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

HRID 1186522Notes

Reaction equation

HRID 1186522 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.[Cl:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH2:27][NH2:28].CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.CC([O-])(C)C.[Na+]>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].O1CCOCC1>[Cl:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH2:27][NH:28][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

Participants

7

Reactant 4

HCID 666482-ChlorobenzylamineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86670919HCID 86670919, compound

Product 1

HCID 66548833(2-Chloro-benzyl)-{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

Conditions

Temperature
100 °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) (0.187 g, 0.5 mmol), 2-chloro-benzylamine (71 mg, 0.5 mmol), Pd2(dba)3 (30 mg), Davephos (40 mg), NaOtBu (70 mg, 0.73 mmol) and dioxane (20 mL) in a sealed tube was bubbled with N2 for several minutes and then heated under N2 at 100° C. for 15 hours. The solution was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The obtained crude product was purified by preparative-HPLC. The obtained product was dissolved in ethanol and then concentrated HCl (1 mL) was added and stirred for 1 h. The mixture was concentrated under reduced pressure. The resulting solid was suspended in dichloromethane and concentrated to give (2-chloro-benzyl)-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl}-pyridin-2-yl]-amine; hydrochloride. (Yield 47 mg). 1HNMR (300 MHz, CD3OD): δ 8.39 (d, 1H, J=5.4 Hz), 8.17 (s, 1H), 7.73 (t, 1H, J=7.8 Hz), 7.40-7.36 (m, 2H), 7.22-7.09 (m, 4H), 6.87 (d, 1H, J=8.4 Hz), 5.43 (brs, 2H), 4.64 (s, 2H), 3.86-3.66 (m, 4H), 3.41-3.37 (m, 2H), 2.91 (s, 3H). LC-MS: [M+H]+ 435.

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 obtained crude product
  6. customwas purified by preparative-HPLC
  7. dissolutionThe obtained product was dissolved in ethanol
  8. additionconcentrated HCl (1 mL) was added
  9. concentrationThe mixture was concentrated under reduced pressure
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b0071f5d14954b80a8357593918c2066
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

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