2-Methoxyaniline → HCID 66642846, compound

HRID 869278Notes

Reaction equation

HRID 869278 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([CH2:38][CH3:39])[C:7]([NH:28][CH:29]2[CH2:34][CH2:33][CH:32]([C:35](O)=[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].[CH3:40][O:41][C:42]1[C:43]([NH2:48])=[CH:44][CH:45]=[CH:46][CH:47]=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[CH2:38]([C:6]1[N:5]=[C:4]([C:1]([NH2:2])=[O:3])[C:9]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[C:13]([C:24]([F:25])([F:26])[F:27])[CH:12]=2)=[N:8][C:7]=1[NH:28][CH:29]1[CH2:34][CH2:33][CH:32]([C:35](=[O:36])[NH:48][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[O:41][CH3:40])[CH2:31][CH2:30]1)[CH3:39]

Participants

7

Reactant 5

HCID 70002-MethoxyanilineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66642976HCID 66642976, compound

Product 1

HCID 66642846HCID 66642846, compoundYield 44.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]amino}pyrazin-2-yl)amino]cyclohexanecarboxylic acid (Example 436) (62 mg), o-anisidine (42 mg) and DMF (2 mL), 1-hydroxy-1H-benzotriazole monohydrate (46 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (65 mg) were added and stirred at room temperature for 7 hours. The reaction liquid was poured into saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride sequentially and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol) to give 6-ethyl-5-({4-[(2-methoxy-phenyl)carbamoyl]cyclohexyl}amino)-3-{[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]amino}pyrazine-2-carboxamide (33 mg) as a yellow powder.

Workup

  1. additionwere added
  2. customThe reaction liquid
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water and saturated aqueous sodium chloride sequentially
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol)

Sources & evidence

ORD record
ord-7abf66213d454ad3b73d281e1504d7f0
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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