Sodium Carbonate → tert-butyl {2-[{2-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}(methyl)amino]ethyl}methylcarbamate

HRID 1818810Notes

Reaction equation

HRID 1818810 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][C:14]=2[F:19])[S:5]1(=[O:21])=[O:20].[CH3:22][N:23]([CH2:31][CH2:32][NH:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[N:6]1[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:4]([CH2:3][CH2:2][N:33]([CH3:34])[CH2:32][CH2:31][N:23]([CH3:22])[C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[S:5]1(=[O:21])=[O:20]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 14403871tert-Butyl methyl(2-(methylamino)ethyl)carbamateHCID 68711997HCID 68711997, compound

Product 1

HCID 86621288tert-butyl {2-[{2-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}(methyl)amino]ethyl}methylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 1-(2-bromoethyl)-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (171 mg, 0.461 mmol), tert-butyl methyl[2-(methylamino)ethyl]carbamate (695 mg, 3.69 mmol, 8 equiv.), sodium carbonate (489 mg, 4.61 mmol, 10 equiv.) and N,N-dimethylformamide (5 mL) was sealed and heated at 125° C. for 5 h. After cooling, the reaction mixture was partitioned between ethyl acetate (40 mL) and water (40 mL). The organic layer was washed with brine, dried (anhydrous sodium sulfate), and concentrated. The crude liquid was pre-adsorbed onto Florisil and purified via Isco flash column chromatography (12-g redisep silica gel column, 15-70% ethyl acetate/hexane) to give tert-butyl {2-[{2-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}(methyl)amino]ethyl}methylcarbamate as a viscous, colorless liquid. Yield: 142 mg (64%). MS (ESI) m/z 479.0 ([M+H]+). HRMS: calcd for C23H31FN4O4S+H+, 479.2123; found (ESI, [M+H]+), 479.2129. HPLC purity 96.6% at 210-370 nm, 9.0 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. customwas sealed
  2. temperatureAfter cooling
  3. customthe reaction mixture was partitioned between ethyl acetate (40 mL) and water (40 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (anhydrous sodium sulfate)
  6. concentrationconcentrated
  7. custompurified via Isco flash column chromatography (12-g redisep silica gel column, 15-70% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-bae0199e3fbc421c993ef6f376dd56a8
Source dataset
uspto-grants-2009_10
Patent number
US07601722B2

Reaction notes

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