Benzyl {6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}(4-{[N-({[(2S)-1'-{2-[(5R)-3-[3,5-bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)-N-methyl-beta-alanyl](methyl)amino}phenyl)carbamate → 1-{2-[{6-[(4-{[N-({[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)-N-methyl-beta-alanyl](methyl)amino}phenyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate

HRID 446613Notes

Reaction equation

HRID 446613 reaction equation
[C:1]1([C:101]2[CH:106]=[CH:105][CH:104]=[CH:103][CH:102]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][N:19]([CH3:100])[C:20](=[O:99])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]([C:37]2[CH:42]=[CH:41][C:40]([N:43]([C:45](=[O:98])[CH2:46][CH2:47][N:48]([C:50](=[O:97])[CH2:51][O:52][C@@H:53]3[C:61]4([CH2:66][CH2:65][N:64]([CH2:67][CH2:68][C@:69]5([C:90]6[CH:95]=[CH:94][C:93]([F:96])=[CH:92][CH:91]=6)[O:73][CH2:72][N:71]([C:74](=[O:89])[C:75]6[CH:80]=[C:79]([C:81]([F:84])([F:83])[F:82])[CH:78]=[C:77]([C:85]([F:88])([F:87])[F:86])[CH:76]=6)[CH2:70]5)[CH2:63][CH2:62]4)[C:60]4[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=4)[CH2:54]3)[CH3:49])[CH3:44])=[CH:39][CH:38]=2)C(=O)OCC2C=CC=CC=2)[CH2:13][CH2:12]1)=[O:9]>C(O)C.C(OCC)(=O)C.[C].[Pd]>[C:1]1([C:101]2[CH:102]=[CH:103][CH:104]=[CH:105][CH:106]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:9])[O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][N:19]([C:20](=[O:99])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:37]2[CH:38]=[CH:39][C:40]([N:43]([C:45](=[O:98])[CH2:46][CH2:47][N:48]([C:50](=[O:97])[CH2:51][O:52][C@@H:53]3[C:61]4([CH2:66][CH2:65][N:64]([CH2:67][CH2:68][C@:69]5([C:90]6[CH:95]=[CH:94][C:93]([F:96])=[CH:92][CH:91]=6)[O:73][CH2:72][N:71]([C:74](=[O:89])[C:75]6[CH:80]=[C:79]([C:81]([F:82])([F:83])[F:84])[CH:78]=[C:77]([C:85]([F:87])([F:88])[F:86])[CH:76]=6)[CH2:70]5)[CH2:63][CH2:62]4)[C:60]4[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=4)[CH2:54]3)[CH3:49])[CH3:44])=[CH:41][CH:42]=2)[CH3:100])[CH2:13][CH2:12]1

Participants

5

Reactant 1

HCID 86663479Benzyl {6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}(4-{[N-({[(2S)-1'-{2-[(5R)-3-[3,5-bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)-N-methyl-beta-alanyl](methyl)amino}phenyl)carbamate

Product 1

HCID 867619211-{2-[{6-[(4-{[N-({[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)-N-methyl-beta-alanyl](methyl)amino}phenyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamateYield 88.1%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

The compound (180 mg, 0.12 mmol) obtained in Example 97f was dissolved in a mixed solvent of ethanol (3 mL) and ethyl acetate (3 mL), 10% palladium-carbon (36 mg, 20% by weight) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 18 hours. After the reaction was completed, the reaction mixture was filtered through celite, the filtrate was washed with methanol, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol, 30:1, v/v) to give the title compound (141 mg; yield, 86%) as a white solid.

Workup

  1. additionwas added
  2. filtrationthe reaction mixture was filtered through celite
  3. washthe filtrate was washed with methanol
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by NH silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-c17ffaa0fa5b44fb8252057e642e87f3
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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