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

HRID 419645Notes

Reaction equation

HRID 419645 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:47])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:18]=[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]3[C:25]=2[C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32]C3C=CC(OC4CCNCC4)=CC=3C)[N:27]=2)[CH:12]=1.[CH3:48][O:49][C:50]1[CH:56]=[C:55]([N:57]2[CH2:62][CH2:61][N:60]([S:63]([CH3:66])(=[O:65])=[O:64])[CH2:59][CH2:58]2)[CH:54]=[CH:53][C:51]=1N.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:78]([OH:83])[C:79](F)(F)F.N>CO.C(Cl)Cl>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[NH:9][C:10](=[O:47])[C:11]1[CH:12]=[C:13]([C:17]2[N:18]=[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]3[C:25]=2[C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:51]3[CH:53]=[CH:54][C:55]([N:57]4[CH2:62][CH2:61][N:60]([S:63]([CH3:66])(=[O:65])=[O:64])[CH2:59][CH2:58]4)=[CH:56][C:50]=3[O:49][CH3:48])[N:27]=2)[CH:14]=[CH:15][C:16]=1[O:83][CH2:78][CH3:79]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 64092,2,2-TrifluoroethanolHCID 59452825N-(2,6-difluorophenyl)-3-[3-(2-{[2-methyl-4-(4-piperidinyloxy)phenyl]-amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamideHCID 598602722-(Methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]aniline

Product 1

HCID 59452808N-(2,6-difluorophenyl)-2-(ethyloxy)-5-{3-[2-({2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 56%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (100 mg, 0.2 mmol), 2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]aniline (51 mg, 0.18 mmol), and p-toluenesulfonicacid (90 mg, 0.47 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 (75 mg, 0.099 mmol, 56%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.74 (s, 1H), 9.37 (s, 1H), 8.48 (s, 1H), 8.21 (d, J=5.13 Hz, 1H), 8.04 (d, J=1.83 Hz, 1H), 7.74 (dd, J=8.61, 2.38 Hz, 1H), 7.69 (d, J=8.80 Hz, 1H), 7.42-7.49 (m, 2H), 7.34-7.40 (m, 1H), 7.26 (d, J=8.80 Hz, 1H), 7.19 (t, J=8.07 Hz, 2H), 6.96 (t, J=7.15 Hz, 1H), 6.73 (d, J=2.57 Hz, 1H), 6.50-6.56 (m, 2H), 4.26 (q, J=6.97 Hz, 2H), 3.81 (s, 3H), 3.25 (br. s., 8H), 2.92 (s, 3H), 1.43 (t, J=6.97 Hz, 3H); MS (ESI): 755 [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-594da53ac1f744a1be7598b910ac6c05
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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