4-Fluoroaniline → tert-butyl (1S,2R)-2-(4-cyano-3-(4-fluorophenylamino)phenylamino)cyclohexylcarbamate

HRID 84795

Reaction equation

HRID 84795 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].[F:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1.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:30][C:29]1[CH:31]=[CH:32][C:26]([F:25])=[CH:27][CH:28]=1)#[N:9]

Participants

7

Reactant 4

HCID 97314-FluoroanilineHCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 69283621tert-butyl (1S,2R)-2-(3-bromo-4-cyanophenylamino)cyclohexylcarbamate

Product 1

HCID 69283622tert-butyl (1S,2R)-2-(4-cyano-3-(4-fluorophenylamino)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), 4-fluoroaniline (75 uL, 0.792 mmol), BINAP (40 mg, 0.064 mmol), Pd(OAc)2 (25 mg, 0.11 mmol) and K2CO3 (150 mg, 1.08 mmol) in dioxane (3 mL) was degassed with Ar, then was stirred at 100 C for 16 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-(4-fluorophenylamino)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-b3cec6adffb644c09ce4723e70abd249
Source dataset
uspto-grants-2014_09
Patent number
US08846928B2

Linked notes

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