Water → 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-6-chloro-3-ethoxy-2-[5-(methylsulfonyl)pyridin-3-yl]benzonitrile

HRID 1499739Notes

Reaction equation

HRID 1499739 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[CH:21]=[C:20]([Cl:22])[C:17]([C:18]#[N:19])=[C:16](Br)[C:15]=3[O:24][CH2:25][CH3:26])[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.[CH3:27][S:28]([C:31]1[CH:32]=[N:33][CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=1)(=[O:30])=[O:29].C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].O.ClCCl>>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[CH:21]=[C:20]([Cl:22])[C:17]([C:18]#[N:19])=[C:16]([C:35]4[CH:34]=[N:33][CH:32]=[C:31]([S:28]([CH3:27])(=[O:30])=[O:29])[CH:36]=4)[C:15]=3[O:24][CH2:25][CH3:26])[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12

Participants

7

Reactant 6

HCID 962WaterHCID 6342AcetonitrileHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 533985305-(Methylsulfonyl)pyridine-3-boronic acid pinacol esterHCID 866776684-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile

Product 1

HCID 866776694-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-6-chloro-3-ethoxy-2-[5-(methylsulfonyl)pyridin-3-yl]benzonitrileYield 20%

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile (20 mg, 0.04 mmol) and 3-(methylsulfonyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (19 mg, 0.069 mmol) in acetonitrile (2 mL, 40 mmol) was added sodium carbonate (10 mg, 0.09 mmol) in water (0.5 mL, 30 mmol). The reaction was degassed with bubbling nitrogen. [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (2 mg, 0.002 mmol) was added and degassed more with N2. Reaction was heated at 100° C. for 2 hours. The crude product was purified on preparative LC-MS (acetonitrile, water, TFA) to give the desired product (0.004 g, 20%) as white amorphous solid. The product was isolated as a racemic mixture. LCMS calculated for C23H22ClN7O3S (M+H)+: m/z=512.1; found: 512.2. 1H NMR (500 MHz, DMSO) δ 9.20 (d, J=2.1 Hz, 1H), 9.12 (d, J=1.9 Hz, 1H), 8.61 (t, J=2.0 Hz, 1H), 8.12 (s, 1H), 7.80 (s, 1H), 6.36 (q, J=7.0 Hz, 1H), 3.54 (dt, J=14.0, 7.0 Hz, 1H), 3.37 (s, 3H), 3.36-3.30 (m, 1H), 2.58 (s, 3H), 1.81 (d, J=7.0 Hz, 3H), 0.92 (t, J=6.9 Hz, 3H).

Workup

  1. customThe reaction was degassed with bubbling nitrogen
  2. customdegassed more with N2
  3. customReaction
  4. customThe crude product was purified on preparative LC-MS (acetonitrile, water, TFA)

Sources & evidence

ORD record
ord-c3e8fba63764409593801d75e58bdc2a
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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