Ammonia → N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl]phenyl)amino}-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide

HRID 419570Notes

Reaction equation

HRID 419570 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:47]2[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH2:49][CH2:48]2)=[CH:40][C:41]([O:45][CH3:46])=[C:42]([CH:44]=1)[NH2:43])[CH3:37].Cl.O1CCOCC1.N>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:38]([CH2:36][CH3:37])[C:39]([N:47]4[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH2:49][CH2:48]4)=[CH:40][C:41]=3[O:45][CH3:46])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 59452956HCID 59452956, compound

Product 1

HCID 59452582N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl]phenyl)amino}-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamideYield 38%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
180 °C

Procedure

In a microwave vial with septum cap, 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (0.246 g, 0.5 mmol) and 5-ethyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}aniline (0.171 g, 0.5 mmol) were taken up in 1,1,1-trifluoroethanol (3 mL) and 4M HCl in dioxane (0.25 mL, 1.0 mmol) was added. The vial was sealed and heated in the microwave at 180° C. for 40 min. Reaction was complete by MS, it was cooled rt, neutralized with 7N NH3 in MeOH, and concentrated in vacuo onto silica gel and flash chromatographed. The desired fractions were combined and concentrated and the resulting solid was triturated with diethyl ether, filtered and air dried to give the title compound (0.150 g, 0.19 mmol, 38%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.78 (s, 1H), 9.34 (dd, J=3.1, 2.2 Hz, 1H), 8.49 (s, 1H), 8.24 (d, J=5.1 Hz, 1H), 8.11 (d, J=1.3 Hz, 1H), 7.78 (dd, J=8.9, 1.4 Hz, 1H), 7.70 (d, J=9.0 Hz, 1H), 7.54 (s, 1H), 7.33-7.50 (m, 2H), 7.28 (d, J=8.8 Hz, 1H), 7.18 (t, J=8.1 Hz, 2H), 6.94 (t, J=6.6 Hz, 1H), 6.83 (s, 1H), 6.57 (d, J=4.9 Hz, 1H), 3.98 (s, 3H), 3.80 (s, 3H), 3.28-3.40 (m, 2H), 3.06 (s, 3 H), 2.82-2.92 (m, 4H), 2.77 (t, J=6.5 Hz, 2H), 2.50-2.69 (m, 6H), 1.08 (q, J=7.0 Hz, 3H). MS (M+H, ES+) 797.

Workup

  1. customIn a microwave vial with septum cap
  2. customThe vial was sealed
  3. customReaction
  4. temperaturewas cooled rt
  5. concentrationconcentrated in vacuo onto silica gel and flash
  6. customchromatographed
  7. concentrationconcentrated
  8. customthe resulting solid was triturated with diethyl ether
  9. filtrationfiltered
  10. customair dried

Sources & evidence

ORD record
ord-7949a16ac8804c26a69edecaf012aee9
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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