tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate → 4-{-4-[5-Bromo-4-(cyclohexyl-phenyl-amino)-pyrimidin-2-ylamino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 875946Notes

Reaction equation

HRID 875946 reaction equation
[Br:1][C:2]1[C:3]([N:9]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:4][C:5](Cl)=[N:6][CH:7]=1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>O1CCOCC1.C(OCC)(=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:36]=[CH:37][C:38]([NH:41][C:5]3[N:4]=[C:3]([N:9]([CH:16]4[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]4)[C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)[C:2]([Br:1])=[CH:7][N:6]=3)=[CH:39][CH:40]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 2

HCID 11011301tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylateHCID 58299589(5-Bromo-2-chloro-pyrimidin-4-yl)-cyclohexyl-phenyl-amine

Product 1

HCID 672353454-{-4-[5-Bromo-4-(cyclohexyl-phenyl-amino)-pyrimidin-2-ylamino]-phenyl}-piperazine-1-carboxylic acid tert-butyl esterYield 33%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Compound 37 (0.42 g, 1.15 mmol) and 4-(4-amino-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (0.64 g, 2.30 mmol) were dissolved in dioxane (2 mL), and this mixture was heated at 100° C. for 24 hours. The reaction was cooled to room temperature and diluted with ethyl acetate. This mixture was washed with water and brine. The organic layer was dried with sodium sulfate and purified by flash chromatography (ethyl acetate/hexane) to give compound 38 as a yellow solid (0.23 g, 33%). 1H NMR (500 MHz, DMSO-d6) δ ppm 9.18 (1 H, s), 7.97 (1 H, s), 7.55 (2 H, d, J=10 Hz), 7.37 (2 H, m), 7.31 (1 H, m), 7.12 (2 H, m), 6.89 (2 H, d, J=10 Hz), 4.68 (1 H, m), 3.44 (4 H, m), 3.00 (4 H, m), 1.91 (2 H, d, J=10 Hz), 1.72 (2 H, d, J=10 Hz), 1.57 (1 H, d, J=10 Hz), 1.41 (9 H, s), 1.35 (2 H, m), 1.14 (2 H, m), 0.92 (1 H, m); LCMS-ESI (POS), M/Z, M+1: Found 609.2, Calculated 607.2/609.2.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. washThis mixture was washed with water and brine
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. custompurified by flash chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2926333a45894bf986b9876534fe27cf
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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