Trifluoroacetic acid → HCID 57965053, compound

HRID 1931727Notes

Reaction equation

HRID 1931727 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])([CH3:11])([CH3:10])C.ClC(O[C:42]1[CH:47]=CC=C[CH:43]=1)=O.C(N(CC)CC)C>ClCCl.O>[C:8]1([O:12][C:13]([N:15]2[CH2:20][CH2:19][CH:18]([N:21]3[C:25]4=[N:26][CH:27]=[N:28][C:29]([O:30][C:31]5[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=5)=[C:24]4[CH:23]=[N:22]3)[CH2:17][CH2:16]2)=[O:14])[CH:11]=[CH:47][CH:42]=[CH:43][CH:10]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 44622155HCID 44622155, compound

Product 1

HCID 57965053HCID 57965053, compoundYield 15.5%

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, first using house vacuum and then high vacuum. Dichloromethane (4 mL) was added to the residue, and then phenyl chloroformate (23 μL, 0.18 mmol) was added, followed by triethylamine (110 μL, 0.8 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 phenyl ester (8 mg, 15%) as an oil that changed to a waxy solid on standing. 1H NMR (300 MHz, CDCl3) δ 2.08-2.17 (m, 2H), 2.34-2.52 (m, 5H), 3.06-3.34 (m, 2H), 4.42-4.58 (m, 2H), 5.02-5.10 (m, 1H), 7.14 (d, 2H, J=7.9 Hz), 7.22-7.25 (m, 1H), 7.28-7.31 (m, 1H), 7.38 (t, 2H, J=7.7 Hz), 7.52 (d, 1H, J=8.1 Hz), 8.10 (s, 1H), 8.48-8.53 (m, 2H). Mass spectrum MH+=431. HRMS Calcd. For C23H23N6O3 (MH+): 431.1826. Found: 431.1825.

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-77e1abeb56a14531a944010584b11a6d
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

Loading…