Sodium Bicarbonate → HCID 67338716, compound

HRID 1668959Notes

Reaction equation

HRID 1668959 reaction equation
I[C:2]1[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1.[CH3:24][N:25]1[C:30]2[N:31]=[C:32]([NH:35][CH3:36])[N:33]=[CH:34][C:29]=2[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[C:26]1=[O:46].O.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CN(C=O)C>[CH3:24][N:25]1[C:30]2[N:31]=[C:32]([NH:35][CH3:36])[N:33]=[CH:34][C:29]=2[CH:28]=[C:27]([C:2]2[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][N:6]=[C:7]3[NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)[C:26]1=[O:46]

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 2735133Sodium Carbonate MonohydrateHCID 58466448HCID 58466448, compoundHCID 673385755-iodo-6-methyl-N-(3-(trifluoromethyl)phenyl)isoquinolin-1-amine

Product 1

HCID 67338716HCID 67338716, compoundYield 19.8%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 5-iodo-6-methyl-N-(3-(trifluoromethyl)phenyl)isoquinolin-1-amine (0.1680 g, 0.392 mmol) in 10:1 DMF:Water (1.5 ml), charged to a 5 mL microwave reaction vessel, 8-methyl-2-(methylamino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one (0.149 g, 0.471 mmol), dichlorobis(triphenyl-phosphine)palladium (ii) (0.0110 g, 0.0157 mmol), and sodium carbonate hydrate (0.102 g, 0.824 mmol) were added. The reaction mixture was stirred at 160° C. for 20 min. The reaction mixture was diluted with EtOAc and partioned with saturated sodium bicarbonate. The aqueous layer was extracted twice with EtOAc. The combined organics were washed with brine, dried over magnesium sulfate and concentrated under vacuum. The resulting residue was loaded on to silica and purified by silica gel chromatography (ISCO 2×12.0 g, 0-6% MeOH in DCM, 45 min.) and HPLC to give 8-methyl-6-(6-methyl-1-(3-(trifluoromethyl)phenylamino)isoquinolin-5-yl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (0.0381 g, 19.8% yield). MS (M+H)+ 491.

Workup

  1. extractionThe aqueous layer was extracted twice with EtOAc
  2. washThe combined organics were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under vacuum
  5. custompurified by silica gel chromatography (ISCO 2×12.0 g, 0-6% MeOH in DCM, 45 min.) and HPLC

Sources & evidence

ORD record
ord-c665eb1075484174a0a79b6793f6531e
Source dataset
uspto-grants-2011_08
Patent number
US07989461B2

Reaction notes

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