2-Bromo-3-nitrobenzoic acid → HCID 67433398, compound

HRID 2036610Notes

Reaction equation

HRID 2036610 reaction equation
Br[C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH:14]1([NH2:17])[CH2:16][CH2:15]1.C([N:20]([CH:24]([CH3:26])[CH3:25])C(C)C)C>CN(C=O)C.CCOC(C)=O.C1COCC1>[CH:14]1([NH:17][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][CH:9]=[C:10]([N+:11]([O-:13])=[O:12])[C:2]=2[NH:20][CH:24]2[CH2:26][CH2:25]2)[CH2:16][CH2:15]1

Participants

7

Reactant 3

HCID 684522-Bromo-3-nitrobenzoic acidHCID 69828Cyclopropylamine2×HCID 81531Diisopropylethylamine

Product 1

HCID 67433398HCID 67433398, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 2-bromo-3-nitrobenzoic acid (500 mg, 2.03 mmol) in DMF (3 mL) was added cyclopropylamine (0.14 mL, 2.03 mmol), N-ethyl-N-isopropyl-propan-2-amine (0.34 mL, 2.03 mmol) and (1H-benzo[d][1,2,3]triazol-1-yloxy)-tripyrrolidin-1-ylphosphonium hexafluorophosphate(V) (1.27 g, 2.44 mmol). The resulting mixture was stirred at rt for 24 h. The reaction mixture was diluted with EtOAc, washed with water, brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was subjected to flash chromatography on a silica gel column using 0 to 100% gradient of EtOAC:DCM (1:1) in DCM as eluent to give a crude product mixture. To the crude mixture in THF (10 mL) was added cyclopropylamine (0.141 mL, 2.03 mmol) and the resulting mixture was heated under N2 at 60° C. for 18 h. The reaction mixture was diluted with EtOAc, washed with water, brine and dried over magnesium sulfate. After being concentrated in vacuo, the residue was purified by flash chromatography on silica gel using 0 to 100% gradient of EtOAC:DCM (1:1) in DCM as eluent to give N-cyclopropyl-2-(cyclopropylamino)-3-nitrobenzamide: 1H NMR (400 MHz, CDCl3) δ 8.27 (1H, s), 8.01 (1H, d, J=8.0 Hz), 7.45 (1H, d, J=8.0 Hz), 6.62 (1H, t, J=8.0 Hz), 5.98 (1H, s), 2.90-2.65 (2H, m), 0.90-0.78 (2H, m), 0.75-0.65 (2H, m), 0.58-0.50 (2H, m), 0.48-0.40 (2H, m); LC-MS (ESI) m/z 262.1 [M+H]+.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customDCM (1:1) in DCM as eluent to give a crude product mixture
  5. temperaturethe resulting mixture was heated under N2 at 60° C. for 18 h
  6. washwashed with water, brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationAfter being concentrated in vacuo
  9. customthe residue was purified by flash chromatography on silica gel using 0 to 100% gradient of EtOAC

Sources & evidence

ORD record
ord-7d0fcec4e9ea49f48b97e469de96451e
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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