Ammonium formate → HCID 86617515, compound

HRID 2261973Notes

Reaction equation

HRID 2261973 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2([OH:31])[C:18]3[C:13](=[C:14]([F:20])[CH:15]=[CH:16][C:17]=3[F:19])[C:12](=[O:21])[N:11]2[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]#[CH:29])[C:23]=2[F:30])=[CH:6][C:5]=1[N+:32]([O-])=O)=[N+]=[N-].O1CCCC1.O.C([O-])=O.[NH4+]>C(OCC)(=O)C.[Fe]>[NH2:32][C:5]1[CH:6]=[C:7]([C:10]2([OH:31])[C:18]3[C:13](=[C:14]([F:20])[CH:15]=[CH:16][C:17]=3[F:19])[C:12](=[O:21])[N:11]2[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]#[CH:29])[C:23]=2[F:30])[CH:8]=[CH:9][C:4]=1[NH2:1]

Participants

6

Reactant 3

HCID 2723923Ammonium formateHCID 21881883Oxolane--water (1/1)HCID 86617516HCID 86617516, compound

Product 1

HCID 86617515HCID 86617515, compoundYield 88.6%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(4-azido-3-nitrophenyl)-2-(3-ethynyl-2-fluorophenyl)-4,7-difluoro-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (1.50 mg, 3.20 mmol) in a mixture tetrahydrofurane-water (1:1, 30.0 mL) ammonium formate (2.0 g, 32.0 mmol) was added followed by the addition of iron (1.45 g, 26.0 mmol). The mixture was heated to reflux and stirred for 180 minutes. It was cooled to room temperature and diluted with ethyl acetate. The resulting slurry was filtered through a pad of Celite, and washed with ethyl acetate. It was partitioned with water and the organic layer was washed with water, brine and dried over anhydrous sodium sulfate. Filtration and concentration resulted in an oily product. It was crystallized from diethyl ether by the addition of hexane. The product was collected by filtration, dried in vacuo, to provide 3-(3,4-diaminophenyl)-2-(3-ethynyl-2-fluorophenyl)-4,7-difluoro-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (1.16 g, 88% yield). 1H NMR (400 MHz, CD3OD): 7.57 (s, 1H), 7.42-7.23 (m, 3H), 7.16 (m, 2H), 6.75 (s, 1H), 6.61-6.57 (m, 1H), 3.78 (d, J=8.4 Hz, 1H); MS (EI) for C22H14F3N3O2: 408 (M−).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. filtrationThe resulting slurry was filtered through a pad of Celite
  4. washwashed with ethyl acetate
  5. customIt was partitioned with water
  6. washthe organic layer was washed with water, brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationFiltration and concentration
  9. customresulted in an oily product
  10. customIt was crystallized from diethyl ether by the addition of hexane
  11. filtrationThe product was collected by filtration
  12. customdried in vacuo

Sources & evidence

ORD record
ord-299181a65af747719ed63b0018e1e62d
Source dataset
uspto-grants-2010_12
Patent number
US07846959B2

Reaction notes

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