Hydrochloric Acid → HCID 59452676, compound

HRID 419321Notes

Reaction equation

HRID 419321 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][N:35]1[CH:39]=[C:38]([C:40]2[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=2)[NH2:43])[CH:37]=[N:36]1.Cl.C([O-])(O)=O.[Na+]>C(O)C(F)(F)F.CCOC(C)=O>[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:43][C:42]3[CH:44]=[CH:45][CH:46]=[C:40]([C:38]4[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=4)[CH:41]=3)[N:7]=2)[CH:18]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 288753303-(1-Methyl-1H-pyrazol-4-yl)anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 59452676HCID 59452676, compoundYield 63.4%

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

3-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (0.100 g, 0.217 mmol) and 3-(1-methyl-1H-pyrazol-4-yl)aniline (0.0563 g, 0.325 mmol) was dissolved in 4 mL of trifluoroethanol with stirring. HCl (0.11 mL, 4N in dioxane, 0.44 mmol) was added, and the vessel was sealed. The reaction was heated to 80° C. for 4.5 days and cooled to rt. The reaction was poured into half-saturated aqueous NaHCO3 solution and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography afforded a solid that was triturated with diethyl ether to yield 0.0823 g (63%) of the desired compound. 1H NMR (400 MHz, DMSO-d6) δ 10.21 (s, 1H), 9.73 (s, 1H), 9.52 (d, J=5.1 Hz, 1H), 8.37-8.30 (m, 2H), 8.03 (d, J=7.3 Hz, 1H), 7.94 (s, 1H), 7.91 (s, 1H), 7.83 (d, J=7.3 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.69 (s, 1H), 7.59 (t, J=7.7 Hz, 1H), 7.54-7.43 (m, 2H), 7.42-7.32 (m, 1H), 7.26-7.11 (m, 4H), 7.00-6.92 (m, 1H), 6.61 (d, J=5.3 Hz, 1H), 3.80 (s, 3H). MS (M+H, ES+) 599.

Workup

  1. customthe vessel was sealed
  2. temperaturecooled to rt
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. extractionThe combined aqueous layers were extracted with EtOAc
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography
  10. customafforded a solid
  11. customthat was triturated with diethyl ether

Sources & evidence

ORD record
ord-c8f2e1b73e7c4caf97aa8f8f41b5089b
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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