Toluene → HCID 25122895, compound

HRID 1931636Notes

Reaction equation

HRID 1931636 reaction equation
FC(F)(F)C(O)=O.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([N:21]2[C:25]3=[N:26][CH:27]=[N:28][C:29]([O:30][C:31]4[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=4)=[C:24]3[CH:23]=[N:22]2)[CH2:17][CH2:16]1)=[O:14])(C)([CH3:10])[CH3:9].ClC(OC(C)C)=O.C1(C)C=CC=CC=1.C(N(CC)CC)C>ClCCl.O>[CH:8]([O:12][C:13]([N:15]1[CH2:16][CH2:17][CH:18]([N:21]2[C:25]3=[N:26][CH:27]=[N:28][C:29]([O:30][C:31]4[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=4)=[C:24]3[CH:23]=[N:22]2)[CH2:19][CH2:20]1)=[O:14])([CH3:10])[CH3:9]

Participants

8

Reactant 5

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 44622155HCID 44622155, compound

Product 1

HCID 25122895HCID 25122895, compoundYield 104.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (3 mL) was added to a solution of 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Example 92; 300 mg, 0.7 mmol) in dichloromethane (12 mL). The solution was stirred at room temperature for 30 min and then the solvents were evaporated, first using house vacuum and then high vacuum. Dichloromethane (10 mL) was added to the residue, and then a solution of isopropyl chloroformate in toluene (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 1 M; 1.1 mL, 1.1 mmol) was added at room temperature, followed by triethylamine (480 mg, 4.7 mmol). The mixture was stirred for 2 h at room temperature and then water was added. The layers were separated and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were evaporated, and purified by silica gel column chromatography, eluting with 0-80% ethyl acetate/hexanes) to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (291 mg, 100%) as a viscous oil. 1H NMR (300 MHz, CDCl3) δ 1.28 (d, 6H, J=6.4 Hz), 2.00-2.03 (m, 1H), 2.24-2.30 (m, 2H), 2.46 (s, 3H), 2.95-3.04 (m, 2H), 4.27-4.39 (m, 2H), 4.93-5.00 (m, 2H), 7.28-7.32 (m, 1H), 7.52-7.55 (m, 1H), 8.07 (s, 1H), 8.48-8.52 (m, 2H). Mass spectrum MH+=397. HRMS Calcd. For C20H25N6O3 (MH+): 397.1983. Found: 397.1982.

Workup

  1. customthe solvents were evaporated
  2. additionDichloromethane (10 mL) was added to the residue
  3. stirringThe mixture was stirred for 2 h at room temperature
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice with dichloromethane
  6. customThe combined organic layers were evaporated
  7. custompurified by silica gel column chromatography
  8. washeluting with 0-80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-73454f710bfe42379b3c5f5563d1db13
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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