4-Methyl-2-nitroaniline → 4-methyl-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline

HRID 1848133Notes

Reaction equation

HRID 1848133 reaction equation
[CH3:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:26][S:27][C:28]1[S:29][C:30]2[CH:36]=[C:35]([CH:37]=O)[CH:34]=[CH:33][C:31]=2[N:32]=1>C(O)(C(F)(F)F)=O>[CH3:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][CH2:37][C:35]2[CH:34]=[CH:33][C:31]3[N:32]=[C:28]([S:27][CH3:26])[S:29][C:30]=3[CH:36]=2)=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1

Participants

5

Reactant 3

HCID 69784-Methyl-2-nitroanilineHCID 5049666Sodium triacetoxyborohydrideHCID 547753816-Benzothiazolecarboxaldehyde, 2-(methylthio)-

Product 1

HCID 866811024-methyl-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroanilineYield 41.4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a stirred mixture of 4-methyl-2-nitroaniline (1 g, 6.5 mmol) in TFA (15 mL) at 0 to 5° C. was added portionwise sodium triacetoxyborohydride (2.78 g, 13.2 mmol) and the mixture was stirred for 10 min. To the reaction mixture was added portionwise 2-(methylthio)benzo[d]thiazole-6-carbaldehyde (1.44 g, 6.9 mmol) from Step 1 of Example 100. After stirring at rt for 4 h, the mixture was poured into ice-water and extracted with EtOAc (100 mL×3). The combined organic layers were washed with saturated aq NaHCO3 (100 mL×2) and brine (100 mL). The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 3% EtOAc in petroleum ether to afford 4-methyl-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline (0.93 g, 41%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.37 (br s, 1H), 8.01 (s, 1H), 7.83 (d, J=8.4 Hz, 1H), 7.71 (s, 1H), 7.38 (dd, J=8.4, 2.4 Hz, 1H), 7.19 (dd, J=8.7, 2.1 Hz, 1H), 8.71 (d, J=8.7 Hz, 1H), 4.83 (d, J=6.0 Hz, 2H), 2.83 (s, 3H), 2.25 (s, 3H); LCMS (ESI) m/z 346 (M+H)+.

Workup

  1. stirringAfter stirring at rt for 4 h
  2. extractionextracted with EtOAc (100 mL×3)
  3. washThe combined organic layers were washed with saturated aq NaHCO3 (100 mL×2) and brine (100 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography
  9. washeluting with 3% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-3fa19bc4dca6452ba29571232e874a6d
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…