Potassium Carbonate → HCID 178481002, compound

HRID 897593Notes

Reaction equation

HRID 897593 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)[C:3]=12.F[C:32]1[CH:39]=[CH:38][CH:37]=[C:36]([S:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=2)[C:33]=1[C:34]#[N:35].C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:32]4[CH:39]=[CH:38][CH:37]=[C:36]([S:40][C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=5)[C:33]=4[C:34]#[N:35])=[CH:13][CH:12]=3)[C:3]=12

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 44564116-Fluoro-2-(2-pyridylthio)benzenecarbonitrileHCID 178481006HCID 178481006, compound

Product 1

HCID 178481002HCID 178481002, compoundYield 68.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of cis-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenol (0.300 g, 0.736 mmol) in dimethylformamide (20 mL), was treated with 2-fluoro-6-(2-pyridylsulfanyl)benzonitrile (0.424 g, 1.84 mmol) and potassium carbonate (0.203, 1.47 mmol). The reaction mixture was stirred at 120° C. for 2 h under a nitrogen atmosphere. Ethyl acetate (125 mL) and 1 N sodium hydroxide solution (50 mL) were added to the reaction mixture. The layers were partitioned and the organic layer was washed with 1 N sodium hydroxide solution (300 mL). The organic layer was washed with water and brine (250 mL each), dried over magnesium sulfate, filtered and evaporated under reduced pressure. The solid was triturated with ethyl acetate to yield 0.310 g (68%) of cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)-6-(2-pyridylsulfanyl)benzonitrile. A warm solution of cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)-6-(2-pyridylsulfanyl)benzonitrile (0.310 g, 0.502 mmol) in ethanol was treated with a warm solution maleic acid (0.175 g, 1.503 mmol) in ethanol. A precipitate formed upon cooling and was filtered under a nitrogen atmosphere to give 0.356 g of cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)-6-(2-pyridylsulfanyl)benzonitrile bis-maleate. 1H NMR (DMSO-d6, 400 MHz) δ 8.47-8.46 (d, 1H, J=4 Hz), 8.26 (s, 1H), 7.79-7.72 (m, 4H), 7.53-7.51 (d, 1H, J=8 Hz), 7.38-7.34 (m, 3H), 7.28-7.24 (m, 2H), 6.14 (s, 4H), 4.85 (m, 1H), 3.60-3.10 (m, 7H), 3.1-2.85 (m, 2H), 2.71-2.67 (m, 2H), 2.32-2.27 (m, 3H), 2.05-1.99 (m, 2H), 1.78-1.71 (m, 4H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 5.196 min (98%).

Workup

  1. customThe layers were partitioned
  2. washthe organic layer was washed with 1 N sodium hydroxide solution (300 mL)
  3. washThe organic layer was washed with water and brine (250 mL each)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe solid was triturated with ethyl acetate

Sources & evidence

ORD record
ord-c16cda6d55d348fd90c394cc6effd9ce
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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