Sodium Bicarbonate → HCID 67340553, compound

HRID 2092319Notes

Reaction equation

HRID 2092319 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[C:18]([NH:23][CH3:24])[N:17]=[CH:16]4)[C:8]([CH3:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.Br[C:26]1[CH:27]=[N:28][CH:29]=[C:30]([O:32][CH:33]([CH3:35])[CH3:34])[CH:31]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.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]>[CH:33]([O:32][C:30]1[CH:31]=[C:26]([NH:1][C:2]2[C:11]3[C:6](=[C:7]([C:13]4[CH:14]=[C:15]5[C:20](=[CH:21][CH:22]=4)[N:19]=[C:18]([NH:23][CH3:24])[N:17]=[CH:16]5)[C:8]([CH3:12])=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)[CH:27]=[N:28][CH:29]=1)([CH3:35])[CH3:34]

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 105848083-Bromo-5-(propan-2-yloxy)pyridineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 58942263HCID 58942263, compound

Product 1

HCID 67340553HCID 67340553, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

To a solution 6-(1-amino-6-methylisoquinolin-5-yl)-N-methylquinazolin-2-amine (0.075 g, 0.24 mmol) in toluene (2.0 ml) charged to a 5-mL mircowave reaction vessel, 3-bromo-5-isopropoxypyridine (0.051 g, 0.24 mmol), X-Phos (0.0091 g, 0.019 mmol), tris(dibenzylideneacetone)dipalladium (o) (0.0087 g, 0.0095 mmol), and sodium tert-butoxide (0.046 g, 0.48 mmol) were added and the reaction mixture heated to 160° C. The reaction mixture was stirred at 160° C. for 1 hrs. The reaction mixture was then diluted with EtOAc and partioned with saturated aqueous sodium bicarbonate. The aqueous layer was extracted with EtOAc twice. The combined organics were washed with brine, dried over magnesium sulfate and concentrated under vacuum. The resulting residue was purified by HPLC to give 6-(1-(5-isopropoxypyridin-3-ylamino)-6-methylisoquinolin-5-yl)-N-methylquinazolin-2-amine. MS (M+H)+ 451.

Workup

  1. additionwere added
  2. extractionThe aqueous layer was extracted with EtOAc twice
  3. washThe combined organics were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe resulting residue was purified by HPLC

Sources & evidence

ORD record
ord-ce898be7b9de4fda837ddbd975fdda23
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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