Sodium Carbonate → tert-butyl 4-[2-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)ethyl]-1,4-diazepane-1-carboxylate

HRID 1818809Notes

Reaction equation

HRID 1818809 reaction equation
Br[CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[S:5]1(=[O:20])=[O:19].[N:21]1([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:27][CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[O:19]=[S:5]1(=[O:20])[N:4]([CH2:3][CH2:2][N:24]2[CH2:25][CH2:26][CH2:27][N:21]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:22][CH2:23]2)[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 687112711-(2-Bromoethyl)-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

Product 1

HCID 68715327tert-butyl 4-[2-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)ethyl]-1,4-diazepane-1-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-(2-bromoethyl)-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (prepared in an analogous manner as described in general procedure VI, 112 mg, 0.317 mmol), tert-butyl 1-homopiperazinecarboxylate (381 mg, 1.90 mmol, 6 equiv.), sodium carbonate (202 mg, 1.90 mmol, 6 equiv.) and ethanol (4 mL) in a sealed reaction vessel was heated at 90° C. for 8 h. After cooling, solvent was removed, and the residue was dissolved in ethyl acetate (15 mL). The resulting solution was washed with an aqueous potassium carbonate solution, water, dried (anhydrous sodium sulfate), and concentrated. The crude liquid was pre-adsorbed onto Florisil and purified via Isco flash column chromatography (4-g redisep silica gel column, 10-60% ethyl acetate/hexane) to give tert-butyl 4-[2-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)ethyl]-1,4-diazepane-1-carboxylate as a viscous, colorless liquid. Yield: 121 mg (81%). MS (ESI) m/z 473.0 ([M+H]+). HPLC purity 100.0% at 210-370 nm, 9.7 min.; Xterra RP18, 3.5 u, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.

Workup

  1. customprepared in an analogous manner
  2. customin a sealed reaction vessel
  3. temperatureAfter cooling
  4. customsolvent was removed
  5. dissolutionthe residue was dissolved in ethyl acetate (15 mL)
  6. washThe resulting solution was washed with an aqueous potassium carbonate solution, water
  7. dry with materialdried (anhydrous sodium sulfate)
  8. concentrationconcentrated
  9. custompurified via Isco flash column chromatography (4-g redisep silica gel column, 10-60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-5fb808d359204448b510c9b1360e884a
Source dataset
uspto-grants-2009_10
Patent number
US07601722B2

Reaction notes

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