5-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine → 5-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochloride

HRID 365857Notes

Reaction equation

HRID 365857 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=[CH:8][C:9]2[CH:10]=[C:11]([O:16][CH2:17][C@@H:18]3[CH2:21][CH2:20][N:19]3C(OC(C)(C)C)=O)[CH:12]=[N:13][C:14]=2[Cl:15])=[CH:3][CH:2]=1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[ClH:15].[ClH:15].[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=[CH:8][C:9]2[CH:10]=[C:11]([O:16][CH2:17][C@@H:18]3[CH2:21][CH2:20][NH:19]3)[CH:12]=[N:13][C:14]=2[Cl:15])=[CH:3][CH:2]=1

Participants

4

Reactant 1

HCID 538519835-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

Product 1

HCID 867508145-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochlorideYield 186.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 5-(2-(4-Pyridinyl)ethenyl)-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 89a (176 mg) in CH2Cl2 (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 CHCl3 :MeOH:NH4OH 10:1:0.1 to afford the free base of the title compound (102 mg, 79% yield). MS (CI/NH3) m/z 302 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ2.24-2.48 (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, J1=1.0 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 EtOH 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, SH), 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 CHCl3 :MeOH:NH4OH 10:1:0.1

Sources & evidence

ORD record
ord-db97e97d8bd340d9a562e6224297b3c2
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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