Sodium Bicarbonate → (+/-)1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one

HRID 618361Notes

Reaction equation

HRID 618361 reaction equation
[CH2:1]([N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[C:4]1=[O:18])[CH3:2].[O:19]=[S:20]1(=[O:36])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[C:22](=[O:29])[N:21]1[CH2:30][CH2:31][CH2:32][C:33](=O)[CH3:34].C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>C(O)(C)C.CCO.[Ti+4].O>[O:19]=[S:20]1(=[O:36])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[C:22](=[O:29])[N:21]1[CH2:30][CH2:31][CH2:32][CH:33]([N:15]1[CH2:16][CH2:17][CH:12]([N:5]2[C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[N:3]([CH2:1][CH3:2])[C:4]2=[O:18])[CH2:13][CH2:14]1)[CH3:34]

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 130591361,1-dioxido-2-(4-oxo-pentyl)-1,2-benzisothiazol-3(2H)-oneHCID 186959461-Ethyl-3-piperidin-4-ylbenzimidazol-2-one

Product 1

HCID 15872112(+/-)1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one

Reagents, catalysts & solvents 4

HCID 114942Titanium cation (4+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidine (319 mg, 1.0 mmol) and 1,1-dioxido-2-(4-oxo-pentyl)-1,2-benzisothiazol-3-(2H)-one (267 mg, 1.0 mmol) in isopropanol (0.4 mL) containing titanium (IV) isoproproxide (0.4 mL, 1.3 mmol) was heated at 55° C. under an argon atmosphere for one hour to give a yellow solution. This solution was cooled to room temperature and diluted with absolute EtOH (4 mL). Sodium cyanoborohydride (70 mg, 1.1 mmol) was added and the reaction mixture stirred for 20 hours. Upon dilution of the reaction with water and addition of aq. NaHCO3, the product was extracted into EtOAc, the extract dried (Na2SO4) and evaporated. The crude residue was chromotographed on a column of silica gel and eluted with a gradient of 0.25-1.25% methanol/chloroform to give (±)1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one (referred to herein as Compound L) as a viscous oil. 1H NMR (400 mHz, CDCl3): d 8.07 (dd, J=5.5 Hz, J=1.4 Hz, 1H), 7.93 (dd, J=6.5 Hz, J=1.1 Hz, 1H), 7.85 (quintet, 2H), 7.35-7.37 (m, 1H), 7.05 (quintet, 2H), 6.98-7.02 (m, 1H), 4.33-4.38 (m, 1H), 3.93 (q, J=7.1 Hz, 2H), 3.85 (dt, J=7.3 Hz, J=3.6 Hz, 2H), 2.86-2.90 (m, 2H), 2.73 (quartet, J=6.8, 1H), 2.57 (broad t, J =10 Hz, 1H), 2.26-2.49 (overlapping quintets, 3H), 1.97 (quintet, 2H), 1.80 (broad d, J=10 Hz, 2H), 1.61-1.69 (m, 1H), 1.41-1.48 (m, 1H), 1.33 (t, J=7.1 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H). The residual oil was converted to its hydrochloride salt and crystallized from isopropanol to give a white crystalline solid, melting point 176° C. (Compound L). Analysis calculated for C26H32N4O4S.HCl0.3 H2O: C, 57.99; H, 6.29; N, 10.41; found: C, 58.03; H, 6.19; N, 10.38.

Workup

  1. customto give a yellow solution
  2. temperatureThis solution was cooled to room temperature
  3. customUpon dilution of the reaction
  4. extractionthe product was extracted into EtOAc
  5. dry with materialthe extract dried (Na2SO4)
  6. customevaporated
  7. washeluted with a gradient of 0.25-1.25% methanol/chloroform

Sources & evidence

ORD record
ord-d645a5f4fb3d48dfa74892ecde432523
Source dataset
uspto-grants-1999_09
Patent number
US05952351

Reaction notes

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