Water → 1-BOC-3-(2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl)piperidine

HRID 706847Notes

Reaction equation

HRID 706847 reaction equation
Br[C:2]1[N:6]2[N:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[C:11]([N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24]#[CH:25])[CH2:19]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].CCN(C(C)C)C(C)C.O>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:11]([N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24]#[C:25][C:2]2[N:6]3[N:7]=[CH:8][CH:9]=[CH:10][C:5]3=[N:4][CH:3]=2)[CH2:19]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]

Participants

8

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 128723193-Bromoimidazo(1,2-b)pyridazineHCID 21963855tert-Butyl 3-ethynylpiperidine-1-carboxylate

Product 1

HCID 867095651-BOC-3-(2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl)piperidineYield 60%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-bromoimidazo[1,2-b]pyridazine (0.40 g, 2 mmol), 1-BOC-3-ethynylpiperidine (0.55 g, 2.6 mmol), Pd(PPh3)2Cl2 (70 mg, 0.1 mmol), CuI (29 mg, 0.15 mmol), and DIPEA (0.39 g, 3 mmol) in DMF (20 mL) was stirred at 80° C. under Ar2 for 6 hrs. The mixture was poured into 100 mL water, extracted with EtOAc (60 mL×3), organic layer was washed with brine, dried with Na2SO4, filtered, and the filtrate was evaporated in vacuo. The crude product was purified by chromatography on silica gel (PE/EtOAc 7:3 to 3:2) to give 0.39 g product as yellow oil (60.0%). 1H NMR (300 MHz, CDCl3) δ: 8.50 (1 H, d, J=4.2 Hz), 7.98-8.08 (2 H, m), 7.13-7.17 (1 H, dd, J=4.5 and 8.7 Hz), 4.09 (1 H, brs), 3.76-3.82 (1 H, m), 3.19 (1 H, brs), 3.02-3.09 (1 H, m), 2.81-2.88 (1 H, m), 2.32 (1 H, brs), 2.11-2.15 (1 H, m), 1.67-1.81 (2 H, m), 1.46 (9 H, s). LCMS: m/z [M+H]+ 327.2112.

Workup

  1. extractionextracted with EtOAc (60 mL×3), organic layer
  2. washwas washed with brine
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. customthe filtrate was evaporated in vacuo
  6. customThe crude product was purified by chromatography on silica gel (PE/EtOAc 7:3 to 3:2)

Sources & evidence

ORD record
ord-72f5bbf20e1e4a2fb0d011f19aef1de5
Source dataset
uspto-grants-2015_11
Patent number
US09174996B2

Reaction notes

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