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

HRID 270014Notes

Reaction equation

HRID 270014 reaction equation
[C:1]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.ClC(Cl)(O[C:24](=[O:30])OC(Cl)(Cl)Cl)Cl.[CH3:32][N:33]([CH3:59])[CH2:34][CH2:35][C@@H:36]([NH:45][C:46]1[CH:51]=[CH:50][C:49]([S:52]([NH2:55])(=[O:54])=[O:53])=[CH:48][C:47]=1[N+:56]([O-:58])=[O:57])[CH2:37][S:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>ClCCl.CN(C1C=CN=CC=1)C>[CH3:59][N:33]([CH3:32])[CH2:34][CH2:35][C@@H:36]([NH:45][C:46]1[CH:51]=[CH:50][C:49]([S:52]([NH:55][C:24]([N:10]2[CH2:11][CH2:12][N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8][CH2:9]2)=[O:30])(=[O:53])=[O:54])=[CH:48][C:47]=1[N+:56]([O-:58])=[O:57])[CH2:37][S:38][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

7

Reactant 4

HCID 70961-PhenylpiperazineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 11502754(R)-4-((4-(Dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrobenzenesulfonamide

Product 1

HCID 10196923N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}-4-phenylpiperazine-1-carboxamideYield 41%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-phenylpiperazine (30 mg, 0.185 mmol) in dichloromethane (2 mL) was treated with triethylamine (77 μL, 0.555 mmol), cooled to 0° C., treated with triphosgene (33 mg, 0.111 mmol), warmed to room temperature, stirred for 1 hour, treated with 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, 86 mg, 0.204 mmol) and DMAP (23 mg, 0.185 mmol), stirred overnight, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 20% 2N NH3 in methanol/dichloromethaneto provide the desired product (46 mg, 41%). MS (ESI) m/e 613 (M+H)+; 1H NMR (500 MHz, CD3OD) δ 8.0-6.75 (13H, m), 4.15 (1H, m), 3.59 (2H, t), 3.39 (4H, m), 3.25 (4H, m), 3.16 (2H, t), 2.88 (6H, s), 2.35-2.15 (2H, m).

Workup

  1. temperaturewarmed to room temperature
  2. customprepared
  3. concentrationconcentrated
  4. customThe concentrate was purified by flash column chromatography on silica gel with 20% 2N NH3 in methanol/

Sources & evidence

ORD record
ord-46ea0d00aa1444cb8182b49aa376c00a
Source dataset
uspto-grants-2008_11
Patent number
US07449485B2

Reaction notes

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