Hydrochloric Acid → N-(2,6-difluorophenyl)-5-[3-(2-{[4-{5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)benzamide

HRID 419338Notes

Reaction equation

HRID 419338 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][N:37]([CH2:39][C:40]1[O:44][C:43]([C:45]2[CH:51]=[CH:50][C:48]([NH2:49])=[C:47]([O:52][CH3:53])[CH:46]=2)=[N:42][N:41]=1)[CH3:38].Cl>C(O)C(F)(F)F>[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:49][C:48]3[CH:50]=[CH:51][C:45]([C:43]4[O:44][C:40]([CH2:39][N:37]([CH3:36])[CH3:38])=[N:41][N:42]=4)=[CH:46][C:47]=3[O:52][CH3:53])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 594529104-{5-[(Dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}-2-(methyloxy)aniline

Product 1

HCID 59452889N-(2,6-difluorophenyl)-5-[3-(2-{[4-{5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)benzamideYield 51%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
85 °C

Procedure

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (0.12 g, 0.25 mmol) and 4-{5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}-2-(methyloxy)aniline (0.069 g, 0.28 mmol) in trifluoroethanol (5 mL) was added HCl (0.050 mL, 4 M in dioxane, 0.20 mmol). The reaction was heated at 85° C. for 48 hours. Purification by flash chromatography followed by trituration with diethyl ether provided the title compound (0.089 g, 0.12 mmol, 51%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.23 (s, 6H), 3.76 (s, 2H), 3.96 (d, J=4.6 Hz, 6H), 6.76 (d, J=4.9 Hz, 1H), 7.03 (t, J=6.9 Hz, 1H), 7.15 (t, J=8.1 Hz, 2H), 7.26 (d, J=8.2 Hz, 1H), 7.30-7.40 (m, 1H), 7.42-7.50 (m, 1H), 7.51-7.59 (m, 2H), 7.71 (d, J=9.2 Hz, 1H), 7.78 (d, J=8.8 Hz, 1H), 8.10 (br. s., 1H), 8.35 (d, J=8.6 Hz, 1H), 8.39 (d, J=5.5 Hz, 1H), 8.69 (br. s., 1H), 9.44 (d, J=6.8 Hz, 1H), 9.74 (s, 1H). MS (M+H, ES+) 704.

Workup

  1. customPurification by flash chromatography

Sources & evidence

ORD record
ord-9f010f1a5c16438ba70e15450db11c9b
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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