HCID 68485937, compound → 5-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-1,3-benzenedicarbonitrile

HRID 1874901Notes

Reaction equation

HRID 1874901 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17](Br)[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[C:21]([Zn]C#N)#[N:22]>CN(C=O)C.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([C:14]#[N:15])[CH:16]=[C:17]([C:21]#[N:22])[CH:18]=2)[C:6]([Cl:9])=[CH:7][CH:8]=1

Participants

6

Reactant 2

HCID 68485937HCID 68485937, compoundHCID 178514179HCID 178514179, compound

Product 1

HCID 684872335-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-1,3-benzenedicarbonitrileYield 77.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.355 g, 0.998 mmol) was combined with dicyanozinc (0.100 g, 0.852 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.100 mmol) in DMF (3 mL) and heated at 120° C. for 25 min in a microwave reactor under an inert atmosphere. The reaction mixture was diluted with EtOAc, washed twice with saturated aqueous NaHCO3 and twice with water, dried over MgSO4, filtered and concentrated to dryness. The residue was dissolved in CH3OH and gravity filtered through a StratoSpheres™ PL-Thiol MP SPE+ cartridge. The filtrate was concentrated to dryness and purified on 40 g silica gel eluted successively with EtOAc and 10% CH3OH/DCM to give 5-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-1,3-benzenedicarbonitrile (0.200 g, 0.663 mmol, 66.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.22 (s, 1H), 7.91 (s, 2H), 7.46-7.57 (m, 2H), 3.77 (s, 2H), 1.90 (br. s., 2H). LC-MS (ES+) m/z 302.27, 304.19 [M+H].

Workup

  1. washwashed twice with saturated aqueous NaHCO3 and twice with water
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. dissolutionThe residue was dissolved in CH3OH
  6. filtrationgravity filtered through a StratoSpheres™ PL-Thiol MP SPE+ cartridge
  7. concentrationThe filtrate was concentrated to dryness
  8. custompurified on 40 g silica gel
  9. washeluted successively with EtOAc and 10% CH3OH/DCM

Sources & evidence

ORD record
ord-5ade8d49ee67472983ef7af1e1f95f45
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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