Trifluoroacetic acid → HCID 57964941, compound

HRID 1931712Notes

Reaction equation

HRID 1931712 reaction equation
FC(F)(F)C(O)=O.C([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)(C)C.ClC(O[CH2:42][CH:43]([CH3:45])[CH3:44])=O.C(N(CC)CC)C>ClCCl.O>[CH2:42]([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])[CH:43]([CH3:45])[CH3:44]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 44622155HCID 44622155, compound

Product 1

HCID 57964941HCID 57964941, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 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; 50 mg, 0.12 mmol) in dichloromethane (2 mL). The solution was stirred at room temperature for 30 min and then the solvents were evaporated using high vacuum. Dichloromethane (4 mL) was added to the residue, and then isobutyl chloroformate (available from Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 25 mg, 0.18 mmol) was added at room temperature, followed by triethylamine (80 mg, 0.79 mmol). The mixture was stirred overnight 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 preparative C18 HPLC, eluting with 10-100% acetonitrile/water to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isobutyl ester (31 mg, 63%) as a powder. 1H NMR (300 MHz, CDCl3) δ 0.97 (d, 6H, J=6.5 Hz), 1.90-2.06 (m, 3H), 2.20-2.35 (m, 2H), 2.45 (s, 3H), 2.95-3.10 (m, 2H), 3.90 (d, 2H, J=6.3 Hz), 4.32-4.48 (m, 2H), 4.95-5.10 (m, 1H), 7.26-7.72 (m, 1H), 7.50-7.54 (m, 1H), 8.07 (s, 1H), 8.45-8.60 (m, 2H). Mass spectrum MH+=411. HRMS Calcd. For C21H27N6O3 (MH+): 411.2139. Found: 411.2138.

Workup

  1. customthe solvents were evaporated
  2. additionDichloromethane (4 mL) was added to the residue
  3. stirringThe mixture was stirred overnight 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 preparative C18 HPLC
  8. washeluting with 10-100% acetonitrile/water

Sources & evidence

ORD record
ord-8bce56c0f9c049e395ecf64021588112
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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