Triethylamine → 4-{[N-((1R)-1-Carbamoyl-3 methyl-butyl)-N-(4-chlorobenzenesulfonyl)amino]-methyl}-piperidine-1-carboxylic acid phenethylamide

HRID 1893842Notes

Reaction equation

HRID 1893842 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C@H:19]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:20]([NH2:22])=[O:21])[CH2:12][CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CCN(CC)CC.[N:34]([CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[C:35]=[O:36].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:37]([NH:34][C:35]([N:16]1[CH2:15][CH2:14][CH:13]([CH2:12][N:11]([C@@H:19]([C:20](=[O:21])[NH2:22])[CH2:23][CH:24]([CH3:26])[CH3:25])[S:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)(=[O:9])=[O:10])[CH2:18][CH2:17]1)=[O:36])[CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 160602Phenethyl isocyanateHCID 516892Sodium BicarbonateHCID 59001103(2R)-2-[N-(4-Chlorobenzenesulfonyl)-N-(piperidin-4-ylmethyl)amino]-4-methyl-pentanoic acid amide

Product 1

HCID 590010804-{[N-((1R)-1-Carbamoyl-3 methyl-butyl)-N-(4-chlorobenzenesulfonyl)amino]-methyl}-piperidine-1-carboxylic acid phenethylamideYield 55.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2R)-2-[N-(4-chlorobenzenesulfonyl)-N-(piperidin-4-ylmethyl)amino]-4-methyl-pentanoic acid amide (Example 126, 0.10 g, 0.22 mmol) and Et3N (32 μL, 0.25 mmol) in CH2Cl2 (3.0 mL) was added (2-isocyanato-ethyl)-benzene (0.040 mL, 0.30 mmol). The reaction was stirred at rt for 18 h and then was poured into sat. aq. NaHCO3 and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, and concentrated to an oily residue. The residue was further purified on a BIOTAGE® system (eluted with 75% EtOAc/hexanes) to afford the desired product as a white solid (67 mg, 52%). MS (ESI), (M+H)+549.00; 1H NMR (CDCl3, 500 MHz) δ 7.71 (d, 2H, J=8.6), 7.71 (d, 2H, J=8.9), 7.15-7.35 (m, 5H), 6.64 (s, 1H), 5.86 (s, 1H), 4.15 (dd, 1H, J=5.2, 9.5), 3.88 (d, 1H, J=13), 3.76 (d, 1H, J=13), 3.46 (t, 2H, J=6.7), 3.21-3.29 (m, 1H), 2.97 (dd, 1H, J=4.6, 14), 2.65-2.85 (m, 4H), 1.75-1.95 (m, 3H), 1.00-1.30 (m, 5H), 0.75-0.80 (m, 1H), 0.72 (d, 3H, J=6.7), 0.67 (d, 3H, J=6.7).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated to an oily residue
  5. customThe residue was further purified on a BIOTAGE® system (eluted with 75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-41c28805fb9346bc8b00f51291de9e24
Source dataset
uspto-grants-2013_08
Patent number
US08513253B2

Reaction notes

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