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

HRID 419646Notes

Reaction equation

HRID 419646 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.[CH3:36][O:37][C:38]1[CH:44]=[C:43]([N:45]2[CH2:50][CH2:49][N:48]([S:51]([CH3:54])(=[O:53])=[O:52])[CH2:47][CH2:46]2)[CH:42]=[CH:41][C:39]=1[NH2:40].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)C(F)(F)F.N>CO.C(Cl)Cl>[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:40][C:39]3[CH:41]=[CH:42][C:43]([N:45]4[CH2:46][CH2:47][N:48]([S:51]([CH3:54])(=[O:53])=[O:52])[CH2:49][CH2:50]4)=[CH:44][C:38]=3[O:37][CH3:36])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 64092,2,2-TrifluoroethanolHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 598602722-(Methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]aniline

Product 1

HCID 59452983N-(2,6-difluorophenyl)-2-(methyloxy)-5-{3-[2-({2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 69%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

5-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (100 mg, 0.2 mmol), 2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]aniline (Example 232, step B) (51 mg, 0.18 mmol), and p-toluenesulfonicacid (93 mg, 0.49 mmol) were weighed into a 20 mL vial. 1 mL of trifluoroethanol was added and the mixture was heated to 100° C. for 72 h. 2 mL of 2 N ammonia in MeOH was added. The solvent was rotovaped down. The residue was taken up in 3 mL of DCM. 1 g of silica gel was added. The solvent was rotovaped down and the pre-absorbed solids were purified by flash chromatography to give the title compound (96 mg, 0.12 mmol, 69%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.78 (s, 1H), 9.37 (s, 1H), 8.48 (s, 1H), 8.21 (d, J=5.13 Hz, 1H), 8.10 (d, J=1.83 Hz, 1H), 7.77 (dd, J=8.61, 2.02 Hz, 1H), 7.69 (d, J=8.80 Hz, 1H), 7.36-7.48 (m, 3H), 7.28 (d, J=8.43 Hz, 1H), 7.18 (t, J=8.07 Hz, 2H), 6.96 (t, J=6.78 Hz, 1H), 6.73 (d, J=2.20 Hz, 1H), 6.49-6.57 (m, 2H), 3.98 (s, 3H), 3.81 (s, 3H), 3.25 (br. s., 8H), 2.92 (s, 3H); MS (ESI): 741 [M+H]+.

Workup

  1. addition1 g of silica gel was added
  2. customthe pre-absorbed solids were purified by flash chromatography

Sources & evidence

ORD record
ord-d1ee3b196254480da3abbf6e7538f781
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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