Potassium Carbonate → HCID 68226471, compound

HRID 1186552Notes

Reaction equation

HRID 1186552 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].[C:32]([O:36][C:37](=[O:49])[NH:38][CH2:39][CH2:40][CH:41]([NH2:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)([CH3:35])([CH3:34])[CH3:33].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: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:48][CH:41]([C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)[CH2:40][CH2:39][NH:38][C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:49])[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 11430Potassium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 57826906HCID 57826906, compoundHCID 86670921{4-[3-(6-Bromo-pyridin-2-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

Product 1

HCID 68226471HCID 68226471, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
130 °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) (0.487 g, 1.0 mmol), (3-amino-3-phenyl-propyl)-carbamic acid tert-butyl ester (from Example 53 supra) (0.375 g, 1.5 mmol), Pd2(dba)3 (60 mg), Davephos (80 mg), K2CO3 (207 mg, 1.5 mmol) in dioxane (25 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:MeOH, 100:1), then by preparative-HPLC to give (4-{3-[6-(3-tert-butoxycarbonylamino-1-phenyl-propylamino)-pyridin-2-yl]-imidazo[1,2-a]pyrazin-8-ylamino}-cyclohexyl)-carbamic acid tert-butyl ester. (Yield 250 mg). LC-MS: [M+H]+ 657.

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:MeOH, 100:1)

Sources & evidence

ORD record
ord-faad66cd3fce45d2a66c4ca2a56a8a0b
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

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