Sodium hydride → 4-bromo-5-methoxy-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline

HRID 1848005Notes

Reaction equation

HRID 1848005 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:10]([O:11][CH3:12])=[CH:9][C:7]([NH2:8])=[C:6]([N+:13]([O-:15])=[O:14])[CH:5]=1.Cl[CH2:17][C:18]1[CH:28]=[CH:27][C:21]2[N:22]=[C:23]([S:25][CH3:26])[S:24][C:20]=2[CH:19]=1>CN(C=O)C>[Br:3][C:4]1[C:10]([O:11][CH3:12])=[CH:9][C:7]([NH:8][CH2:17][C:18]2[CH:28]=[CH:27][C:21]3[N:22]=[C:23]([S:25][CH3:26])[S:24][C:20]=3[CH:19]=2)=[C:6]([N+:13]([O-:15])=[O:14])[CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 108004774-Bromo-5-methoxy-2-nitroanilineHCID 866809946-(Chloromethyl)-2-(methylthio)benzo[d]thiazole

Product 1

HCID 866810294-bromo-5-methoxy-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroanilineYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a stirred mixture of DMF (15 mL) and NaH (60% in mineral oil, 75 mg, 1.9 mmol) at −10° C. under argon was added 4-bromo-5-methoxy-2-nitroaniline (490 mg, 2.2 mmol) in one portion. The mixture was stirred for 5 min at −10° C. A solution of 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole from Example 36 (500 mg, 2.2 mmol) in DMF (5 mL) was added dropwise. After stirring at −10° C. for 1 h, the mixture was allowed to warm slowly to rt. The mixture was stirred at rt for 58 h and then partitioned between EtOAc (150 mL) and 1 M aq Na2CO3 (50 mL). The EtOAc layer was separated and washed with water (50 mL) and brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with a gradient of 100% hexanes to 100% EtOAc to afford 4-bromo-5-methoxy-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline (239 mg, 25%) as an orange solid. 1H NMR (300 MHz, DMSO-d6) δ 9.02 (t, J=5.8 Hz, 1H), 8.23 (s, 1H), 8.06 (s, 1H), 7.83 (d, J=8.5 Hz, 1H), 7.53 (d, J=8.3 Hz, 1H), 6.40 (s, 1H), 4.80 (d, J=5.8 Hz, 2H), 3.77 (s, 3H), 2.78 (s, 3H). LCMS (ESI) m/z 440 and 442 (M+H)+.

Workup

  1. stirringAfter stirring at −10° C. for 1 h
  2. temperatureto warm slowly to rt
  3. stirringThe mixture was stirred at rt for 58 h
  4. custompartitioned between EtOAc (150 mL) and 1 M aq Na2CO3 (50 mL)
  5. customThe EtOAc layer was separated
  6. washwashed with water (50 mL) and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by silica gel flash chromatography
  11. washeluting with a gradient of 100% hexanes to 100% EtOAc

Sources & evidence

ORD record
ord-824894cac01f467d9f3d49bb3d179bb6
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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