Triethylamine → (2R)-2-(N-(4-Chlorobenzenesulfonyl)-N-{1-[2-(4-cyanophenyl)-2-oxo-ethyl]-piperidin-4-ylmethyl}-amino)-4-methyl-pentanoic acid amide

HRID 1893843Notes

Reaction equation

HRID 1893843 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.Cl[CH2:35][C:36]([C:38]1[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=1)=[O:37]>C(Cl)Cl>[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[CH2:14][CH2:15][N:16]([CH2:35][C:36]([C:38]3[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=3)=[O:37])[CH2:17][CH2:18]2)(=[O:9])=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 142493Benzonitrile, 4-(chloroacetyl)-HCID 59001103(2R)-2-[N-(4-Chlorobenzenesulfonyl)-N-(piperidin-4-ylmethyl)amino]-4-methyl-pentanoic acid amide

Product 1

HCID 59001063(2R)-2-(N-(4-Chlorobenzenesulfonyl)-N-{1-[2-(4-cyanophenyl)-2-oxo-ethyl]-piperidin-4-ylmethyl}-amino)-4-methyl-pentanoic acid amideYield 48%

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, 0.050 g, 0.12 mmol) and Et3N (0.040 mL, 0.30 mmol) in CH2Cl2 (2.0 mL) was added 4-(2-chloro-acetyl)-benzonitrile (55 mg, 0.30 mmol). The reaction was stirred at rt for 18 h and then was concentrated to residue. The residue was purified on a BIOTAGE® system (eluted with 80% EtOAc/hexanes) to produce 29 mg (48%) of the desired product as a white solid. MS (ESI), (M+H)+545.16; 1H NMR (CDCl3, 500 MHz) δ 7.72 (d, 2H, J=8.5), 7.50-7.65 (m, 2H), 7.50 (d, 2H, J=7.0), 7.35-7.45 (m, 2H), 6.67 (s, 1H), 5.32 (s, 1H), 4.14 (dd, 1H, J=5.0, 9.0), 3.52 (br s, 1H), 3.28 (t, 1H, J=14), 2.97 (dd, 1H, J=3.5, 14), 2.82 (br s, 1H), 1.00-2.00 (m, 10H), 0.71 (d, 3H, J=6.5), 0.66 (d, 3H, J=6.5).

Workup

  1. concentrationwas concentrated to residue
  2. customThe residue was purified on a BIOTAGE® system (eluted with 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-10c4feaa361c45bb9e2a8fda1814423d
Source dataset
uspto-grants-2013_08
Patent number
US08513253B2

Reaction notes

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