Hydrochloric Acid → 4-({1-[(3-Fluorophenyl)methyl]-1H-indazol-5-yl}amino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid

HRID 2212498Notes

Reaction equation

HRID 2212498 reaction equation
C([O:3][C:4]([C:6]1[C:7]([CH3:33])=[C:8]2[N:13]([CH:14]=1)[N:12]=[CH:11][N:10]=[C:9]2[NH:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[N:21]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1)[N:20]=[CH:19]2)=[O:5])C.[OH-].[Na+].Cl>C1COCC1.CO>[F:32][C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=1)[CH2:25][N:21]1[C:22]2[C:18](=[CH:17][C:16]([NH:15][C:9]3[C:8]4=[C:7]([CH3:33])[C:6]([C:4]([OH:5])=[O:3])=[CH:14][N:13]4[N:12]=[CH:11][N:10]=3)=[CH:24][CH:23]=2)[CH:19]=[N:20]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 11655192HCID 11655192, compound

Product 1

HCID 219664944-({1-[(3-Fluorophenyl)methyl]-1H-indazol-5-yl}amino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acidYield 88%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A flask equipped with mechanical stirrer was charged with 4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester (19) (1 equiv), THF (4 volumes) and MeOH (2.5 volumes). The suspension was cooled to 5 C and 50% NaOH (5.3 equiv.) solution was slowly added maintaining the temperature below 15° C. The resulting solution was warmed to 60° C. for 4 h, and then cooled to 25° C. THF (7 volumes) was charged to the reaction and concentrated HCl (9.95 equiv.) was slowly added maintaining the temperature below 35° C. to pH 3. The resulting slurry was stirred at ambient temperature overnight, and then filtered. The filter cake was washed with H2O (3×5 volumes) and dried on the filter for 1 h. The filter cake was washed with heptane (1×1 volume) and dried under vacuum at 50° C. to afford the product in 88% yield as an off-white solid.

Workup

  1. customA flask equipped with mechanical stirrer
  2. additionwas slowly added
  3. temperaturemaintaining the temperature below 15° C
  4. temperaturecooled to 25° C
  5. additionwas slowly added
  6. temperaturemaintaining the temperature below 35° C. to pH 3
  7. filtrationfiltered
  8. washThe filter cake was washed with H2O (3×5 volumes)
  9. customdried on the
  10. filtrationfilter for 1 h
  11. washThe filter cake was washed with heptane (1×1 volume)
  12. customdried under vacuum at 50° C.
  13. customto afford the product in 88% yield as an off-white solid

Sources & evidence

ORD record
ord-22d15f97a87b4ee793395a6e6a3cbaf5
Source dataset
uspto-grants-2006_09
Patent number
US07102001B2

Reaction notes

Loading…