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

HRID 419647Notes

Reaction equation

HRID 419647 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]=[C:19]([CH:31]=[CH:32][CH:33]=2)[C:20]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[O:21])[CH:5]=[CH:4][N:3]=1.[CH3:34][O:35][C:36]1[CH:42]=[C:41]([N:43]2[CH2:48][CH2:47][N:46]([S:49]([CH3:52])(=[O:51])=[O:50])[CH2:45][CH2:44]2)[CH:40]=[CH:39][C:37]=1[NH2:38].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)C(F)(F)F.N>CO.C(Cl)Cl>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[NH:22][C:20](=[O:21])[C:19]1[CH:31]=[CH:32][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:38][C:37]3[CH:39]=[CH:40][C:41]([N:43]4[CH2:44][CH2:45][N:46]([S:49]([CH3:52])(=[O:51])=[O:50])[CH2:47][CH2:48]4)=[CH:42][C:36]=3[O:35][CH3:34])[N:7]=2)[CH:18]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 64092,2,2-TrifluoroethanolHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamideHCID 598602722-(Methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]aniline

Product 1

HCID 59452791N-(2,6-difluorophenyl)-3-{3-[2-({2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

3-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamide (Intermediate Example 1) (100 mg, 0.22 mmol), 2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]aniline (Example 232, step B) (51 mg, 0.18 mmol), and p-toluenesulfonicacid (99 mg, 0.52 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 (92 mg, 0.13 mmol, 73%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.24 (s, 1H), 9.40 (s, 1H), 8.49 (s, 1H), 8.33 (s, 1H), 8.21 (d, J=5.13 Hz, 1H), 8.05 (d, J=7.70 Hz, 1H), 7.82 (d, J=7.70 Hz, 1H), 7.73 (d, J=8.80 Hz, 1H), 7.61 (t, J=7.70 Hz, 1H), 7.43-7.49 (m, 2H), 7.35-7.43 (m, 1H), 7.16-7.24 (m, 2H), 6.99 (t, J=6.78 Hz, 1H), 6.73 (d, J=2.20 Hz, 1H), 6.52 (dd, J=8.62, 2.38 Hz, 1H), 6.48 (d, J=5.13 Hz, 1H), 3.81 (s, 3H), 3.25 (br. s., 8H), 2.92 (s, 3H); MS (ESI): 711 [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-1282e65b48f54fb4a0b932cb33657b47
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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