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

HRID 1431343Notes

Reaction equation

HRID 1431343 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[NH2:7][C:8]1[N:13]=[C:12](Cl)[CH:11]=[CH:10][N:9]=1.[F:15][C:16]1[CH:25]=[C:24]([F:26])[CH:23]=[C:22]2[C:17]=1[C:18]([NH:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[N:39][C:40]=1[N:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1)=[C:19]([CH3:33])[C:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1)=[N:21]2.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>[NH2:7][C:8]1[N:13]=[C:12]([C:37]2[CH:36]=[C:35]([NH:34][C:18]3[C:17]4[C:22](=[CH:23][C:24]([F:26])=[CH:25][C:16]=4[F:15])[N:21]=[C:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)[C:19]=3[CH3:33])[C:40]([N:41]3[CH2:42][CH2:43][O:44][CH2:45][CH2:46]3)=[N:39][CH:38]=2)[CH:11]=[CH:10][N:9]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2233322-Amino-4-chloropyrimidineHCID 596311135-(5,7-Difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-6-morpholinopyridin-3-ylboronic acid

Product 1

HCID 50906356N-(5-(2-amino-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 dichlorobis(triphenylphosphine)palladium(ii) (19.5 mg, 0.028 mmol), sodium carbonate (88 mg, 0.83 mmol), 2-amino-4-chloropyrimidine (35.9 mg, 0.28 mmol), 5-(5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-6-morpholinopyridin-3-ylboronic acid (0.28 mmol; described herein), 1,4-dioxane (6 mL), and water (1.5 mL) was heated in a microwave at 120° C. for 60 min. The reaction was then partitioned between EtOAc and water, and the organic layer dried (magnesium sulfate) and concentrated. Chromatography afforded N-(5-(2-amino-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 8.73-8.79 (1H, m), 8.58 (1H, d, J=2.3 Hz), 8.28 (1H, d, J=5.1 Hz), 7.85-7.96 (2H, m), 7.63-7.70 (1H, m), 7.48-7.59 (2H, m), 7.41 (1H, ddd, J=6.8, 4.7, 2.2 Hz), 6.98-7.10 (2H, m), 5.35 (2H, br. s.), 3.95 (4H, d, J=2.3 Hz), 3.10-3.70 (4H, m), 2.22 (3H, s). Mass Spectrum (ESI) m/e=527.2 (M+1).

Workup

  1. customThe reaction was then partitioned between EtOAc and water
  2. dry with materialthe organic layer dried (magnesium sulfate)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-976e39df228c4ef6b2b7378d220bbc13
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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