Diisopropylethylamine → HCID 86657191, compound

HRID 1429240Notes

Reaction equation

HRID 1429240 reaction equation
CS(O[C@H:6]([C:26]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[C:29]([Cl:35])=[CH:28][C:27]=1[F:36])[CH2:7][CH2:8][C@H:9](OS(C)(=O)=O)[C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([Cl:19])=[CH:12][C:11]=1[F:20])(=O)=O.[F:37][C:38]1[CH:39]=[C:40]([CH:42]=[C:43]([F:51])[C:44]=1[N:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1)[NH2:41].CCN(C(C)C)C(C)C>CC#N>[Cl:19][C:13]1[C:14]([N+:16]([O-:18])=[O:17])=[CH:15][C:10]([C@H:9]2[CH2:8][CH2:7][C@H:6]([C:26]3[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[C:29]([Cl:35])=[CH:28][C:27]=3[F:36])[N:41]2[C:40]2[CH:39]=[C:38]([F:37])[C:44]([N:45]3[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50]3)=[C:43]([F:51])[CH:42]=2)=[C:11]([F:20])[CH:12]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 580320571,4-Butanediol, 1,4-bis(4-chloro-2-fluoro-5-nitrophenyl)-, 1,4-dimethanesulfonate, (1S,4S)-HCID 610166693,5-difluoro-4-(piperidin-1-yl)aniline

Product 1

HCID 86657191HCID 86657191, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (1S,4S)-1,4-bis(4-chloro-2-fluoro-5-nitrophenyl)butane-1,4-diyl dimethanesulfonate (500 mg, 0.843 mmol) in CH3CN (4.5 ml) was added 3,5-difluoro-4-(piperidin-1-yl)aniline (358 mg, 1.685 mmol) and Hunig's base (0.736 mL, 4.21 mmol). The suspension was heated at 75° C. for 24 hours. Solvent was removed by rotary evaporation and the residue was dissolved in EtOAc, washed with 1 N HCl, H2O, brine, dried (MgSO4), filtered and concentrated. The crude product was chromatographed on an ISCO 24 g silica gel cartridge eluting with 20-70% CH2Cl2/hexane to provide the title compound with some of the corresponding cis-pyrrolidine isomer.

Workup

  1. customSolvent was removed by rotary evaporation
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with 1 N HCl, H2O, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was chromatographed on an ISCO 24 g silica gel cartridge
  8. washeluting with 20-70% CH2Cl2/hexane

Sources & evidence

ORD record
ord-bfd9c2aac9654517b45b8432782dea37
Source dataset
uspto-grants-2015_01
Patent number
US08937150B2

Reaction notes

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