N-(4-methoxybenzyl)-3-oxo-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide → N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528520Notes

Reaction equation

HRID 528520 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]([C:23]2[S:27][N:26]=[CH:25][N:24]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][C:19](=O)[CH2:18][O:17][C:16]=3[CH:22]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([C:23]2[S:27][N:26]=[CH:25][N:24]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:22]=2)(=[O:11])=[O:10])=[CH:28][CH:29]=1

Participants

3

Reactant 1

HCID 89761418N-(4-methoxybenzyl)-3-oxo-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2×

Product 1

HCID 89761532N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of borane tetrahydrofuran complex, 1.0 M in tetrahydrofuran (4.76 mL, 4.76 mmol) was added dropwise to a mixture of N-(4-methoxybenzyl)-3-oxo-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE K, 1.372 g, 3.17 mmol) in THF (15.86 mL) to form a heterogeneous mixture at 0° C. Gas evolution was observed upon addition, as well as gradual solubilization. After the addition, the reaction was warmed to RT for 5 h. The reaction was then quenched with MeOH (16.0 mL) and stirred overnight at room temperature. The reaction was then concentrated under a vacuum, and re-diluted with MeOH, and concentrated (×2). The resulting material was diluted once more in methanol and the solids were triturated and filtered, washing with methanol to yield 1.122 g of INTERMEDIATE L, N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (1.122 g, 2.68 mmol, 85%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.34-3.38 (m, 2 H) 3.72 (s, 3 H) 4.10 (t, J=4.40 Hz, 2 H) 5.03 (s, 2 H) 6.62-6.66 (m, 1 H) 6.82-6.89 (m, 2 H) 7.04 (d, J=2.35 Hz, 1 H) 7.16-7.21 (m, 1 H) 7.25-7.31 (m, 2 H) 8.35 (s, 1 H). m/z (ESI) 418.8 (M+H)+.

Workup

  1. customto form a heterogeneous mixture at 0° C
  2. additionGas evolution was observed upon addition
  3. additionAfter the addition
  4. customThe reaction was then quenched with MeOH (16.0 mL)
  5. concentrationThe reaction was then concentrated under a vacuum
  6. additionre-diluted with MeOH
  7. concentrationconcentrated (×2)
  8. additionThe resulting material was diluted once more in methanol
  9. customthe solids were triturated
  10. filtrationfiltered
  11. washwashing with methanol

Sources & evidence

ORD record
ord-7eaa3c72a5834d88ae29cd1cb4e6728f
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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