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

HRID 1186568Notes

Reaction equation

HRID 1186568 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][N:15]=[C:16]([NH:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:4][CH:3]=1.[C:26]([O:30][C:31](=[O:44])[NH:32][CH2:33][CH2:34][CH:35]([NH2:43])[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=1)([CH3:29])([CH3:28])[CH3:27].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:26]([O:30][C:31](=[O:44])[NH:32][CH2:33][CH2:34][CH:35]([C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=1)[NH:43][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]([NH:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[C:11]3=[N:10][CH:9]=2)[N:7]=1)([CH3:29])([CH3:27])[CH3:28]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 68106814HCID 68106814, compoundHCID 86670920HCID 86670920, compound

Product 1

HCID 68226779(3-(3-Chloro-phenyl)-3-{6-[8-(2-morpholin-4-yl-ethylamino)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-ylamino}-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)-imidazo[1,2-a]pyrazin-8-yl]-(2-morpholin-4-yl-ethyl)-amine (from Example 41 supra) (0.403 g, 1.0 mmol), [3-amino-3-(3-chloro-phenyl)-propyl]-carbamic acid tert-butyl ester (from Example 62 supra) (0.427 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. overnight. The solution was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by preparative-HPLC to give (3-(3-chloro-phenyl)-3-{6-[8-(2-morpholin-4-yl-ethylamino)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-ylamino}-propyl)-carbamic acid tert-butyl ester. (Yield 50 mg). LC-MS: 607 [M+H]+ 607.

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 preparative-HPLC

Sources & evidence

ORD record
ord-5f2f4655fb0f41e89538e6b948376246
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

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