Sodium Carbonate → 8-(1-Ethyl-propyl)-2,6-dimethyl-3-(3-methyl-4-pyridin-3-yl-thiophen-2-yl)-imidazo[1,2-b]pyridazine

HRID 1432605ノート

反応式

HRID 1432605 の反応式
Br[C:2]1[C:3]([CH3:23])=[C:4]([C:7]2[N:11]3[N:12]=[C:13]([CH3:21])[CH:14]=[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:10]3=[N:9][C:8]=2[CH3:22])[S:5][CH:6]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[C:26](B(O)O)[CH:25]=1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].C(O)CC>[CH2:17]([CH:16]([C:15]1[C:10]2[N:11]([C:7]([C:4]3[S:5][CH:6]=[C:2]([C:26]4[CH:25]=[N:24][CH:29]=[CH:28][CH:27]=4)[C:3]=3[CH3:23])=[C:8]([CH3:22])[N:9]=2)[N:12]=[C:13]([CH3:21])[CH:14]=1)[CH2:19][CH3:20])[CH3:18]

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343783-Pyridinylboronic acidHCID 579329703-(4-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

生成物 1

HCID 579330888-(1-Ethyl-propyl)-2,6-dimethyl-3-(3-methyl-4-pyridin-3-yl-thiophen-2-yl)-imidazo[1,2-b]pyridazine収率 20.3%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 10311-Propanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

A solution of 3-(4-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.25 g, 0.64 mmol), pyridine-3-boronic acid (0.086 g, 0.70 mmol), 2 M Na2CO3 (0.48 mL, 0.96 mmol) and, n-PrOH (3 mL), is degassed with nitrogen for 10 minutes. Pd(OAc)2 (2.7 mg, 0.0013 mmol) and PPh3 (0.010 g, 0.038 mmol) are added and the solution is heated at 90° C. overnight. The solution is diluted with EtOAc (30 mL), washed with 10% Na2CO3 (30 mL), water (30 mL), brine (30 mL), dried over MgSO4, filtered, and concentrated. The residue is purified by ISCO (20-40% EtOAc gradient) furnish the title compound (0.051 g, 0.13 mmol, 20%). 1H NMR (CDCl3) δ 0.88 (t, J=7.5 Hz, 6H), 1.74-1.92 (m, 4H), 2.09 (s, 3H), 2.50 (s, 3H), 2.52 (s, 3H), 3.29-3.40 (m, 1H), 6.69 (s, 1H), 7.33-7.43 (m, 1H), 7.47 (s, 1H), 7.80 (d, J=7.9 Hz, 1H), 8.61 (bs, 1H), 8.78 (bs, 1H). LC/MS (m/z): calcd. for C23H26N4S (M+H)+: 391.2; found: 391.4.

後処理

  1. washwashed with 10% Na2CO3 (30 mL), water (30 mL), brine (30 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO (20-40% EtOAc gradient)

出典と根拠

ORDレコード
ord-7e650bfc0dbe44a4b1175ac9aa7da9f1
出典データセット
uspto-grants-2009_11
特許番号
US07612067B2

反応ノート

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