Sodium Bicarbonate → HCID 67340553, compound

HRID 1668961Notes

Reaction equation

HRID 1668961 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 microwave 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. extractionThe aqueous layer was extracted with EtOAc twice
  2. washThe combined organics were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe resulting residue was purified by HPLC

Sources & evidence

ORD record
ord-4598a44ed37d4e3bbee713074120dc63
Source dataset
uspto-grants-2011_08
Patent number
US07989461B2

Reaction notes

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