O-Phenylenediamine → HCID 25242420, compound

HRID 2367097Notes

Reaction equation

HRID 2367097 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:12]([C:14]3[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=3[C:16](O)=[O:17])=[O:13])[CH:10]=[CH:11][C:5]=2[O:4][CH2:3]1.CN1CCOCC1.C1CN([P+](O[N:47]2N=[N:54][C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][C:48]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1(N)C=CC=CC=1N>CN(C=O)C>[NH2:54][C:49]1[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=1[N:47]1[C:16](=[O:17])[C:15]2[C:14](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]1([C:9]1[CH:10]=[CH:11][C:5]2[O:4][CH2:3][C:2](=[O:1])[NH:7][C:6]=2[CH:8]=1)[OH:13]

Participants

6

Reactant 4

HCID 7243O-PhenylenediamineHCID 79724-MethylmorpholineHCID 17174602-(3-Oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonyl)benzoic acidHCID 2724699PyBOP

Product 1

HCID 25242420HCID 25242420, compoundYield 3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-[(3-Oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]benzoic acid (100 mg, 0.34 mmol.) was taken into DMF (1 mL) followed by addition of 4-methylmorpholine (75 uL, 0.7 mmol.) and PyBOP (177 mg, 0.34 mmol.) and the resulting solution was stirred for 15 minutes at room temperature. o-Phenylenediamine (37 mg, 0.34 mmol.) was added to the solution thus obtained and the mixture was allowed to stir an additional hour then partitioned with ethyl acetate and water. The organic layer was washed with water (3×), 10% aqueous citric acid (2×), saturated aqueous sodium bicarbonate (1×) and brine then dried over anhydrous sodium sulfate. A portion of the residue obtained on filtration and concentration of the organic solution was purified by silica gel flash chromatography (2:1 ethyl acetate:hexanes to 100% ethyl acetate) gave 6-[2-(2-aminophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one (4.0 mg, 3% yield). The remainder of the crude residue was taken into acetic acid (5 mL) and heated to reflux for one hour. The solvent was removed in vacuo and the residue partitioned with ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was dried over anhydrous sodium sulfate and the residue was purified by silica gel flash chromatography (2.5:1 ethyl acetate:hexanes) to give 6-{[2-(1H-benzimidazol-2-yl)phenyl]carbonyl}-2H-1,4-benzoxazin-3(4H)-one (28 mg, 22% yield). 6-[2-(2-Aminophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one: MS (EI) for C22H17N3O4: 388 (MH+). 6-{[2-(1H-Benzimidazol-2-yl)phenyl]carbonyl}-2H-1,4-benzoxazin-3(4H)-one: 1H NMR (400 MHz, d6-DMSO): 12.84 (br s, 1H), 10.75 (br s, 1H), 8.00 (d, 1H), 7.73 (tr, 1H), 7.59 (tr, 1H), 7.44-7.37 (m, 3H), 7.32 (s, 1H), 7.15-7.06 (m, 3H), 6.87 (d, 1H), 4.58 (s, 2H). MS (EI) for C22H15N3O3: 370 (MH+).

Workup

  1. customthus obtained
  2. stirringto stir an additional hour
  3. customthen partitioned with ethyl acetate and water
  4. washThe organic layer was washed with water (3×), 10% aqueous citric acid (2×), saturated aqueous sodium bicarbonate (1×) and brine
  5. dry with materialthen dried over anhydrous sodium sulfate
  6. customA portion of the residue obtained on filtration and concentration of the organic solution
  7. customwas purified by silica gel flash chromatography (2:1 ethyl acetate:hexanes to 100% ethyl acetate)

Sources & evidence

ORD record
ord-42763f897b4346e08fcfe4e68a38d7e9
Source dataset
uspto-grants-2014_04
Patent number
US08697737B2

Reaction notes

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