Trifluoroacetic acid → HCID 67403905, compound

HRID 914034Notes

Reaction equation

HRID 914034 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:16][CH2:17][C:18]3([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)[CH2:23][CH2:22][N:21]([C:24](OC(C)(C)C)=O)[CH2:20][CH2:19]3)[C:12]([O:14][CH3:15])=[O:13])[CH:10]=1)[NH:7][N:6]=[CH:5]2.[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41]>>[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:16][CH2:17][C:18]3([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[C:12]([O:14][CH3:15])=[O:13])[CH:10]=1)[NH:7][N:6]=[CH:5]2

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57546152HCID 57546152, compound

Product 1

HCID 67403905HCID 67403905, compound

Procedure

tert-butyl 4-((1-(5-chloro-1H-indazol-7-yl)-2-methoxy-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (20 mg) was dissolved in trifluoroacetic acid (20% in dichloromethane, 1.5 mL) and stirred for 20 min at room temperature. The reaction was concentrated and the resulting residues loaded onto a strong cation exchange cartridge. The cartridge was flushed with several volumes of methanol which were discarded. The amine was eluted with 2M ammonia in methanol and concentrated. The unprotected piperidine was dissolved in acetonitrile (1 mL) and treated with formalin (50 μL) and sodium cyanoborohydride (2.4 mg) and one drop of acetic acid. The reaction was stirred at room temperature for 1 h. The reaction was concentrated. The resulting residue was dissolved in trifluoroacetic acid (25% in dichloromethane, 2 mL), stirred for 5 min, and concentrated. The resulting residue was purified by preparative HPLC to afford the title compound. 1H-NMR (CD3OD, 500 MHz) δ 8.05 (m, 1H), 7.78 (m, 1H), 7.44 (m, 2H), 7.22 (m, 0.75H), 7.13 (m, 1.8H), 7.03 (m, 0.6H), 5.34 (s, 0.3H), 5.27 (s, 0.7H), 3.69 (m, 4H), 3.47 (m, 4H), 2.55-3.00 (m, 7H), 2.00-2.55 (m, 2.5H). Mass spec.: 446.24 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. customThe cartridge was flushed with several volumes of methanol which
  3. washThe amine was eluted with 2M ammonia in methanol
  4. concentrationconcentrated
  5. dissolutionThe unprotected piperidine was dissolved in acetonitrile (1 mL)
  6. additiontreated with formalin (50 μL) and sodium cyanoborohydride (2.4 mg) and one drop of acetic acid
  7. stirringThe reaction was stirred at room temperature for 1 h
  8. concentrationThe reaction was concentrated
  9. dissolutionThe resulting residue was dissolved in trifluoroacetic acid (25% in dichloromethane, 2 mL)
  10. stirringstirred for 5 min
  11. concentrationconcentrated
  12. customThe resulting residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-46ef785cb95f4a59bdc7e27faa7217bc
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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