Dichloromethane → 5-Hexynyl-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochloride

HRID 2305116Notes

Reaction equation

HRID 2305116 reaction equation
[C:1]([C:7]1[CH:8]=[C:9]([O:13][CH2:14][C@@H:15]2[CH2:18][CH2:17][N:16]2C(OC(C)(C)C)=O)[CH:10]=[N:11][CH:12]=1)#[C:2][CH2:3][CH2:4][CH2:5][CH3:6].C(Cl)[Cl:27]>C(O)(C(F)(F)F)=O>[ClH:27].[ClH:27].[C:1]([C:7]1[CH:8]=[C:9]([O:13][CH2:14][C@@H:15]2[CH2:18][CH2:17][NH:16]2)[CH:10]=[N:11][CH:12]=1)#[C:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 698309175-Hexynyl-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

Product 1

HCID 98617545-Hexynyl-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochlorideYield 96%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 5-hexynyl-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 58a (102 mg, 0.26 mmol) in CH2Cl2 (2 mL) and TFA (1 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(73 mg, 96% yield). MS (CI/NH3) m/z 279 (M+H)+. 1HH NMR (CDCl3, 300 MHz) δ: 0.96 (t, J=7.0 Hz, 3H), 1.43-1.61 (m, 2H), 2.21-2.44 (m, 4H), 2.48 (t, J=7.5 Hz, 2H), 3.44-3.52 (m, 1H), 3.68-3.80 (m, 1H), 3.96-4.09 (m, 2H), 4.25-4.35 (m, 1H), 7.28 (d, J=3.0 Hz, 1H), 7.99 (d, J=3.0 Hz, 1H). The base was treated with HCl in EtOH to afford the hydrochloride salt (73 mg). mp 103-105° C. MS (CI/NH3) m/z 279 (M+H)+. 1H NMR (D2O, 300 MHz) δ 0.98 (t, J=7.4, 3H), 1.48-1.72 (m, 4H), 2.55-2.60 (m, 2H), 2.68-2.77 (m, 2H), 4.07-4.24 (m, 2H), 4.44-4.48 (m, 2H), 4.80-4.99 (m, 1H), 7.66 (d, J=2.7, 1H), 8.14 (d, J=3.1, 1H). Anal. Calcd for C15H19N2O.1.6 HCl: C, 53.44; H, 6.16; N, 8.31. Found: C, 53.81; H, 5.77; N, 8.43. [α]25D=−7.5° (c 0.2, 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-f877e8786c9e409f8ea5d931a556dc2a
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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