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

HRID 706847

反応式

HRID 706847 の反応式
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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-72f5bbf20e1e4a2fb0d011f19aef1de5
出典データセット
uspto-grants-2015_11
特許番号
US09174996B2

関連ノート

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