Triethylamine → N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}-4-(4-nitrophenyl)piperazine-1-carboxamide

HRID 270015Notes

Reaction equation

HRID 270015 reaction equation
[CH3:1][N:2]([CH3:28])[CH2:3][CH2:4][C@@H:5]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([S:21]([NH2:24])(=[O:23])=[O:22])=[CH:17][C:16]=1[N+:25]([O-:27])=[O:26])[CH2:6][S:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.Cl[C:37](OC1C=CC([N+]([O-])=O)=CC=1)=[O:38].[N+:49]([C:52]1[CH:57]=[CH:56][C:55]([N:58]2[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]2)=[CH:54][CH:53]=1)([O-:51])=[O:50]>ClCCl.CN(C1C=CN=CC=1)C>[CH3:28][N:2]([CH3:1])[CH2:3][CH2:4][C@@H:5]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([S:21]([NH:24][C:37]([N:61]2[CH2:62][CH2:63][N:58]([C:55]3[CH:54]=[CH:53][C:52]([N+:49]([O-:51])=[O:50])=[CH:57][CH:56]=3)[CH2:59][CH2:60]2)=[O:38])(=[O:22])=[O:23])=[CH:17][C:16]=1[N+:25]([O-:27])=[O:26])[CH2:6][S:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 804471-(4-Nitrophenyl)piperazineHCID 821294-Nitrophenyl chloroformateHCID 11502754(R)-4-((4-(Dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrobenzenesulfonamide

Product 1

HCID 10290211N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}-4-(4-nitrophenyl)piperazine-1-carboxamideYield 43%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl} amino)-3-nitrobenzenesulfonamide (prepared according to the procedure described in commonly owned U.S. patent application Ser. No. 09/957,256, filed Sep. 20, 2001, 60 mg, 0.142 mmol) in dichloromethane (2 mL) at room temperature was treated with triethylamine (59 μL, 0.426 mmol) and p-nitrophenyl chloroformate (31 mg, 0.156 mmol), stirred for 2 hours, treated with 1-(4-nitrophenyl)-piperazine (35 mg, 0.169 mmol) and DMAP (17 mg, 0.142 mmol), stirred overnight, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 20% 2N NH3 in methanol/dichloromethane) to provide the desired product (40 mg, 43%). MS (ESI) m/e 658 (M+H)+; 1H NMR (500 MHz, CD3OD) δ 8.5-6.75 (12H, m), 4.16 (1H, m), 3.69 (2H, t), 3.59 (2H, br s), 3.47 (2H, br s), 3.37 (2H, br d), 3.24 (4H, m), 2.87 (6H, s), 2.35-2.15 (2H, m).

Workup

  1. stirringstirred overnight
  2. concentrationconcentrated
  3. customThe concentrate was purified by flash column chromatography on silica gel with 20% 2N NH3 in methanol/dichloromethane)

Sources & evidence

ORD record
ord-eced902509a3497596a74e98845f7e2d
Source dataset
uspto-grants-2008_11
Patent number
US07449485B2

Reaction notes

Loading…