1,1'-Carbonyldiimidazole → benzyl (S)-2-((R)-3-((S)-1-(benzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclopentylpropylmethylcarbamate

HRID 1254376Notes

Reaction equation

HRID 1254376 reaction equation
[CH2:1]([O:8][C:9](=[O:21])[N:10]([CH2:12][CH:13]([NH2:20])[CH2:14][CH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N=CN([C:27]([N:29]2[CH:33]=N[CH:31]=[CH:30]2)=[O:28])C=1.CCN(C(C)C)C(C)C.[O:43]1[C:47]2[C:48]([C@:52]([C@@H:60]3CCCN[CH2:61]3)([OH:59])[CH2:53][CH2:54][CH2:55][CH2:56][O:57][CH3:58])=[CH:49][CH:50]=[CH:51][C:46]=2[CH:45]=[CH:44]1>C(Cl)Cl>[O:43]1[C:47]2[C:48]([C@:52]([C@@H:60]3[CH2:61][CH2:31][CH2:30][N:29]([C:27]([NH:20][C@@H:13]([CH2:14][CH:15]4[CH2:16][CH2:17][CH2:18][CH2:19]4)[CH2:12][N:10]([CH3:11])[C:9](=[O:21])[O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:28])[CH2:33]3)([OH:59])[CH2:53][CH2:54][CH2:55][CH2:56][O:57][CH3:58])=[CH:49][CH:50]=[CH:51][C:46]=2[CH:45]=[CH:44]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 59382903(S)-1-(benzofuran-7-yl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-olHCID 67189318HCID 67189318, compound

Product 1

HCID 57544782benzyl (S)-2-((R)-3-((S)-1-(benzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclopentylpropylmethylcarbamateYield 51.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2-amino-3-cyclopentyl-propyl)-methyl-carbamic acid benzyl ester (87 mg, 0.3 mmol) and CDI (48.6 mg, 0.3 mmol) in CH2Cl2 (5 mL) cooled to 0-5° C. was added DIEA (0.5 mL). After stirring for 30 minutes, a solution of (S)-1-(benzofuran-7-yl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (95.1 mg, 0.3 mmol) in CH2Cl2 (3 mL) was added dropwise. The reaction mixture was allowed to warm to rt and stirred overnight. The mixture was washed with water (10 mL). The aqueous layer was extracted with CH2Cl2 (2×15 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by prep HPLC to give benzyl (S)-2-((R)-3-((S)-1-(benzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclopentylpropylmethylcarbamate (98.5 mg, 51.9%).

Workup

  1. stirringstirred overnight
  2. washThe mixture was washed with water (10 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (2×15 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-af1c064241c14c639b89ea56adcdfe40
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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