Dimethylformamide → HCID 54675650, compound

HRID 2203325Notes

Reaction equation

HRID 2203325 reaction equation
CN(C=O)C.[NH2:6][C:7]1[C:8]2[C:32]([CH3:39])([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:31](=[O:40])[NH:30][C:9]=2[N:10]=[C:11]([NH:13]/[N:14]=[C:15](/[C:22]2[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=2Br)\[CH2:16][CH2:17][C:18]([F:21])([F:20])[F:19])[N:12]=1.CNCCNC>CCOC(C)=O.[Cu]I>[NH2:6][C:7]1[C:8]2[C:32]([CH3:39])([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:31](=[O:40])[NH:30][C:9]=2[N:10]=[C:11]([N:13]2[C:23]3[C:22](=[CH:27][C:26]([Cl:28])=[CH:25][CH:24]=3)[C:15]([CH2:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[N:14]2)[N:12]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 8070N,N'-DimethylethylenediamineHCID 89438496HCID 89438496, compound

Product 1

HCID 54675650HCID 54675650, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

A DMF (3 mL) solution of the crude intermediate from Step C (77 mg, 0.135 mmol), copper (I) iodide (25.7 mg, 0.135 mmol), and N,N′-dimethylethylenediamine (14.3 mg, 0.162 mmol) was stirred at ambient temperature for 1 hour. The reaction mixture was diluted with EtOAc and washed with 10% aqueous NH4OH solution (2×), water (3×), and brine. The organic phase was JO dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by reverse phase HPLC using a water/acetonitrile (with 0.1% TFA) gradient. The isolated material was converted to the free base by suspending in EtOAc, washing with aqueous saturated NaHCO3 solution (2×) and brine. The solution was dried over anhydrous MgSO4, filtered, concentrated. The residue was purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated compound as a racemic mixture. The enantiomers were separated on a ChiralPak IB column using 7% EtOH/heptane as eluent to give the indicated compound. Data is given for the faster eluting enantiomer. 1H NMR (500 MHz, DMSO-d6): δ (ppm) 11.23 (1H, s), 8.86 (1H, d, J=9.1 Hz), 8.07 (1H, d, J=2.1 Hz), 7.52 (1H, dd, J=9.0, 2.1 Hz), 7.37-7.25 (5H, m), 6.75 (2H, s), 3.30-3.20 (2H, m), 2.88-2.76 (2H, m), 1.79 (3H, s). m/z=487.1 (M+H).

Workup

  1. washwashed with 10% aqueous NH4OH solution (2×), water (3×), and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC
  6. washwashing with aqueous saturated NaHCO3 solution (2×) and brine
  7. dry with materialThe solution was dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography
  11. customto give the indicated compound as a racemic mixture
  12. customThe enantiomers were separated on a ChiralPak IB column
  13. customto give the indicated compound
  14. washfaster eluting enantiomer

Sources & evidence

ORD record
ord-ecc7fdfbc2964dc098d15717858151cf
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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