Hydrochloric Acid → N-(2,6-difluorophenyl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-[(1-methylethyl)oxy]benzamide

HRID 419622Notes

Reaction equation

HRID 419622 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][CH:35]([CH3:37])[CH3:36])=[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.[CH2:38]([O:40][C:41]1[CH:47]=[C:46]([N:48]2[CH2:53][CH2:52][CH:51]([CH2:54][CH2:55][S:56]([CH3:59])(=[O:58])=[O:57])[CH2:50][CH2:49]2)[C:45]([CH3:60])=[CH:44][C:42]=1[NH2:43])[CH3:39].Cl>FC(F)(F)CO>[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:43][C:42]3[CH:44]=[C:45]([CH3:60])[C:46]([N:48]4[CH2:53][CH2:52][CH:51]([CH2:54][CH2:55][S:56]([CH3:59])(=[O:58])=[O:57])[CH2:50][CH2:49]4)=[CH:47][C:41]=3[O:40][CH2:38][CH3:39])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH:35]([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 594527752-(Ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}anilineHCID 59452852HCID 59452852, compound

Product 1

HCID 59452612N-(2,6-difluorophenyl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-[(1-methylethyl)oxy]benzamideYield 24%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
180 °C

Procedure

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-[(1-methylethyl)oxy]benzamide (Intermediate Example 7) (0.13 g, 0.25 mmol) and 2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (0.087 g, 0.25 mmol) in 2,2,2-trifluoroethanol (1.5 mL) was added HCl (4M in dioxane) (0.13 mL, 0.50 mmol). The reaction was heated to 180° C. for 40 min in a microwave. The reaction was determined to be complete by HPLC. The reaction mixture was quenched with saturated NaHCO3 and sequentially extracted with DCM and EtOAc. The organic layer was dried (MgSO4), filtered, and rotovapped down. Purification by flash chromatography provided the title compound (0.05 g, 0.06 mmol, 24%). 1H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 9.36 (d, J=5.9 Hz, 1H), 8.37 (s, 1H), 8.28 (d, J=4.9 Hz, 1H), 8.09 (br. s., 1H), 7.74 (dd, J=14.1, 8.9 Hz, 2H), 7.56 (s, 1H), 7.27-7.52 (m, 3H), 7.21 (t, J=7.9 Hz, 2H), 6.96 (t, J=6.6 Hz, 1H), 6.75 (s, 1H), 6.63 (d, J=4.8 Hz, 1H), 4.79-4.97 (m, 1H), 4.07 (q, J=6.7 Hz, 2H), 3.12-3.24 (m, 2H), 3.05 (d, J=11.1 Hz, 2H), 2.98 (s, 3H), 2.61 (t, 2H), 2.14 (s, 3H), 1.62-1.87 (m, 4H), 1.17-1.59 (m, 12H). MS (M+H, ES+) 824.

Workup

  1. customThe reaction mixture was quenched with saturated NaHCO3
  2. extractionsequentially extracted with DCM and EtOAc
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customPurification by flash chromatography

Sources & evidence

ORD record
ord-c91c6c8de7624707ab53320cd0dd1e22
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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