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

HRID 528566

Reaction equation

HRID 528566 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[N:10][N:11]=1.N#N.C1COCC1.[O:25]=[C:26]1[NH:30][C:29]2[CH:31]=[CH:32][C:33]([S:35](Cl)(=[O:37])=[O:36])=[CH:34][C:28]=2[O:27]1>CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][N:6]([C:7]1[S:8][CH:9]=[N:10][N:11]=1)[S:35]([C:33]1[CH:32]=[CH:31][C:29]2[NH:30][C:26](=[O:25])[O:27][C:28]=2[CH:34]=1)(=[O:37])=[O:36]

Participants

6

Reactant 4

HCID 947NitrogenHCID 8028Tetrahydrofuran2×HCID 1196986-Benzoxazolesulfonyl chloride, 2,3-dihydro-2-oxo-HCID 58042278N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine2×

Product 1

HCID 89761668N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamideYield 71.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-78 °C

Procedure

A round bottom flask was charged with N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (INTERMEDIATE Y) (0.689 g, 2.74 mmol), a septum and N2 line were attached. THF (4.57 mL) was added and when the solution became homogeneous, it was cooled to −78° C. After 10 min, added a THF solution of 2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride (ASDI) (0.621 g, 2.66 mmol) dropwise over 5 minutes (still at −78° C.). When the addition was complete, the cold bath was removed and the mixture was allowed to warm to rt and stirred 18 h. The reaction mixture was poured into sat. aq. NH4Cl, and DCM was added. The layers were separated and the organic layer was extracted with DCM (2×10 mL). The combined organic extracts were dried over Na2SO4 and concentrated under a vacuum. The solution was concentrated for purification by silica gel MPLC. The residue was taken up in minimal DCM and absorbed onto a 25 g loading cartridge and passed through silica gel column (40 g) using 98:2 Heptane:EtOAc to 100% EtOAc gradient to afford N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (0.856 g, 1.909 mmol) as a white amorphous solid. m/z (ESI) 449.0 (M+H)+.

Workup

  1. additionWhen the addition
  2. customthe cold bath was removed
  3. temperatureto warm to rt
  4. additionThe reaction mixture was poured into sat. aq. NH4Cl, and DCM
  5. additionwas added
  6. customThe layers were separated
  7. extractionthe organic layer was extracted with DCM (2×10 mL)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. concentrationconcentrated under a vacuum
  10. concentrationThe solution was concentrated for purification by silica gel MPLC
  11. customabsorbed onto a 25 g loading cartridge

Sources & evidence

ORD record
ord-b1acbc61de9b46b89dce93d762759c9b
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Linked notes

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