(4-Aminophenoxy)benzene → HCID 57708276, compound

HRID 1053223Notes

Reaction equation

HRID 1053223 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:3]=1.[O:22]([C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[O:22]([C:29]1[CH:30]=[CH:31][C:32]([NH:33][C:2]2[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH:9]3[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]3)[CH:3]=2)=[CH:34][CH:35]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 8764(4-Aminophenoxy)benzeneHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 22309474tert-Butyl 3-((6-chloropyrimidin-4-yl)amino)piperidine-1-carboxylate

Product 1

HCID 57708276HCID 57708276, compoundYield 40.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 3-(6-chloropyrimidin-4-ylamino)piperidine-1-carboxylate (0.15 g, 0.48 mmol), 4-phenoxyaniline (0.089 g, 0.48 mmol), Pd(OAc)2 (0.010 g, 0.048 mmol), BINAP (0.014 g, 0.024 mmol) and Cs2CO3 (0.39 g, 1.2 mmol) in degassed toluene (toluene was purged with N2 for 15 min) was heated for 12 h at 100° C. under N2 atmosphere. The reaction mixture was cooled, was diluted with EtOAc (20 mL) and was washed with water (4 mL) and brine (2 mL) and was dried over Na2SO4. The crude product obtained was purified by column chromatography (SiO2, 230-400, chloroform/methanol:99/1) to give tert-butyl 3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)piperidine-1-carboxylate (90 mg, 40.9%) as a light yellow solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwas washed with water (4 mL) and brine (2 mL)
  3. dry with materialwas dried over Na2SO4
  4. customThe crude product obtained
  5. customwas purified by column chromatography (SiO2, 230-400, chloroform/methanol:99/1)

Sources & evidence

ORD record
ord-7f742596bf7e483abd0d425f400b5e67
Source dataset
uspto-grants-2016_07
Patent number
US09393246B2

Reaction notes

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