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

HRID 419639Notes

Reaction equation

HRID 419639 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]([S:52]([CH3:55])(=[O:54])=[O:53])[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[CH2:51][CH2:50][N:49]([S:52]([CH3:55])(=[O:54])=[O:53])[CH2:48][CH2:47]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 594527885-Methyl-2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]aniline

Product 1

HCID 59453006N-(2,6-difluorophenyl)-5-{3-[2-({5-methyl-2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}-2-(methyloxy)benzamideYield 37%

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), 5-methyl-2-(methyloxy)-4-[4-(methylsulfonyl)-1-piperazinyl]aniline (53 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 (50 mg, 0.066 mmol, 37%). 1H NMR (400 MHz, DMSO-d6) d ppm 9.78 (s, 1H), 9.38 (d, J=6.97 Hz, 1H), 8.49 (s, 1H), 8.24 (d, J=5.13 Hz, 1H), 8.10 (d, J=2.20 Hz, 1H), 7.78 (dd, J=8.80, 2.20 Hz, 1H), 7.70 (d, J=8.80 Hz, 1H), 7.54 (s, 1H), 7.42-7.48 (m, 1H), 7.34-7.42 (m, 1H), 7.28 (d, J=8.80 Hz, 1H), 7.18 (t, J=8.07 Hz, 2H), 6.92-7.01 (m, 1H), 6.83 (s, 1H), 6.57 (d, J=5.13 Hz, 1H), 3.98 (s, 3H), 3.81 (s, 3H), 3.24-3.30 (m, 4H), 2.95-2.99 (m, 4H), 2.94 (s, 3H), 2.17 (s, 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-5f47d07137e04b5b9d11df98b662ed23
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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