Diisopropylethylamine → HCID 118162081, compound

HRID 1749424Notes

Reaction equation

HRID 1749424 reaction equation
Cl.[F:2][C:3]([F:13])([F:12])[C:4]1[CH:9]=[CH:8][N:7]=[CH:6][C:5]=1[CH2:10][NH2:11].CCN(C(C)C)C(C)C.Cl[C:24]1[N:29]=[C:28]([Cl:30])[C:27]([C:31]#[N:32])=[CH:26][N:25]=1>CN(C=O)C>[Cl:30][C:28]1[C:27]([C:31]#[N:32])=[CH:26][N:25]=[C:24]([NH:11][CH2:10][C:5]2[CH:6]=[N:7][CH:8]=[CH:9][C:4]=2[C:3]([F:12])([F:2])[F:13])[N:29]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 140269072,4-Dichloro-5-cyanopyrimidineHCID 17998870C-(4-Trifluoromethyl-pyridin-3-yl)methylamine hydrochloride

Product 1

HCID 118162081HCID 118162081, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (4-(trifluoromethyl)pyridin-3-yl)methanamine hydrochloride (1.0 equiv.) in DMF (1.0 M) was added DIEA (2.5 equiv.). The reaction was cooled to −20° C. (ice/brine bath) then added 2,4-dichloropyrimidine-5-carbonitrile (1.0 equiv.). The reaction mixture was stirred for 10 min, then removed from the ice bath and allowed to stir for 30 min. The reaction mixture was diluted with ethyl acetate and partitioned with water. The organic layer was separated and volatile solvents were removed under reduced pressure. The residue was purified using silica gel chromatography (5-50% ethyl acetate in hexanes). The desired fractions were combined and volatile solvents were removed under reduced pressure. The residue was triturated in 10% ethyl acetate in hexanes, filtered, washed with hexanes, and dried in vacuo to afford 4-chloro-2-(((4-(trifluoromethyl)pyridin-3-yl)methyl)amino)pyrimidine-5-carbonitrile (43.0% yield) as a pale tan solid; MS (ESI) m/z 314.0 [M+1]+

Workup

  1. customremoved from the ice bath
  2. stirringto stir for 30 min
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. custompartitioned with water
  5. customThe organic layer was separated
  6. customvolatile solvents were removed under reduced pressure
  7. customThe residue was purified
  8. customvolatile solvents were removed under reduced pressure
  9. customThe residue was triturated in 10% ethyl acetate in hexanes
  10. filtrationfiltered
  11. washwashed with hexanes
  12. customdried in vacuo

Sources & evidence

ORD record
ord-7470b0121d304108be3a062b61a5bc22
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

Loading…