3,5-Dimethylaniline → tert-butyl (1S,2R)-2-(4-cyano-3-(3,5-dimethylphenylamino)phenylamino)cyclohexylcarbamate

HRID 2201027Notes

Reaction equation

HRID 2201027 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[CH3:25][C:26]1[CH:27]=[C:28]([CH:30]=[C:31]([CH3:33])[CH:32]=1)[NH2:29].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:8]([C:7]1[CH:6]=[CH:5][C:4]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:3][C:2]=1[NH:29][C:28]1[CH:30]=[C:31]([CH3:33])[CH:32]=[C:26]([CH3:25])[CH:27]=1)#[N:9]

Participants

7

Reactant 4

HCID 79493,5-DimethylanilineHCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 69283621tert-butyl (1S,2R)-2-(3-bromo-4-cyanophenylamino)cyclohexylcarbamate

Product 1

HCID 69283629tert-butyl (1S,2R)-2-(4-cyano-3-(3,5-dimethylphenylamino)phenylamino)cyclohexylcarbamate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of tert-butyl (1S,2R)-2-(3-bromo-4-cyanophenylamino)cyclohexylcarbamate (150 mg, 0.380 mmol), 3,5-dimethylaniline (95 uL, 0.761 mmol), BINAP (40 mg, 0.064 mmol), Pd(OAc)2 (25 mg, 0.11 mmol) and K2CO3 (150 mg, 1.08 mmol) in dioxane (4 mL) was degassed with Ar, then was stirred at 100 C for 4 h. EtOAc and water were added. The organic phase was separated, washed with 1N HCl, then with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give tert-butyl (1S,2R)-2-(4-cyano-3-(3,5-dimethylphenylamino)phenylamino)cyclohexylcarbamate as a crude residue.

Workup

  1. customwas degassed with Ar
  2. additionEtOAc and water were added
  3. customThe organic phase was separated
  4. washwashed with 1N HCl
  5. dry with materialwith 5% NaHCO3, dried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2209cc8a5a0d4a328d5b8fac350a8fc0
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

Loading…