4-Chlorobenzylamine → HCID 68226974, compound

HRID 1186562Notes

Reaction equation

HRID 1186562 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:16]3[N:17]([C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[N:25]=4)=[CH:22][N:23]=3)[CH:18]=[CH:19][N:20]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Cl:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH2:38])=[CH:35][CH:34]=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]>[C:1]([O:5][C:6](=[O:31])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:16]3[N:17]([C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([NH:38][CH2:37][C:36]5[CH:39]=[CH:40][C:33]([Cl:32])=[CH:34][CH:35]=5)[N:25]=4)=[CH:22][N:23]=3)[CH:18]=[CH:19][N:20]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 660364-ChlorobenzylamineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86670921{4-[3-(6-Bromo-pyridin-2-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

Product 1

HCID 68226974HCID 68226974, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A mixture of {4-[3-(6-bromo-pyridin-2-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (from Example 40 supra) (0.244 g, 0.5 mmol), 4-chloro-benzylamine (0.143 g, 1.0 mmol), Pd2(dba)3 (30 mg), Davephos (40 mg), NaOtBu (100 mg, 0.1 mmol) in dioxane (12 mL) in a sealed tube was bubbled with N2 for several minutes and then heated under N2 at 110° C. for 14 hours. The solution was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by chromatography (CH2Cl2:MeOH, 100:1) to give (4-{3-[6-(4-chloro-benzylamino)-pyridin-2-yl]-imidazo[1,2-a]pyrazin-8-ylamino}-cyclohexyl)-carbamic acid tert-butyl ester. (Yield 214 mg, 78%).

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 by chromatography (CH2Cl2:MeOH, 100:1)

Sources & evidence

ORD record
ord-fe977bffe7db40a78afdfffb418c7dc1
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

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