Hydrochloric Acid → n-(2,6-Difluorophenyl)-5-(3-{2-[(5-ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide

HRID 419596Notes

Reaction equation

HRID 419596 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[CH:19][C:20]([O:34][CH3:35])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[CH2:36]([C:38]1[C:39]([N:48]2[CH2:53][CH2:52][CH:51]([N:54]3[CH2:59][CH2:58][N:57]([S:60]([CH3:63])(=[O:62])=[O:61])[CH2:56][CH2:55]3)[CH2:50][CH2:49]2)=[CH:40][C:41]([O:45][CH2:46][CH3:47])=[C:42]([NH2:44])[CH:43]=1)[CH3:37].Cl>C(O)C(F)(F)F>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:44][C:42]3[CH:43]=[C:38]([CH2:36][CH3:37])[C:39]([N:48]4[CH2:49][CH2:50][CH:51]([N:54]5[CH2:55][CH2:56][N:57]([S:60]([CH3:63])(=[O:62])=[O:61])[CH2:58][CH2:59]5)[CH2:52][CH2:53]4)=[CH:40][C:41]=3[O:45][CH2:46][CH3:47])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 594526865-Ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline

Product 1

HCID 59452906n-(2,6-Difluorophenyl)-5-(3-{2-[(5-ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamideYield 67.7%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
170 °C

Procedure

A mixture of 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (0.1 g, 0.203 mmol), (5-ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amine (0.083 g, 0.203 mmol) and HCl (4N,1,4-Dioxane, 0.102 mL, 0.407 mmol) in Trifluoroethanol (8 mL) was heated at 170° C. for 40 min in the microwave. LCMS analysis indicated that the starting materials had been consumed. The reaction was quenched with 7N NH3 in MeOH and then concentrated to dryness. The residue was then dissolved in DCM and concentrated onto silica gel. Purification by flash column chromatography followed by recrystallization from DCM and EtOH afforded the title compound N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide (0.119 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.79 (s, 1H), 9.27-9.38 (m, 1H), 8.40 (s, 1H), 8.28 (d, J=5.22 Hz, 1H), 8.13 (d, J=1.92 Hz, 1H), 7.80 (dd, J=8.39, 1.88 Hz, 1H), 7.72 (d, J=8.98 Hz, 1H), 7.58 (s, 1H), 7.35-7.51 (m, 2H), 7.29 (d, J=8.71 Hz, 1H), 7.14-7.25 (m, 2H), 6.88-6.98 (m, 1H), 6.81 (s, 1H), 6.60 (d, J=5.13 Hz, 1H), 4.06 (q, J=6.97 Hz, 2H), 4.00 (s, 3H), 3.07-3.15 (m, 4H), 2.98-3.06 (m, 2H), 2.87 (s, 3H), 2.60-2.74 (m, 6H), 2.52-2.59 (m, 2H), 2.36-2.46 (m, 1H), 1.80-1.87 (m, 2H), 1.50-1.67 (m, 2H), 1.26 (t, J=6.97 Hz, 3H), 1.09 (t, J=7.51 Hz, 3H). MS (M+H, ES+) 866.

Workup

  1. customhad been consumed
  2. customThe reaction was quenched with 7N NH3 in MeOH
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was then dissolved in DCM
  5. concentrationconcentrated onto silica gel
  6. customPurification by flash column chromatography
  7. customfollowed by recrystallization from DCM and EtOH

Sources & evidence

ORD record
ord-53e5032e259f4d38955350a75f40c49f
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…