspto-grants-2014_08
Patent number
US08816088B2

Reaction notes

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