Sodium Carbonate → 4-[4-(4-Chloro-2-cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931658Notes

Reaction equation

HRID 1931658 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22](Cl)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:24][C:25]1[CH:26]=[CH:27][C:28]([OH:33])=[C:29]([CH:32]=1)[C:30]#[N:31].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:33][C:28]4[CH:27]=[CH:26][C:25]([Cl:24])=[CH:32][C:29]=4[C:30]#[N:31])=[C:17]3[CH:16]=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 27774205-Chloro-2-hydroxybenzonitrileHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Product 1

HCID 579650194-[4-(4-Chloro-2-cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 60 mg, 0.178 mmol), 5-chloro-2-hydroxybenzonitrile (Maybridge, Tintagel, Cornwall, UK; 28 mg, 0.178 mmol), and potassium carbonate (54 mg, 0.392 mmol) in dimethylformamide (1 mL) was heated in the microwave oven at 160° C. for 10 min. Saturated sodium carbonate solution was added to the reaction mixture and the resulting precipitate was filtered through a silica gel plug, eluting with methanol. The solvent was removed and the residue was purified by HPLC to give 4-[4-(4-chloro-2-cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (19 mg, 24%) as a white solid. Mass spectrum MH+=455. 1H NMR (300 MHz, DMSO-d6) δ 1.41 (s, 9H), 1.96-2.04 (m, 4H), 2.96-3.08 (m, 2H), 4.02-4.12 (m, 2H), 4.96-5.06 (m, 1H), 7.69 (d, 1H, J=8.7 Hz), 7.94 (dd, 1H, J=2.6, 8.9 Hz), 8.25 (d, 1H, J=2.4 Hz), 8.50 (s, 1H), 8.57 (s, 1H).

Workup

  1. filtrationthe resulting precipitate was filtered through a silica gel plug
  2. washeluting with methanol
  3. customThe solvent was removed
  4. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-fe7fdad3719b4b3cb411794a61d6874c
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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