Dimethylformamide → HCID 21904921, compound

HRID 1247422Notes

Reaction equation

HRID 1247422 reaction equation
[NH2:1][C:2]1[C:3]([F:24])=[C:4]([CH:9]([O:22][CH3:23])[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)=[O:11])[C:5]([F:8])=[CH:6][CH:7]=1.C(N(C(C)C)[CH:28]([CH3:30])[CH3:29])C.IC(C)C.CN(C=O)C>C1COCC1.O>[C:20]([C:17]1[CH:18]=[CH:19][C:14]([CH2:13][NH:12][C:10](=[O:11])[CH:9]([C:4]2[C:5]([F:8])=[CH:6][CH:7]=[C:2]([NH:1][CH:28]([CH3:30])[CH3:29])[C:3]=2[F:24])[O:22][CH3:23])=[CH:15][CH:16]=1)#[N:21]

Participants

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 6362Isopropyl iodide3×HCID 81531Diisopropylethylamine3×HCID 21905257HCID 21905257, compound

Product 1

HCID 21904921HCID 21904921, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (RS)-2-(3-amino-2,6-difluoro-phenyl)-N-(4-cyano-benzyl)-2-methoxy-acetamide (example 307.5) 81 mg) at rt in THF (5 ml) under an argon atmosphere were added N-ethyldiisopropylamine (0.017 ml) and 2-iodopropane (0.01 ml). The mixture was heated to reflux and stirring was continued for 17 h. More 2-iodopropane (0.1 ml) and N-ethyldiisopropylamine (0.17 ml) were added and stirring at reflux was continued for 7 h. DMF (5 ml) was added and the mixture was stirred at 120° C. for 21 h. The mixture had turned to light brown. More DMF (5 ml), N-ethyldiisopropylamine (0.35 ml,) and 2-iodopropane (0.2 ml) were added and stirring at 90° C. was continued for 17 h. The mixture was cooled to rt, diluted with 20 ml water and extracted with EtOAc. The combined organics were washed with water and brine, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (cyclohexane=>cyclohexane/EtOAc 1:1) to give N-(4-cyano-benzyl)-2-(2,6-difluoro-3-isopropylamino-phenyl)-2-methoxy-acetamide (28 mg) as light brown gum.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. stirringstirring
  4. temperatureat reflux
  5. waitwas continued for 7 h
  6. stirringthe mixture was stirred at 120° C. for 21 h
  7. stirringstirring at 90° C.
  8. waitwas continued for 17 h
  9. extractionextracted with EtOAc
  10. washThe combined organics were washed with water and brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude product was purified by column chromatography (cyclohexane=>cyclohexane/EtOAc 1:1)

Sources & evidence

ORD record
ord-9e8b325a6072416cb8e787ceb2429e25
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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