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

HRID 419660Notes

Reaction equation

HRID 419660 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][C:37]1[C:38]([N:46]2[CH2:51][CH2:50][N:49]([CH2:52][CH2:53][O:54][CH3:55])[CH2:48][CH2:47]2)=[CH:39][C:40]([O:44][CH3:45])=[C:41]([CH:43]=1)[NH2:42].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:42][C:41]3[CH:43]=[C:37]([CH3:36])[C:38]([N:46]4[CH2:47][CH2:48][N:49]([CH2:52][CH2:53][O:54][CH3:55])[CH2:50][CH2:51]4)=[CH:39][C:40]=3[O:44][CH3:45])[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 594528205-Methyl-2-(methyloxy)-4-{4-[2-(methyloxy)ethyl]-1-piperazinyl}aniline

Product 1

HCID 59452958N-(2,6-difluorophenyl)-5-(3-{2-[(5-methyl-2-(methyloxy)-4-{4-[2-(methyloxy)ethyl]-1-piperazinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamideYield 47%

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) (200 mg, 0.4 mmol), 5-methyl-2-(methyloxy)-4-{4-[2-(methyloxy)ethyl]-1-piperazinyl}aniline (Example 241, step B) (102 mg, 0.37 mmol) and p-toluenesulfonicacid (185 mg, 0.98 mmol) were weighed into a 20 mL vial. 2 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 (125 mg, 0.17 mmol, 47%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.75 (s, 1H), 9.33 (s, 1H), 8.43 (s, 1H), 8.20 (d, J=5.31 Hz, 1H), 8.07 (d, J=1.83 Hz, 1H), 7.74 (dd, J=8.70, 1.74 Hz, 1H), 7.66 (d, J=8.97 Hz, 1H), 7.45 (s, 1H), 7.33-7.45 (m, 2H), 7.25 (d, J=8.79 Hz, 1H), 7.15 (t, J=8.06 Hz, 2H), 6.89-6.95 (m, 1H), 6.74 (s, 1H), 6.53 (d, J=5.13 Hz, 1H), 3.95 (s, 3H), 3.76 (s, 3H), 3.43 (t, J=5.77 Hz, 2H), 3.21 (s, 3H), 2.83 (t, J=4.40 Hz, 4H), 2.47-2.58 (m, 6H), 2.11 (s, 3H); MS (ESI): 735 [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-02a31abe136741df9709e9a018190b5e
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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