Dimethyl Sulfoxide → 4-(4-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one

HRID 1685218Notes

Reaction equation

HRID 1685218 reaction equation
Cl.Cl.Cl.[F:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[N:14]([CH2:16][CH2:17][N:18]([CH3:20])[CH3:19])[CH:15]=2)=[CH:7][C:6]=1[C:27]([F:30])([F:29])[F:28].CS(C)=O.Cl[C:36]1[C:37]2[CH2:44][C:43](=[O:45])[N:42]([CH2:46][C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][C:48]=3[O:55][CH3:56])[C:38]=2[N:39]=[CH:40][N:41]=1>O>[CH3:19][N:18]([CH3:20])[CH2:17][CH2:16][N:14]1[CH:15]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([F:4])=[C:6]([C:27]([F:28])([F:29])[F:30])[CH:7]=2)[N:12]=[C:13]1[CH:21]1[CH2:26][CH2:25][N:24]([C:36]2[C:37]3[CH2:44][C:43](=[O:45])[N:42]([CH2:46][C:47]4[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][C:48]=4[O:55][CH3:56])[C:38]=3[N:39]=[CH:40][N:41]=2)[CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 679Dimethyl Sulfoxide2×HCID 569717344-chloro-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-oneHCID 866416212-(4-(4-Fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine trihydrochloride

Product 1

HCID 672649744-(4-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-oneYield 79.75%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
62.5 °C

Procedure

Combine 2-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine trihydrochloride (98.76 g, 1 eq), DMSO (395 mL) and 4-chloro-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (1.1 eq). Heat the resulting suspension to 60-65° C. then add TEA (6 eq). Stir for 6 hours. Add DMSO (395 mL) and water (150 mL) as a stream and stir the resulting suspension for 1 hour at 45-38° C. Filter the slurry and wash the solids with a mixture of DMSO (1 vol) and water (1 vol) two times. Further wash the solids with water (3×200 mL), methanol (3×200 mL) and heptane (3×200 mL). Dry the cake on the filter to afford the target compound (106.5 g, 79.75% yield) as a tan solid. 1H NMR (400 MHz, DMSO): 8.18 (s, 1H), 7.99-7.95 (m, 2H), 7.71 (s, 1H), 7.43-7.39 (m, 2H), 6.76 (d, J=7.1 Hz, 1H), 6.54 (d, J=2 Hz 1H), 6.38-6.35 (m, 1H), 4.67 (s, 2H), 4.49 (d, J=13.1 Hz, 2H), 4.03 (t, J=6.52, 2H), 3.89 (s, 2H), 3.78 (s, 3H), 3.69 (s, 3H), 3.15-3.09 (m, 3H), 2.57 (t, J=6.6 Hz, 2H), 2.18 (s, 6H), 1.89-1.74 (m, 4H).

Workup

  1. filtrationFilter the slurry
  2. washwash the solids
  3. additionwith a mixture of DMSO (1 vol) and water (1 vol) two times
  4. washFurther wash the solids with water (3×200 mL), methanol (3×200 mL) and heptane (3×200 mL)
  5. customDry the cake on the
  6. filtrationfilter

Sources & evidence

ORD record
ord-6f69ed574e6f414fa33d465b63d88bf2
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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