Cesium carbonate → tert-butyl (3S,5R)-3-{(2-methylpropyl) {{1-(2-(thiophen-2-yl)ethyl)-1H-benzimidazol-2-yl}carbonyl}amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 1259968

Reaction equation

HRID 1259968 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]([CH2:34][CH:35]([CH3:37])[CH3:36])[C@H:13]1[CH2:18][C@@H:17]([C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:20])[CH2:16][N:15]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:14]1)=[O:11].CS(O[CH2:43][CH2:44][C:45]1[S:46][CH:47]=[CH:48][CH:49]=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:36][CH:35]([CH3:37])[CH2:34][N:12]([C:10]([C:2]1[N:3]([CH2:43][CH2:44][C:45]2[S:46][CH:47]=[CH:48][CH:49]=2)[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=1)=[O:11])[C@H:13]1[CH2:18][C@@H:17]([C:19]([N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)=[O:20])[CH2:16][N:15]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[CH2:14]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 30477232-(2-Thienyl)ethyl methanesulphonate2×HCID 58355717tert-Butyl (3S,5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino)-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Product 1

HCID 58355355tert-butyl (3S,5R)-3-{(2-methylpropyl) {{1-(2-(thiophen-2-yl)ethyl)-1H-benzimidazol-2-yl}carbonyl}amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 85.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

tert-Butyl (3S,5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (150 mg) was dissolved in dimethylformamide (10 ml), 2-(thiophen-2-yl)ethyl methanesulfonate (90 mg) and cesium carbonate (190 mg) were added and the mixture was stirred at 65° C. for 30 min. 2-Thiophen-2-ylethyl methanesulfonate (90 mg) was added, and the mixture was further stirred for 1 hr. The reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (1:9)-ethyl acetate was concentrated under reduced pressure to give the object product (156 mg).

Workup

  1. stirringthe mixture was further stirred for 1 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washa fraction eluted with ethyl acetate-hexane (1:9)-ethyl acetate
  9. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-fe5f72036e934c0faabd3910a7769e62
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Linked notes

Loading…