Benzylamine → Benzyl-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine

HRID 1186510Notes

Reaction equation

HRID 1186510 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.[CH2:24]([NH2:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.CC([O-])(C)C.[Na+]>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]>[CH2:24]([NH:31][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:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86670919HCID 86670919, compound

Product 1

HCID 68226504Benzyl-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine

Reagents, catalysts & solvents 2

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

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) (0.187 g, 0.5 mmol), benzylamine (0.075 g, 0.7 mmol), Pd2(dba)3 (30 mg), Davephos (40 mg), NaOtBu (70 mg, 0.73 mmol) in dioxane (20 mL) was bubbled with N2 for several minutes and then heated under N2 at reflux overnight. The solution was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified firstly by chromatography (CH2Cl2:CH3OH, 100:1), then by preparative-HPLC to give benzyl-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine. (Yield 70 mg, 35%). 1HNMR (300 MHz, CDCl3): δ 8.70 (d, 1H, J=4.5 Hz), 7.88 (s, 1H), 7.51-7.24 (m, 7H), 7.02 (d, 1H, J=7.2 Hz), 6.37 (d, 1H, J=8.1 Hz), 5.03-5.02 (m, 1H), 4.62 (d, 2H, J=3.9 Hz), 4.24 (brs, 4H), 2.61-2.58 (m, 4H), 2.36 (s, 3H). LC-MS: [M+H]+ 400.

Workup

  1. customwas bubbled with N2 for several minutes
  2. temperatureheated under N2
  3. temperatureat reflux overnight
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified firstly by chromatography (CH2Cl2:CH3OH, 100:1)

Sources & evidence

ORD record
ord-03b643b85d0f4a8aabf8514ca2c19bd9
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

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