Hydrochloric Acid → HCID 136334377, compound

HRID 2064629Notes

Reaction equation

HRID 2064629 reaction equation
[CH2:1]([C:3]1[C:22]([CH3:23])=[CH:21][C:6]2[NH:7][C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]#[N:20])[CH:17]=4)[NH:12][N:11]=3)=[N:9][C:5]=2[CH:4]=1)[CH3:2].C(=O)([O-])[O-:25].[Na+].[Na+].[ClH:30]>C(O)(=O)C>[ClH:30].[ClH:30].[CH2:1]([C:3]1[C:22]([CH3:23])=[CH:21][C:6]2[NH:7][C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]([NH2:20])=[O:25])[CH:17]=4)[NH:12][N:11]=3)=[N:9][C:5]=2[CH:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 136334324HCID 136334324, compound

Product 1

HCID 136334377HCID 136334377, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

A stirred suspension of 3-(5-ethyl-6-methyl-1H-benzoimidazol-2-yl)-1H-indazole-5-carbonitrile [100 mg, Example 235(an)] in acetic acid (1 ml) and concentrated hydrochloric acid (1 ml) was heated at 80° C. for 30 minutes and then at 100° C. for 4 hours. The reaction was cooled to ambient temperature and stirred for 16 hours. The reaction was then heated at 80° C. for 2.5 hours and then at 100° C. for 2 hours. The reaction mixture was cooled to ambient temperature and neutralized with aqueous sodium carbonate solution. The resulting white precipitate was collected by filtration and the aqueous layer was extracted with ethyl acetate, combined with the precipitate and concentrated in vacuo. The residue was taken up in methanol, transferred to a solid phase cartridge containing MP-carbonate resin (100 mg) and shaken for 16 hours. The reaction was then filtered, the resin washed with methanol and the combined organic layers concentrated in vacuo. The residue was triturated with diethyl ether, taken up in methanol and acidified with 4M hydrogen chloride in 1,4-dioxane. The solvent was removed in vacuo to give 3-(5-ethyl-6-methyl-1H-benzoimidazol-2-yl)-1H-indazole-5-carboxylic acid amide dihydrochloride (58 mg) as a pale brown solid. LC-MS (METHOD M): RT=9.40 minutes, 320 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. temperatureThe reaction was then heated at 80° C. for 2.5 hours
  3. waitat 100° C. for 2 hours
  4. filtrationThe resulting white precipitate was collected by filtration
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. concentrationconcentrated in vacuo
  7. additioncontaining MP-carbonate resin (100 mg)
  8. stirringshaken for 16 hours
  9. filtrationThe reaction was then filtered
  10. washthe resin washed with methanol
  11. concentrationthe combined organic layers concentrated in vacuo
  12. customThe residue was triturated with diethyl ether
  13. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-f7854eb565b74aa1ae49780a912d285b
Source dataset
uspto-grants-2012_10
Patent number
US08288425B2

Reaction notes

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