N,N'-Dimethylethylenediamine → HCID 57470975, compound

HRID 1784807Notes

Reaction equation

HRID 1784807 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:5]=[C:6](CC2C=CC(OC)=CC=2)[CH:7]=1.P([O-])([O-])([O-])=[O:25].[K+].[K+].[K+].[N+:32]([C:35]1[CH:43]=[C:42]2[C:38]([CH:39]=[CH:40][NH:41]2)=[CH:37][CH:36]=1)([O-:34])=[O:33].CNCCNC>C(Cl)Cl.[Cu]I.C1(C)C=CC=CC=1>[N+:32]([C:35]1[CH:43]=[C:42]2[C:38]([CH:39]=[CH:40][N:41]2[C:6]2[CH:7]=[C:2]([OH:25])[CH:3]=[C:4]([NH:17][C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[CH:5]=2)=[CH:37][CH:36]=1)([O-:34])=[O:33]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 785026-Nitro-1H-indoleHCID 68841468HCID 68841468, compound

Product 1

HCID 57470975HCID 57470975, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

The resin-bound (3-bromo-5-p-methoxybenzylphenyl)-3-pyridylamine described in Example 22 (200 mg, ca 0.12 mmol) was placed in a 50 mL glass reactor. Copper (I) iodide (0.6 mmol, 114 mg), potassium phosphate (127 mg, 0.6 mmol), toluene (5 mL), 6-nitroindole (0.6 mmol, 98 mg) and N,N′-dimethylethylenediamine (53 mg, 0.6 mmol) were added to the reactor, and the reactor was heated to 110° C. for 16 h under N2 atmosphere. After cooling the reaction mixture to room temperature, the resin was filtered, washed with THF (4×3 mL), MeOH (4×3 mL), H2O (4×3 mL), DMF (3×4 mL), THF (4×3 mL), methylene chloride (4×3 mL) and dried in vacuo. The resin was treated with 2% dimethylsulfide, 50% TFA/methylene chloride (2 mL) for 20 min in a 20 mL glass vial. The slurry of resin in cleavage cocktail was filtered through a fritted syringe to a 20 mL glass vial, washed with methylene chloride (2×1 mL), and the combined solution was evaporated by nitrogen blowing under mild heating to give the crude product which was confirmed by proton NMR and LC/MS analysis. The crude product was passed through a short pad of silica gel using 5% MeOH in methylene chloride. The combined fractions of product were concentrated, and the residue was further purified by prep SFC to obtain 3-(6-nitro-indol-1-yl)-5-(pyridin-3-ylamino)-phenol (4.3 mg, 0.012 mmol). 1H NMR (400 MHz, CD3OD) δ 8.49 (d, J=2.0, 1H), 8.01 (dd, J=8.8, 2.4, 1H), 7.7 (m, 1H), 7.33 (m, 1H), 6.80 (d, J=3.2, 1H), 6.70 (t, J=1.8, 1H), 6.66 (t, J=2.0, 1H), 6.53 (t, J=2.0, 1H).

Workup

  1. customwas placed in a 50 mL glass reactor
  2. temperatureAfter cooling the reaction mixture to room temperature
  3. filtrationthe resin was filtered
  4. washwashed with THF (4×3 mL), MeOH (4×3 mL), H2O (4×3 mL), DMF (3×4 mL), THF (4×3 mL), methylene chloride (4×3 mL)
  5. customdried in vacuo
  6. additionThe resin was treated with 2% dimethylsulfide, 50% TFA/methylene chloride (2 mL) for 20 min in a 20 mL glass vial
  7. filtrationThe slurry of resin in cleavage cocktail was filtered through a fritted syringe to a 20 mL glass vial
  8. washwashed with methylene chloride (2×1 mL)
  9. customthe combined solution was evaporated by nitrogen blowing
  10. temperatureunder mild heating
  11. customto give the crude product which
  12. concentrationThe combined fractions of product were concentrated
  13. customthe residue was further purified by prep SFC

Sources & evidence

ORD record
ord-ded46bef1bef45f9a82d0d90149d9313
Source dataset
uspto-grants-2009_03
Patent number
US07504401B2

Reaction notes

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