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

HRID 535862

Reaction equation

HRID 535862 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 Are 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 (1H, d, J=4.2 Hz), 7.98-8.08 (2H, m), 7.13-7.17 (1H, dd, J=4.5 and 8.7 Hz), 4.09 (1H, brs), 3.76-3.82 (1H, m), 3.19 (1H, brs), 3.02-3.09 (1H, m), 2.81-2.88 (1H, m), 2.32 (1H, brs), 2.11-2.15 (1H, m), 1.67-1.81 (2H, m), 1.46 (9H, 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-44c6b74b35764271b0e35c358e10b47d
Source dataset
uspto-grants-2014_10
Patent number
US08859553B2

Linked notes

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