Triethylamine → 1-{2-[{6-[(4-{[4-({[(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)piperazin-1-yl]carbonyl}phenyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate

HRID 446598Notes

Reaction equation

HRID 446598 reaction equation
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH2:37][C:38]([OH:40])=[O:39])[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[C:64]1([C:106]2[CH:111]=[CH:110][CH:109]=[CH:108][CH:107]=2)[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=1[NH:70][C:71](=[O:105])[O:72][CH:73]1[CH2:78][CH2:77][N:76]([CH2:79][CH2:80][N:81]([CH3:104])[C:82](=[O:103])[CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][NH:88][C:89]2[CH:94]=[CH:93][C:92]([C:95]([N:97]3[CH2:102][CH2:101][NH:100][CH2:99][CH2:98]3)=[O:96])=[CH:91][CH:90]=2)[CH2:75][CH2:74]1>C(Cl)Cl>[CH:38]([O-:40])=[O:39].[NH4+:8].[C:64]1([C:106]2[CH:111]=[CH:110][CH:109]=[CH:108][CH:107]=2)[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=1[NH:70][C:71](=[O:105])[O:72][CH:73]1[CH2:74][CH2:75][N:76]([CH2:79][CH2:80][N:81]([C:82](=[O:103])[CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][NH:88][C:89]2[CH:94]=[CH:93][C:92]([C:95]([N:97]3[CH2:98][CH2:99][N:100]([C:38](=[O:39])[CH2:37][O:36][C@@H:28]4[C:25]5([CH2:26][CH2:27][N:22]([CH2:21][CH2:20][C@:11]6([C:13]7[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=7)[O:10][CH2:9][N:8]([C:6](=[O:7])[C:5]7[CH:41]=[C:42]([C:44]([F:45])([F:46])[F:47])[CH:43]=[C:3]([C:2]([F:49])([F:1])[F:48])[CH:4]=7)[CH2:12]6)[CH2:23][CH2:24]5)[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[CH2:29]4)[CH2:101][CH2:102]3)=[O:96])=[CH:91][CH:90]=2)[CH3:104])[CH2:77][CH2:78]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 666714801-{2-[Methyl(6-{[4-(piperazin-1-ylcarbonyl)phenyl]amino}hexanoyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamateHCID 86663420HCID 86663420, compound

Product 2

HCID 2723923Ammonium formateYield 0.1%HCID 870995651-{2-[{6-[(4-{[4-({[(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)piperazin-1-yl]carbonyl}phenyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamateYield 126.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The compound (74 mg, 0.106 mmol) obtained in Example 1j was dissolved in methylene chloride (1.5 mL), triethylamine (17 μL., 0.121 mmol) and pivaloyl chloride (13 μL, 0.105 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 25 minutes. A solution of the compound (66 mg, 0.101 mmol) obtained in Example 92b in methylene chloride (1.5 mL) was added dropwise to the reaction mixture under ice cooling, and the mixture was stirred at room temperature for 2.5 days. The solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→40:1, v/v) and further by reverse phase preparative column chromatography (Waters; XTerra Prep MS C18 OBD, 5 μm, 30×100 mm) (acetonitrile:0.1% aqueous ammonium formate solution=60:40, v/v) to give the title compound (89 mg; yield, 66%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 2.5 days
  2. customThe solvent was evaporated under reduced pressure
  3. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→40:1, v/v) and further by reverse phase preparative column chromatography (Waters; XTerra Prep MS C18 OBD, 5 μm, 30×100 mm) (acetonitrile

Sources & evidence

ORD record
ord-6570b8e178e547609c4152c095e9e6b8
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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