Diisopropylamine → 4-[2-Fluoro-4-(2-pyridin-3-yl-benzoylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 2196183Notes

Reaction equation

HRID 2196183 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=2[F:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]2[CH:36]=[CH:35][CH:34]=[CH:33][C:29]=2[C:30](O)=[O:31])[CH:23]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(NC(C)C)(C)C>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:30](=[O:31])[C:29]3[CH:33]=[CH:34][CH:35]=[CH:36][C:28]=3[C:24]3[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=3)=[CH:16][C:15]=2[F:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 27605052-(Pyridin-3-yl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 162036301,1-Dimethylethyl 4-(4-amino-2-fluorophenyl)-1-piperazinecarboxylate

Product 1

HCID 669318584-[2-Fluoro-4-(2-pyridin-3-yl-benzoylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-Amino-2-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (1.00 g, 3.4 mmol) and 2-pyrid-3-yl benzoic acid (0.70 g, 3.7 mmol) in DMF (10 mL) was added HATU (1.42 g, 3.7 mmol) and diisopropylamine (0.65 mL, 3.7 mmol). After stirring at room temperature for 18 h, the reaction mixture was diluted with EtOAc (100 mL) and washed with H2O (4×50 mL). The organic extracts were combined, dried (Na2SO4), and the solvent was evaporated under reduced pressure. Chromatography of the resulting residue (SiO2: EtOAc:Hex) yielded 4-[2-fluoro-4-(2-pyridin-3-yl-benzoylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester which was further dissolved in MeOH (20 mL) and 4N HCl in dioxanes. After stirring for 5 h, the reaction mixture was concentrated down, neutralized with 1N NaOH, and extracted with EtOAc (3×75mL). The organic extracts were combined, dried (Na2SO4), and the solvent was evaporated under reduced pressure to yield the title compound.

Workup

  1. washwashed with H2O (4×50 mL)
  2. dry with materialdried (Na2SO4)
  3. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-7d22b536dda2404ba9bff137375abc94
Source dataset
uspto-grants-2012_12
Patent number
US08338426B2

Reaction notes

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