4-Methoxybenzenesulfonyl chloride → Ethyl[{4-[(dodecylamino)carbonyl]benzyl}({1-[(4-methoxyphenyl)-sulfonyl]piperidin-4-yl}methyl)amino](oxo)acetate

HRID 735838Notes

Reaction equation

HRID 735838 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:38])[C:6]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([NH:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[O:24])=[CH:19][CH:18]=1)[CH2:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)=[O:7])[CH3:3].COC1C(CCN)=CC(OC)=C([125I])C=1.[CH3:53][O:54][C:55]1[CH:60]=[CH:59][C:58]([S:61](Cl)(=[O:63])=[O:62])=[CH:57][CH:56]=1>CN(C1C=CN=CC=1)C.C1COCC1>[CH2:2]([O:4][C:5](=[O:38])[C:6]([N:8]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]([NH:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[O:24])=[CH:21][CH:22]=1)[CH2:9][CH:10]1[CH2:11][CH2:12][N:13]([S:61]([C:58]2[CH:57]=[CH:56][C:55]([O:54][CH3:53])=[CH:60][CH:59]=2)(=[O:63])=[O:62])[CH2:14][CH2:15]1)=[O:7])[CH3:3]

Participants

6

Reactant 3

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 195464Benzeneethanamine, 4-(iodo-125I)-2,5-dimethoxy-HCID 67188110Ethyl[{4-[(dodecylamino)carbonyl]benzyl}(piperidin-4-ylmethyl)amino](oxo)acetate hydrochloride

Product 1

HCID 67186066Ethyl[{4-[(dodecylamino)carbonyl]benzyl}({1-[(4-methoxyphenyl)-sulfonyl]piperidin-4-yl}methyl)amino](oxo)acetateYield 89%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl[{4-[(dodecylamino)carbonyl]benzyl}(piperidin-4-ylmethyl)amino](oxo)acetate hydrochloride (900 mg, 1.63 mmol), DIAE (527 mg, 4.07 mmol) and DMAP (20 mg, 0.16 mmol) in anhydrous THF (50 mL) was added 4-methoxybenzene-sulfonyl chloride (404 mg, 1.96 mmol) dissolved in THF (2.0 mL). The reaction mixture was stirred 14 h at rt. The solvent was evaporated and the resulting residue was dissolved in DCM (100 mL), washed with water (20 mL) and the aqueous layer was extracted with DCM (3×50 mL). The combined organic layers were dried over MgSO4, filtered and evaporated under vacuum. The crude product was purified by column chromatography over silica gel (AcOEt/c-Hex 1/4 to 1/1 in about 1 h) to give the title compound as a white foam (992 mg, 89%). 1H NMR (CDCl3, 300 MHz) δ 7.76 (d, 2H, J=8.3 Hz), 7.69 (d, 2H, J=9.2 Hz), 7.27 (t, 2H, J=7.9 Hz), 7.07 (m, 2H), 6.12 (m, 1H), 4.60 (s, 1H), 4.48 (s, 1H), 3.89 (s, 3H), 3.76 (m, 2H), 3.13 (d, 1H, J=6.8 Hz), 3.07 (d, 1H, J=7.0 Hz), 2.32-2.12 (m, 2H), 1.80-1.55 (m, 6H), 1.45-1.20 (m, 24H), 0.89 (t, 3H, J=7.9 Hz). M−(APCI): 684.4. HPLC (Condition A), Rt: 6.84 min (HPLC purity: 99.7%).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe resulting residue was dissolved in DCM (100 mL)
  3. washwashed with water (20 mL)
  4. extractionthe aqueous layer was extracted with DCM (3×50 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated under vacuum
  8. customThe crude product was purified by column chromatography over silica gel (AcOEt/c-Hex 1/4 to 1/1 in about 1 h)

Sources & evidence

ORD record
ord-64afedfdedee4c20a15f91026f8b15dc
Source dataset
uspto-grants-2009_09
Patent number
US07592477B2

Reaction notes

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