Sodium Carbonate → N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

HRID 1431602Notes

Reaction equation

HRID 1431602 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([NH:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[N:26][CH:27]=1)=[C:5]([CH3:20])[C:6]([C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=1)=[N:7]2.[NH2:31][C:32]1[N:37]=[C:36](Cl)[CH:35]=[CH:34][N:33]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O>[NH2:31][C:32]1[N:37]=[C:36]([C:24]2[CH:23]=[C:22]([NH:21][C:4]3[C:3]4[C:8](=[CH:9][C:10]([F:12])=[CH:11][C:2]=4[F:1])[N:7]=[C:6]([C:13]4[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=4)[C:5]=3[CH3:20])[CH:27]=[N:26][CH:25]=2)[CH:35]=[CH:34][N:33]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2233322-Amino-4-chloropyrimidineHCID 596313385-(5,7-Difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-ylamino)pyridin-3-ylboronic acid

Product 1

HCID 50907185N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

A screw-cap vial was charged with 5-(5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-ylamino)pyridin-3-ylboronic acid (200 mg, 0.49 mmol), 2-amino-4-chloropyrimidine (63.8 mg, 0.49 mmol), bis(triphenylphosphine)palladium (II) chloride (34.6 mg, 0.049 mmol), sodium carbonate (157 mg, 1.48 mmol), 1,4-dioxane (4 mL), and water (1 mL). The solution was stirred at 95° C. for 30 min, and then cooled to rt. The product was extracted with EtOAc and DCM, and the combined organic layer was dried over magnesium sulfate and cond. The crude material was purified by flash-chromatography (basic alumina, 0-10% MeOH in DCM, then recrystallized in MeOH to afford N-(5-(2-aminopyrimidin-4-yl)-pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=456.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.78 (1H, s), 8.63 (1H, d, J=1.8 Hz), 8.56 (1H, d), 8.31 (1H, d, J=5.3 Hz), 8.13 (1H, d), 7.75 (1H, s), 7.70 (1H, m), 7.60 (1H, m), 7.49 (1H, m), 7.35 (1H, m), 7.09 (1H, s), 6.68 (2H, s), 2.45 (3H, s), 2.20 (3H, s).

Workup

  1. temperaturecooled to rt
  2. extractionThe product was extracted with EtOAc and DCM
  3. dry with materialthe combined organic layer was dried over magnesium sulfate and cond
  4. customThe crude material was purified by flash-chromatography (basic alumina, 0-10% MeOH in DCM
  5. customrecrystallized in MeOH

Sources & evidence

ORD record
ord-d8fd525791f841c58f2b2477bc4d190f
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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