Trifluoroacetic acid → 6-Ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(pyrrolidin-3-yloxy)pyrazine-2-carboxamide

HRID 1526193Notes

Reaction equation

HRID 1526193 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([CH2:37][CH3:38])[C:7]([O:24][CH:25]2[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26]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)=[CH:13][CH:12]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCCl>[CH2:37]([C:6]1[N:5]=[C:4]([C:1]([NH2:2])=[O:3])[C:9]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([N:17]3[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]3)=[CH:15][CH:16]=2)=[N:8][C:7]=1[O:24][CH:25]1[CH2:29][CH2:28][NH:27][CH2:26]1)[CH3:38]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117667557Tert-butyl 3-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazin-2-yl)oxy]pyrrolidine-1-carboxylate

Product 1

HCID 897091506-Ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(pyrrolidin-3-yloxy)pyrazine-2-carboxamideYield 73.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of tert-butyl 3-[(5-carbamoyl-3-ethyl-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazin-2-yl)oxy]pyrrolidine-1-carboxylate (355 mg) and 1,2-dichloroethane (6 mL) was added trifluoroacetic acid (2 mL) under ice-cooling, followed by stirring at room temperature for 12 hours. The reaction mixture was concentrated, then diluted with chloroform, and neutralized with a 10% aqueous potassium carbonate solution. After extraction with chloroform, the organic phase was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1), and dried under reduced pressure to obtain 6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(pyrrolidin-3-yloxy)pyrazine-2-carboxamide (212 mg) as a yellow solid.

Workup

  1. temperaturecooling
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with chloroform
  4. extractionAfter extraction with chloroform
  5. dry with materialthe organic phase was dried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1)
  8. customdried under reduced pressure

Sources & evidence

ORD record
ord-3564d52450744d2e9393203348744fb3
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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