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 618361ノート

反応式

HRID 618361 の反応式
[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]

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 4

HCID 114942Titanium cation (4+)触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 3776Isopropanol溶媒

反応条件

温度
55 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d645a5f4fb3d48dfa74892ecde432523
出典データセット
uspto-grants-1999_09
特許番号
US05952351

反応ノート

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