Potassium Carbonate → (3-{6-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-ylamino}-3-phenyl-propyl)-carbamic acid tert-butyl ester

HRID 1186514Notes

Reaction equation

HRID 1186514 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][N:15]=[C:16]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)[C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:4][CH:3]=1.[C:24]([O:28][C:29](=[O:41])[NH:30][CH2:31][CH2:32][CH:33]([NH2:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([CH3:27])([CH3:26])[CH3:25].CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:24]([O:28][C:29](=[O:41])[NH:30][CH2:31][CH2:32][CH:33]([NH:40][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][N:15]=[C:16]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)[C:11]3=[N:10][CH:9]=2)[N:7]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 57826906Tert-butyl 3-amino-3-phenylpropylcarbamateHCID 86670919HCID 86670919, compound

Product 1

HCID 68227060(3-{6-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-ylamino}-3-phenyl-propyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 3-(6-bromo-pyridin-2-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine (from Example 39 supra) (0.56 g, 1.5 mmol), (3-amino-3-phenyl-propyl)-carbamic acid tert-butyl ester (from Example 53 supra) (0.45 g, 1.8 mmol), Pd2(dba)3 (90 mg), Davephos (120 mg), K2CO3 (0.25 g, 1.8 mmol) in dioxane (60 mL) in a sealed tube was bubbled with N2 for several minutes and then heated under N2 at 130° C. for 15 hours. The solution was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified first by chromatography (CH2Cl2:CH3OH, 100:1) then by preparative-HPLC to give (3-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-ylamino}-3-phenyl-propyl)-carbamic acid tert-butyl ester. (Yield 44 mg, 5.4%). LC-MS: [M+H]+ 543.

Workup

  1. customwas bubbled with N2 for several minutes
  2. temperatureThe solution was then cooled to room temperature
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified first by chromatography (CH2Cl2:CH3OH, 100:1)

Sources & evidence

ORD record
ord-3d606502e0a24169aa6075a828b07d47
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

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