Sodium Carbonate → N-(5-(2-amino-6-methyl-4-pyrimidinyl)-2-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

HRID 1431307Notes

Reaction equation

HRID 1431307 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([NH:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[N:25][C:26]=1[N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)=[C:5]([CH3:19])[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)=[N:7]2.Cl[C:37]1[CH:42]=[C:41]([CH3:43])[N:40]=[C:39]([NH2:44])[N:38]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>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>[NH2:44][C:39]1[N:38]=[C:37]([C:23]2[CH:22]=[C:21]([NH:20][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]=[CH:17][CH:16]=[CH:15][N:14]=4)[C:5]=3[CH3:19])[C:26]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[N:25][CH:24]=2)[CH:42]=[C:41]([CH3:43])[N:40]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 218102-Amino-4-chloro-6-methylpyrimidineHCID 312751,4-DioxaneHCID 596311135-(5,7-Difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-6-morpholinopyridin-3-ylboronic acid

Product 1

HCID 59631544N-(5-(2-amino-6-methyl-4-pyrimidinyl)-2-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 5-(5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-6-morpholinopyridin-3-ylboronic acid (0.026 mmol, described herein), 4-chloro-6-methylpyrimidin-2-amine (3.7 mg, 0.026 mmol), sodium carbonate (8.18 mg, 0.077 mmol), dichlorobis(triphenylphosphine)palladium(ii) (1.8 mg, 2.57 μmol), 1,4-dioxane (560 μL) and water (140 μL) heated in a microwave at 120° C. for 60 min. The reaction was then cooled to rt and partitioned between EtOAc and water. The organic layer was dried (magnesium sulfate) and concentrated, and chromatography afforded N-(5-(2-amino-6-methyl-4-pyrimidinyl)-2-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.72-8.81 (1H, m), 8.52-8.61 (1H, m), 7.85-7.96 (2H, m), 7.61-7.71 (1H, m), 7.52-7.61 (1H, m), 7.47-7.52 (1H, m), 7.41 (1H, m), 7.03 (1H, m), 6.84-6.93 (1H, m), 5.22 (2H, br. s.), 3.94 (4H, br. s.), 3.45-3.73 (2H, m), 3.00-3.40 (2H, br. s.), 2.33-2.52 (3H, m), 2.15-2.29 (3H, m). Mass Spectrum (ESI) m/e=541.0 (M+1).

Workup

  1. temperatureThe reaction was then cooled to rt
  2. custompartitioned between EtOAc and water
  3. dry with materialThe organic layer was dried (magnesium sulfate)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-289d49ae7f6e49ca873e85607b080bf6
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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