(3-{6-[2-(2-Fluoro-4-trifluoromethyl-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-acetonitrile → {6-[3-(2-Amino-ethyl)-phenyl]-2-methoxy-pyrimidin-4-yl}-[2-(2-fluoro-4-trifluoromethyl-phenyl)-ethyl]-amine

HRID 216195Notes

Reaction equation

HRID 216195 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH2:12][CH2:13][NH:14][C:15]1[N:20]=[C:19]([O:21][CH3:22])[N:18]=[C:17]([C:23]2[CH:24]=[C:25]([CH2:29][C:30]#[N:31])[CH:26]=[CH:27][CH:28]=2)[CH:16]=1>CO.Cl>[NH2:31][CH2:30][CH2:29][C:25]1[CH:24]=[C:23]([C:17]2[N:18]=[C:19]([O:21][CH3:22])[N:20]=[C:15]([NH:14][CH2:13][CH2:12][C:3]3[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=3[F:1])[CH:16]=2)[CH:28]=[CH:27][CH:26]=1

Participants

4

Reactant 1

HCID 69071559(3-{6-[2-(2-Fluoro-4-trifluoromethyl-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-acetonitrile

Product 1

HCID 69070707{6-[3-(2-Amino-ethyl)-phenyl]-2-methoxy-pyrimidin-4-yl}-[2-(2-fluoro-4-trifluoromethyl-phenyl)-ethyl]-amineYield 82.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

A solution of (3-{6-[2-(2-fluoro-4-trifluoromethyl-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-acetonitrile (660 mg, 1.53 mmol) in MeOH (20 mL) and concentrated HCl (2 mL) is degassed by bubbling with Argon gas for 5 minutes, and treated with palladium hydroxide on carbon (0.4 g) at room temperature. The mixture is hydrogenated for 15 h at room temperature under hydrogen balloon, filtered through celite, and concentrated in a rotavap. The residue is diluted with water, basified with NaOH solution, and extracted with EtOAc. The extracts are dried (MgSO4), filtered, and concentrated to afford {6-[3-(2-amino-ethyl)-phenyl]-2-methoxy-pyrimidin-4-yl}-[2-(2-fluoro-4-trifluoromethyl-phenyl)-ethyl]-amine (0.55 g). LCMS: RT=1.85 minutes; MS: 435 (M+H).

Workup

  1. customby bubbling with Argon gas for 5 minutes
  2. additiontreated with palladium hydroxide on carbon (0.4 g) at room temperature
  3. filtrationballoon, filtered through celite
  4. concentrationconcentrated in a rotavap
  5. additionThe residue is diluted with water
  6. extractionextracted with EtOAc
  7. dry with materialThe extracts are dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-f346759b6e2042fdb2dd6c7482e638b2
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

Loading…