4-Bromobenzylamine → N-(4-Bromobenzyl)-5-((5-methylpyridin-2-yl)methoxy)-2-nitroaniline

HRID 1848711Notes

Reaction equation

HRID 1848711 reaction equation
F[C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[N+:17]([O-:19])=[O:18])[O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][N:8]=1.[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C>C(#N)C>[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH:26][C:2]2[CH:3]=[C:4]([O:5][CH2:6][C:7]3[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][N:8]=3)[CH:14]=[CH:15][C:16]=2[N+:17]([O-:19])=[O:18])=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 775714-BromobenzylamineHCID 81531DiisopropylethylamineHCID 904110842-((3-Fluoro-4-nitrophenoxy)methyl)-5-methylpyridine

Product 1

HCID 90410173N-(4-Bromobenzyl)-5-((5-methylpyridin-2-yl)methoxy)-2-nitroanilineYield 71%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a round-bottomed flask containing 2-((3-fluoro-4-nitrophenoxy)methyl)-5-methylpyridine (68.0 g, 259 mmol) and 4-bromobenzylamine (58 g, 259 mmol) in acetonitrile (680 mL) was added DIPEA (113 mL, 648 mmol). The stirred mixture was then heated to 80° Celsius. After 14.5 h, the mixture was cooled to RT and was concentrated to 261 g. The resulting residue was added to i-PrOH (900 mL) and heated to 70° Celsius until homogeneous. The solution was cooled to RT and the crystalline solids were isolated through filtration. The filter cake was washed with cold i-PrOH (200 mL), the solids were collected and dried in a vacuum oven at 40° Celsius for 3 days to give the title compound (78.4 g, 71%). MS (ESI): mass calcd. for C20H18BrN3O3, 427.1; m/z found, 428.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.66 (t, J=5.9, 1H), 8.36 (d, J=2.1, 1H), 8.16 (d, J=9.5, 1H), 7.57-7.37 (m, 3H), 7.27-7.23 (d incident with solvent signal, 1H), 7.22-7.13 (m, 2H), 6.34 (dd, J=9.5, 2.6, 1H), 6.18 (d, J=2.6, 1H), 5.12 (s, 2H), 4.44 (d, J=5.8, 2H), 2.35 (s, 3H).

Workup

  1. temperaturethe mixture was cooled to RT
  2. concentrationwas concentrated to 261 g
  3. additionThe resulting residue was added to i-PrOH (900 mL)
  4. temperatureheated to 70° Celsius until homogeneous
  5. temperatureThe solution was cooled to RT
  6. customthe crystalline solids were isolated through filtration
  7. washThe filter cake was washed with cold i-PrOH (200 mL)
  8. customthe solids were collected
  9. customdried in a vacuum oven at 40° Celsius for 3 days

Sources & evidence

ORD record
ord-896c89f1104e4244b8ec2c3358460221
Source dataset
uspto-grants-2015_02
Patent number
US08952177B2

Reaction notes

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