Hydrochloric Acid → HCID 66642976, compound

HRID 869277Notes

Reaction equation

HRID 869277 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([CH2:39][CH3:40])[C:7]([NH:28][CH:29]2[CH2:34][CH2:33][CH:32]([C:35]([O:37]C)=[O:36])[CH2:31][CH2:30]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[C:13]([C:24]([F:27])([F:26])[F:25])[CH:12]=1)(=[O:3])[NH2:2].C1COCC1.[OH-].[Na+].Cl>CO>[C:1]([C:4]1[N:5]=[C:6]([CH2:39][CH3:40])[C:7]([NH:28][CH:29]2[CH2:34][CH2:33][CH:32]([C:35]([OH:37])=[O:36])[CH2:31][CH2:30]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]2)=[C:13]([C:24]([F:25])([F:27])[F:26])[CH:12]=1)(=[O:3])[NH2:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 66642857HCID 66642857, compound

Product 1

HCID 66642976HCID 66642976, compoundYield 38.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of methyl 4-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]amino}pyrazin-2-yl)amino]cyclohexanecarboxylate (Example 435) (126 mg), THF (2 mL) and methanol (2 mL), 10% aqueous sodium hydroxide (1 mL) was added and heated under reflux for 2 hours. To the reaction liquid, 10% hydrochloric acid was added to give a pH of about 7, and the resulting solid was collected by filtration. This solid was purified by silica gel column chromatography (eluent; chloroform:methanol) to give 4-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]amino}pyrazin-2-yl)amino]cyclohexanecarboxylic acid (Example 436) (47 mg), which was a low-polarity product, as a light yellow white powder and 4-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]amino}pyrazin-2-yl)amino]cyclohexanecarboxylic acid (Example 437) (59 mg), which was a high-polarity product, as a light yellow powder.

Workup

  1. additionwas added
  2. temperatureheated
  3. temperatureunder reflux for 2 hours
  4. additionwas added
  5. customto give a pH of about 7
  6. filtrationthe resulting solid was collected by filtration
  7. customThis solid was purified by silica gel column chromatography (eluent; chloroform:methanol)

Sources & evidence

ORD record
ord-6ad7547db4b44d3982f9350076a8db42
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

Loading…