Triethylamine → 3-(3-chlorophenyl)-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 528567

Reaction equation

HRID 528567 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.[CH3:11][O:12][C:13]1[CH:38]=[C:37]([O:39][CH3:40])[CH:36]=[CH:35][C:14]=1[CH2:15][N:16]([C:30]1[S:31][CH:32]=[N:33][N:34]=1)[S:17]([C:20]1[CH:29]=[CH:28][C:23]2[NH:24][C:25](=[O:27])[O:26][C:22]=2[CH:21]=1)(=[O:19])=[O:18].C(N(CC)CC)C.[NH4+].[OH-]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CCOC(C)=O.O.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([N:24]2[C:23]3[CH:28]=[CH:29][C:20]([S:17]([N:16]([CH2:15][C:14]4[CH:35]=[CH:36][C:37]([O:39][CH3:40])=[CH:38][C:13]=4[O:12][CH3:11])[C:30]4[S:31][CH:32]=[N:33][N:34]=4)(=[O:19])=[O:18])=[CH:21][C:22]=3[O:26][C:25]2=[O:27])[CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 2734323(3-Chlorophenyl)boronic acidHCID 89761668N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 897613473-(3-chlorophenyl)-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamideYield 62.4%

Reagents, catalysts & solvents 4

HCID 8895Cupric acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A sealable vial was charged with (3-chlorophenyl)boronic acid (25.6 mg, 0.164 mmol), N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (48.9 mg, 0.109 mmol), 3 Å molecular sieves (powdered, 60 mg), DCM (545 μl), and triethylamine (45.6 μl, 0.327 mmol). Copper (II) acetate (39.6 mg, 0.218 mmol) was added as a solid in a single portion. The mixture was stirred at rt for 48 h. The reaction mixture was poured into a mixture of NH4OH and water (10% NH4OH in H2O), extracted with DCM (2×10 mL), organic layers (which were an emulsion) were combined and washed with water (10 mL) then brine (20 mL), the emulsion resolved upon brine wash. The organic layers were dried (Na2SO4) and concentrated for purification by silica gel MPLC. The residue was taken up in minimal DCM and absorbed onto a 5 g loading cartridge and passed through a silica gel column (12 g) using 98:2 Heptane:EtOAc to 100% EtOAc gradient to afford 3-(3-chlorophenyl)-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (38.0 mg, 0.068 mmol) as a white amorphous solid. m/z (ESI) 559.2 (M+H)+.

Workup

  1. extractionextracted with DCM (2×10 mL), organic layers (which
  2. washwashed with water (10 mL)
  3. washwash
  4. dry with materialThe organic layers were dried (Na2SO4)
  5. concentrationconcentrated for purification by silica gel MPLC
  6. customabsorbed onto a 5 g loading cartridge

Sources & evidence

ORD record
ord-b99a9845c1b74e5aa7069019eabcf636
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Linked notes

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