Pyridine → HCID 66931693, compound

HRID 1365483Notes

Reaction equation

HRID 1365483 reaction equation
ClC([O:4][C:5]1[CH:10]=CC([N+]([O-])=O)=CC=1)=O.C([N:17]([CH:20]([CH3:22])C)CC)(C)C.[CH:23]1[C:35]2[CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]=2[CH:26]=[CH:25][C:24]=1C=O.[C:38]([O-:41])(=O)[CH3:39].[NH4+:42].[F:43][C:44]1[CH:49]=[CH:48][C:47]([C:50]([C:52]([C:54]2[CH:59]=[CH:58][C:57]([F:60])=[CH:56][CH:55]=2)=O)=O)=[CH:46][CH:45]=1.[N:61]1[CH:66]=CC=CC=1>C(Cl)Cl.CN(C)C=O.C(O)(=O)C>[NH2:17][CH2:20][CH2:22][O:4][CH2:5][CH2:10][O:41][CH2:38][CH2:39][N:42]1[C:50]([C:47]2[CH:48]=[CH:49][C:44]([F:43])=[CH:45][CH:46]=2)=[C:52]([C:54]2[CH:59]=[CH:58][C:57]([F:60])=[CH:56][CH:55]=2)[N:61]=[C:66]1[C:24]1[CH:25]=[CH:26][C:27]2[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:34][C:35]=2[CH:23]=1

Participants

10

Reactant 6

HCID 1049PyridineHCID 34804Fluorene-2-carboxaldehydeHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 1230724,4'-DifluorobenzilHCID 517165Ammonium Acetate

Product 1

HCID 66931693HCID 66931693, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-nitrophenyl chloroformate (0.8 g, 4 mmol) in CH2Cl2 was added to a Wang resin (1 mmol) in CH2Cl2 (9 mL) and pyridine (3 mL). After shaking for 12 h, the resin was washed with 10% dimethylformamide (DMF) in CH2Cl2. A solution of 2,2′-(ethylenedioxy)bisethylenediamine (1.5 g, 10 mmol) and diisopropylethylamine (0.6 g, 5 mmol) in DMF was added to the resin. After shaking for 12 h, the resin was washed with DMF. The resin (7 μmol), 2-fluorenecarboxaldehyde (13 mg, 0.07 mmol), ammonium acetate (22 mg, 0.28 mmol) and 4,4′-difluorobenzil (17 mg, 0.07 mmol) was placed in a reaction vial and suspended in acetic acid (300 μL). The reaction vial was placed in a heat block on a shaker at 100□. The reaction vial was shaken for 5 h. The resin was filtered and washed with DMF, MeOH, and CH2Cl2 several times. The desired compound was cleaved from a solid support by treatment with trifluoroacetic acid (TFA) for 1.5 h. The crude product was directly purified by preparative RP-HPLC with a gradient of 5-100% CH3CN in water (0.1% TFA) over 85 min.

Workup

  1. washthe resin was washed with 10% dimethylformamide (DMF) in CH2Cl2
  2. stirringAfter shaking for 12 h
  3. washthe resin was washed with DMF
  4. customThe reaction
  5. customThe reaction
  6. stirringvial was shaken for 5 h
  7. filtrationThe resin was filtered
  8. washwashed with DMF, MeOH, and CH2Cl2 several times
  9. waitThe desired compound was cleaved from a solid support by treatment with trifluoroacetic acid (TFA) for 1.5 h
  10. customThe crude product was directly purified by preparative RP-HPLC with a gradient of 5-100% CH3CN in water (0.1% TFA) over 85 min.

Sources & evidence

ORD record
ord-e3bbf701b45b4e1ea00635875bb5df29
Source dataset
uspto-grants-2011_02
Patent number
US07888118B2

Reaction notes

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