Water → 1,1-dioxido-2-(4-(4-(3-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one

HRID 618359Notes

Reaction equation

HRID 618359 reaction equation
[CH2:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[C:5]1=[O:19])[CH2:2][CH3:3].[O:20]=[S:21]1(=[O:37])[C:25]2[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:24]=2[C:23](=[O:31])[N:22]1[CH2:32][CH2:33][CH2:34][CH2:35]Br.C(N(CC)CC)C.O>CN(C)C=O>[O:37]=[S:21]1(=[O:20])[C:25]2[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:24]=2[C:23](=[O:31])[N:22]1[CH2:32][CH2:33][CH2:34][CH2:35][N:16]1[CH2:17][CH2:18][CH:13]([N:6]2[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:4]([CH2:1][CH2:2][CH3:3])[C:5]2=[O:19])[CH2:14][CH2:15]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 133659801,2-Benzisothiazol-3(2H)-one, 2-(4-bromobutyl)-5-chloro-, 1,1-dioxideHCID 158951351-(Piperidin-4-yl)-3-propyl-1,3-dihydro-2H-benzimidazol-2-one

Product 1

HCID 158721111,1-dioxido-2-(4-(4-(3-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4-(3-propyl-2-oxo-1-benzimidazolinyl)piperidine (440 mg, 1.7 mmol) in dry dimethylformamide (6 mL), under an argon atmosphere was added 1,1-dioxido-2-(4-bromobutyl)-5-chloro-1,2-benzisothiazol-3(2H)-one (615 mg, 1.74 mmol, prepared as shown in Example 22) followed by triethylamine (0.25 mL, 1.8 mmol). This solution was heated at 50° C. for four hours and then cooled to room temperature as water was added. The product was extracted, dried (Na2SO4) and evaporated. The residue was chromatographed on a column of silica gel eluting with a gradient of 0.5-2% methanol/chloroform containing 0.2% NH4OH to give 1,1-dioxido-2-(4-(4-(3-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one as a viscous oil. 1H NMR (400 MHz, CDCl3): d 8.02 (s, 1H), 7.84 (quartet, J=8 Hz, 2H), 7.30 (broad d, 1H), 7.05 (broad quintet, 2H), 6.98 (broad d, J=8 Hz, 1H), 4.40 (multiplet, 1H), 3.84 (t, J=7.1 Hz, 4H), 3.07 (broad d, J=11.1 Hz, 2H),2.43-2.47 (m, 4H),2.14 (broad t, J=11 Hz, 2H), 1.88-1.93 (quintet, 2H), 1.75-1.81 (multiplet, 4H), 1.62-1.66 (multiplet, 2H), 0.97 (t, J=7.3 Hz, 3H). This oil was converted to its hydrochloride salt and crystallized from methanol upon addition of diethyl ether to give a crystalline white solid, melting point 225-227° C.: Analysis calculated for C26H31ClN4O4S.HCl: C, 55.02; H, 5.68; N, 9.87; found: C, 54.76; H, 5.66; N, 9.80.

Workup

  1. additionwas added
  2. extractionThe product was extracted
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customThe residue was chromatographed on a column of silica gel eluting with a gradient of 0.5-2% methanol/chloroform containing 0.2% NH4OH

Sources & evidence

ORD record
ord-8f3927cccfac4228bfb245abef720770
Source dataset
uspto-grants-1999_09
Patent number
US05952351

Reaction notes

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