Ethyl Bromide → 2-(2-(2-(2-((4-(1-Ethylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide

HRID 1473170Notes

Reaction equation

HRID 1473170 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([CH2:20][CH2:21][C:22]4[C:27]([CH2:28][C:29]([NH2:31])=[O:30])=[CH:26][CH:25]=[CH:24][N:23]=4)[C:17]([C:32]([F:35])([F:34])[F:33])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.Br[CH2:37][CH3:38].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:37]([N:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([CH2:20][CH2:21][C:22]4[C:27]([CH2:28][C:29]([NH2:31])=[O:30])=[CH:26][CH:25]=[CH:24][N:23]=4)[C:17]([C:32]([F:35])([F:33])[F:34])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1)[CH3:38]

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 11430Potassium CarbonateHCID 601648082-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide

Product 1

HCID 712091592-(2-(2-(2-((4-(1-Ethylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamideYield 28.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide (32) (74 mg, 0.15 mmol), bromoethane (12 μL, 0.16 mmol) and potassium carbonate (63 mg, 0.46 mmol) in DMF (5 mL) was stirred for 48 h at room temperature under an inert atmosphere. The volatiles were removed under reduced pressure and the residue partitioned between ethyl acetate (20 mL) and saturated sodium hydrogen carbonate solution (20 mL). The aqueous layer was extracted with ethyl acetate (2×30 mL) and the combined organics were washed with brine then dried (MgSO4). The solvent was removed under reduced pressure and the resulting solid was chromatographed (Biotage Isolera: C-18 reverse phase column, 0-100% MeCN in H2O) to give the title compound (38) (22 mg, 28%) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.07 (s, 1H), 8.65 (s, 1H), 8.37 (dd, J=4.8, 1.7 Hz, 1H), 7.65-7.57 (m, 3H), 7.55 (s, 1H), 7.26-7.13 (m, 3H), 7.02 (s, 1H), 3.54 (s, 2H), 3.25 (s, 4H), 2.98 (d, J=11.3 Hz, 2H), 2.48-2.30 (m, 3H), 1.95 (q, J=11.7, 11.3 Hz, 2H), 1.73 (d, J=10.5 Hz, 2H), 1.63 (qd, J=12.4, 3.6 Hz, 2H), 1.03 (t, J=7.2 Hz, 3H). LCMS Method C: rt 4.16 min; m/z 513 [M+H]+.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe residue partitioned between ethyl acetate (20 mL) and saturated sodium hydrogen carbonate solution (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×30 mL)
  4. washthe combined organics were washed with brine
  5. dry with materialthen dried (MgSO4)
  6. customThe solvent was removed under reduced pressure
  7. customthe resulting solid was chromatographed (Biotage Isolera: C-18 reverse phase column, 0-100% MeCN in H2O)

Sources & evidence

ORD record
ord-2a42acfe13bc4c16a109a0d52589d2ac
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

Loading…