Hydrochloric Acid → 3-(2-Bromopyridin-3-yl)-2H-1,4-benzoxazin-5-amine

HRID 589104Notes

Reaction equation

HRID 589104 reaction equation
Cl.O.[Cl-].[NH4+].[Br:5][C:6]1[C:11]([C:12]2(O)[NH:17][C:16]3[C:18]([N+:22]([O-])=O)=[CH:19][CH:20]=[CH:21][C:15]=3[O:14][CH2:13]2)=[CH:10][CH:9]=[CH:8][N:7]=1>C(O)C.C(#N)C.[Fe]>[Br:5][C:6]1[C:11]([C:12]2[CH2:13][O:14][C:15]3[C:16](=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[N:17]=2)=[CH:10][CH:9]=[CH:8][N:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962Water2×HCID 25517Ammonium ChlorideHCID 904099173-(2-Bromopyridin-3-yl)-5-nitro-3,4-dihydro-2H-1,4-benzoxazin-3-ol

Product 1

HCID 904096563-(2-Bromopyridin-3-yl)-2H-1,4-benzoxazin-5-amineYield 99.2%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of iron (1.71 g, 30.7 mmol) (<10 micron) in ethanol (33.5 mL) was treated with 1.0 M hydrogen chloride in water (3.1 mL, 3.1 mmol) and was stirred at 60° C. for 2 h. The mixture was then cooled to 55-60° C. and treated with 5.0 M ammonium chloride in water (5.3 mL, 26.4 mmol) followed by addition of 3-(2-bromopyridin-3-yl)-5-nitro-3,4-dihydro-2H-1,4-benzoxazin-3-ol (2.16 g, 6.13 mmol, washed with 5 mL ethanol). The resulting suspension was stirred at 60-65° C. for 2 h. The suspension was diluted with acetonitrile to about 100 mL and filtered over Celite. The solid was washed with additional acetonitrile and the filtrate was concentrated to a solid. This solid was dissolved in ethyl acetate which was then dried over magnesium sulfate, filtered, and concentrated to give the desired product (1.85 g, 99%), used without further purification. LCMS calculated for C13H11BrN3O (M+H)+: m/z=304.0, 306.0. found: 304.0, 306.0.

Workup

  1. temperatureThe mixture was then cooled to 55-60° C.
  2. stirringThe resulting suspension was stirred at 60-65° C. for 2 h
  3. filtrationfiltered over Celite
  4. washThe solid was washed with additional acetonitrile
  5. concentrationthe filtrate was concentrated to a solid
  6. dissolutionThis solid was dissolved in ethyl acetate which
  7. dry with materialwas then dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e6550b38f04c48c38656f9f0547a2b15
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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