N-(2,4-dimethoxybenzyl)thiazol-2-amine → N-(2,4-Dimethoxybenzyl)-2-oxo-N-(thiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920278Notes

Reaction equation

HRID 920278 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]=[CH:10][N:11]=1.COC1C=C(OC)C=CC=1CN(C1SN=CN=1)[S:24]([C:27]1[CH:36]=[CH:35][C:30]2[NH:31][C:32](=[O:34])[O:33][C:29]=2[CH:28]=1)(=[O:26])=[O:25]>C1COCC1>[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]=[CH:10][N:11]=1)[S:24]([C:27]1[CH:36]=[CH:35][C:30]2[NH:31][C:32](=[O:34])[O:33][C:29]=2[CH:28]=1)(=[O:26])=[O:25]

Participants

4

Reactant 2

HCID 49931979N-(2,4-dimethoxybenzyl)thiazol-2-amineHCID 89526027N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 89533811N-(2,4-Dimethoxybenzyl)-2-oxo-N-(thiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 41-2 (2.79 g, 11.13 mmol) in THF (71 mL) was cooled to −78° C. Lithium hexamethyldisilizane (LHMDS, 21.4 ml, 21.4 mmol, 1.0M in THF) was added and the reaction was allowed to warm to RT and stir for 30 minutes. Commercially-available, solid 1-5 (4 g, 17.12 mmol) was then added in portions, maintaining the temperature of the reaction mixture at −78° C. The reaction was allowed to slowly warm to RT. After reaching RT, the reaction was quenched with saturated ammonium chloride solution at 0° C. and extracted into EtOAc (3×150 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by normal phase chromatography (0-60% EtOAc in hexane) yielded 41-3 as a solid.

Workup

  1. temperaturemaintaining the temperature of the reaction mixture at −78° C
  2. temperatureto slowly warm to RT
  3. customAfter reaching RT
  4. customthe reaction was quenched with saturated ammonium chloride solution at 0° C.
  5. extractionextracted into EtOAc (3×150 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by normal phase chromatography (0-60% EtOAc in hexane)

Sources & evidence

ORD record
ord-8dbc8b2ea96f40f8bfe79c51f2a013fd
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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