Sodium Bicarbonate → HCID 67338716, compound

HRID 2092317Notes

Reaction equation

HRID 2092317 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 mircowave 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 chromatgraphy (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 (.0381 g, 19.8% yield). MS (M+H)+ 491.

Workup

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

Sources & evidence

ORD record
ord-7b575bd03a194c609d95c3fe25b0bb1f
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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