Dichloromethane → HCID 57964916, compound

HRID 1931700Notes

Reaction equation

HRID 1931700 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].[CH3:24][O:25][C:26]1[C:31]([OH:32])=[CH:30][CH:29]=[C:28]([O:33][CH3:34])[N:27]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>CN(C)C=O.O>[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]([O:32][C:31]4[C:26]([O:25][CH3:24])=[N:27][C:28]([O:33][CH3:34])=[CH:29][CH:30]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 40479467HCID 40479467, compoundHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Product 1

HCID 57964916HCID 57964916, compoundYield 29.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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; 50 mg, 0.15 mmol), 2,6-dimethoxy-pyridin-3-ol (Aagile Labs Division of Tyger Scientific, Ewing, N.J., USA; 30 mg, 0.19 mmol), and potassium carbonate (27 mg, 0.2 mmol) in dimethylformamide (2 mL) was heated in the microwave oven at 160° C. for 10 min. Dichloromethane and water were added, and the aqueous layer was extracted twice with dichloromethane. The dichloromethane layers were combined, evaporated, and purified by preparative C18 HPLC, eluting with 10-100% acetonitrile/water to give 4-[4-(2,6-dimethoxy-pyridin-3-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (20 mg, 29%) as an off-white powder. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.96-2.04 (m, 2H), 2.18-2.30 (m, 2H), 2.90-3.05 (m, 2H), 3.90 (s, 3H), 3.95 (s, 3H), 4.25-4.38 (m, 2H), 4.90-5.00 (m, 1H), 6.37 (d, 1H, J=8.2 Hz), 7.41 (d, 1H, J=8.2 Hz), 8.03 (s, 1H), 8.50 (s, 1H). Mass spectrum MH+=457. HRMS Calcd. For C22H29N6O5 (MH+): 457.2194. Found: 457.2193.

Workup

  1. extractionthe aqueous layer was extracted twice with dichloromethane
  2. customevaporated
  3. custompurified by preparative C18 HPLC
  4. washeluting with 10-100% acetonitrile/water

Sources & evidence

ORD record
ord-79cdc0f3510048dba6c11e347caf3b1b
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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