Acetic Acid → 4-bromo-5-methoxy-N1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)benzene-1,2-diamine

HRID 1848006Notes

Reaction equation

HRID 1848006 reaction equation
[Br:1][C:2]1[C:20]([O:21][CH3:22])=[CH:19][C:5]([NH:6][CH2:7][C:8]2[CH:18]=[CH:17][C:11]3[N:12]=[C:13]([S:15][CH3:16])[S:14][C:10]=3[CH:9]=2)=[C:4]([N+:23]([O-])=O)[CH:3]=1.CC(O)=O.CO>CCO.[Zn]>[Br:1][C:2]1[CH:3]=[C:4]([NH2:23])[C:5]([NH:6][CH2:7][C:8]2[CH:18]=[CH:17][C:11]3[N:12]=[C:13]([S:15][CH3:16])[S:14][C:10]=3[CH:9]=2)=[CH:19][C:20]=1[O:21][CH3:22]

Participants

6

Reactant 3

HCID 176Acetic Acid2×HCID 887MethanolHCID 866810294-bromo-5-methoxy-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline

Product 1

HCID 866810304-bromo-5-methoxy-N1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)benzene-1,2-diamineYield 61%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 702EthanolSolvent

Procedure

To a stirred suspension of 4-bromo-5-methoxy-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline (212 mg, 0.5 mmol) from Step 1 of this Example in EtOH (4 mL) and HOAc (2 mL) at 0° C. under argon was added zinc powder (160 mg, 2.4 mmol) in one portion. After 1.5 h at 0° C., MeOH (5 mL), additional HOAc (2 mL), and zinc powder (160 mg, 2.4 mmol) were added. The mixture was allowed to warm to rt and stirred for 18 h. The mixture was filtered and the filtrate was cooled to 0° C. The pH of the filtrate was adjusted to pH˜9 by addition of solid Na2CO3. The mixture was then partitioned between EtOAc (150 mL) and water (100 mL). The EtOAc layer was separated, dried over Na2SO4, filtered, and 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-N1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)benzene-1,2-diamine (120 mg, 61%). LCMS (ESI) m/z 410 and 412 (M+H)+.

Workup

  1. filtrationThe mixture was filtered
  2. temperaturethe filtrate was cooled to 0° C
  3. additionThe pH of the filtrate was adjusted to pH˜9 by addition of solid Na2CO3
  4. customThe mixture was then partitioned between EtOAc (150 mL) and water (100 mL)
  5. customThe EtOAc layer was separated
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography
  10. washeluting with a gradient of 100% hexanes to 100% EtOAc

Sources & evidence

ORD record
ord-af76f00d2b0148798318202ae2f80d2f
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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