Trifluoroacetic acid → HCID 57965008, compound

HRID 1931639Notes

Reaction equation

HRID 1931639 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]([O:23][C:24]4[CH:29]=[CH:28][C:27](=[O:30])[N:26]([CH3:31])[N:25]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])(C)([CH3:3])[CH3:2].FC(F)(F)C(O)=O.ClC(OC(C)C)=O.C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH: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:23][C:24]4[CH:29]=[CH:28][C:27](=[O:30])[N:26]([CH3:31])[N:25]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 57965027HCID 57965027, compound

Product 1

HCID 57965008HCID 57965008, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-[4-(1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Example 102; 120 mg, 0.28 mmol), trifluoroacetic acid (1.1 mL) and dichloromethane (5.5 mL) was stirred at room temperature for 30 min. The volatiles were evaporated under high vacuum and the residue was dissolved in dichloromethane (6 mL). Isopropyl chloroformate (1 M in toluene; 0.42 mL, 0.42 mmol) and triethylamine (254 μL, 1.8 mmol) were added and the mixture was stirred overnight at room temperature. 1 M aqueous sodium carbonate and dichloromethane were added, and the aqueous layer was extracted three times with dichloromethane. The combined organic extracts were evaporated and the residue was purified by column chromatography on silica gel, eluting with 0-4% methanol/dichloromethane, to give 4-[4-(1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (79 mg, 68%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.27 (d, 6H, J=6.0 Hz), 2.01 (d, 2H, J=10.9 Hz), 2.11-2.39 (m, 2H), 3.01 (t, 2H, J=12.8 Hz), 3.76 (s, 3H), 4.35 (br s, 2H), 4.85-5.06 (m, 2H), 7.07 (d, 1H, J=10.0 Hz), 7.23 (d, 1H, J=10.0 Hz), 8.17 (s, 1H), 8.51 (s, 1H). Mass spectrum (ES) MH+=414. HRMS Calcd. for C19H24N7O4 (MH+): 414.1885. Found: 414.1884.

Workup

  1. customThe volatiles were evaporated under high vacuum
  2. dissolutionthe residue was dissolved in dichloromethane (6 mL)
  3. stirringthe mixture was stirred overnight at room temperature
  4. extractionthe aqueous layer was extracted three times with dichloromethane
  5. customThe combined organic extracts were evaporated
  6. customthe residue was purified by column chromatography on silica gel
  7. washeluting with 0-4% methanol/dichloromethane

Sources & evidence

ORD record
ord-d30523265b9e4ebeb063bcaae04a8b3b
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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