Trifluoroacetic acid → 5-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochloride

HRID 1780362Notes

Reaction equation

HRID 1780362 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][N:11]2C(OC(C)(C)C)=O)=[CH:4][CH:3]=1.[C:21](O)([C:23](F)(F)F)=O>C(Cl)Cl>[ClH:1].[ClH:1].[N:7]1[CH:2]=[CH:3][C:4]([CH:21]=[CH:23][C:3]2[CH:4]=[C:5]([O:8][CH2:9][C@@H:10]3[CH2:13][CH2:12][NH:11]3)[CH:6]=[N:7][C:2]=2[Cl:1])=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 105182243-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)-6-chloropyridine

Product 1

HCID 867508145-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochlorideYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-2-(4-Pyridinyl)vinyl)-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 89a (176 mg) in methylene chloride (3 mL) and TFA (1.5 mL) was stirred at room temperature for 3 hours. The solvent was removed, and the residue was chromatographed on a silica gel column, eluting with chloroform:methanol:NH4OH 10:1:0.1 to afford the free base of the title compound (102 mg, 79% yield). MS (DCI/NH3) m/z 302 (M+H)+. 1 H NMR (CDCl3, 300 MHz) δ: 2.24-2.48 (m, 2H), 3.42-2.54 (m, 1H), 3.76 (q, J=7.5 Hz, 1H), 4.02-4.17 (m, 2H), 4.26-4.39 (m, 1H), 7.0 (d, J=11.0 Hz, 1H), 7.36-7.44 (m, 2H), 7.52-7.62 (m, 2H), 8.05 (d, J=3.0 Hz, 1H), 8.58-8.73 (m, 2H). The base was treated with HCl in ethanol to afford the hydrochloride salt. mp 195°-197° C. MS (CI/NH3) m/z 302 (M+H)+. 1H NMR (D2O, 300 MHz) δ1.17 (d, J=6, 1H), 2.52-2.66 (m, 2H), 2.68-2.89 (m, 4H), 4.96-5.25 (m, 5H), 6.97-7.12 (m, 1H), 7.33 (d, J=3, 1H), 7.48-7.54 (m, 1H), 7.86-7.95 (m, 1H), 8.04-8.22 (m, 2H), 8.44-8.53 (m, 1H), 8.63-8.71 (m, 1H). Anal. Calcd for C16H16N3OCl·1.5 C6H8O7 ·0.5 H2O: C, 50.13; H, 4.88; N, 7.01. Found: C, 49.95; H, 4.80; N, 7.31. [α]25D =-1.14° (c 0.18, MeOH).

Workup

  1. customThe solvent was removed
  2. customthe residue was chromatographed on a silica gel column
  3. washeluting with chloroform:methanol:NH4OH 10:1:0.1

Sources & evidence

ORD record
ord-7aa15205fa884e11b862fef57c72d3ae
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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