Diisopropylethylamine → 4-[4-(6-Chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1433087Notes

Reaction equation

HRID 1433087 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]2[CH2:20][CH2:19][NH:18][CH2:17][C:16]2=[O:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[Cl:31][C:32]1[CH:33]=[CH:34][C:35]2[CH:39]=[C:38]([S:40](Cl)(=[O:42])=[O:41])[S:37][C:36]=2[CH:44]=1>C(Cl)Cl.CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]2[CH2:20][CH2:19][N:18]([S:40]([C:38]3[S:37][C:36]4[CH:44]=[C:32]([Cl:31])[CH:33]=[CH:34][C:35]=4[CH:39]=3)(=[O:42])=[O:41])[CH2:17][C:16]2=[O:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 151586416-Chlorobenzo[b]thiophene-2-sulfonyl chlorideHCID 234475144-(2-Oxo-piperazin-1-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 690254374-[4-(6-Chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(2-oxo-piperazin-1-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester (1.44 g, 4.8 mmol) in CH2Cl2 (75 mL) and MeCN (10 mL) is added diisopropylethylamine (1.3 mL, 4.8 mmol) followed by 6-chloro-benzo[b]thiophene-2-sulfonyl chloride (1.29 g, 4.8 mmol), and the reaction is allowed to stir 16 h. The reaction is diluted with CH2Cl2 and washed with 1N HCl and NaHCO3, dried and concentrated. The residue is purified by column chromatography (silica, 40% EtOAc/CH2Cl2) to provide 4-[4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (300 MHz, CDCl3) δ 7.88-7.83 (m, 3H), 7.47 (dd, 1H), 4.1 (br, 2H), 3.86 (s, 2H), 3.46 (bs, 4H), 3.25 (br, 2H), 2.61 (t, 2H), 1.87-1.75 (m, 1H), 1.51 (d, 2H), 1.41 (s, 9H), 1.10 (ddd, 2H); MS (Ion spray) 528 (M+H)+.

Workup

  1. washwashed with 1N HCl and NaHCO3
  2. customdried
  3. concentrationconcentrated
  4. customThe residue is purified by column chromatography (silica, 40% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-8b06f50580be4d87aa60137e6f84df57
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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