Tetrahydrofuran → 3-[3-chloro-5-(5-fluoro-2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432714ノート

反応式

HRID 1432714 の反応式
[Cl:1][C:2]1[CH:6]=[C:5]([C:7]2[N:8]([CH3:12])[N:9]=[CH:10][N:11]=2)[S:4][C:3]=1[C:13]1[N:17]2[N:18]=[C:19]([CH3:27])[CH:20]=[C:21]([CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[C:16]2=[N:15][C:14]=1[CH3:28].C1COCC1.[Li]C(C)(C)C.[F:39]NS(C1C=CC=CC=1)(=O)=O>CCOC(C)=O>[Cl:1][C:2]1[CH:6]=[C:5]([C:7]2[N:8]([CH3:12])[N:9]=[C:10]([F:39])[N:11]=2)[S:4][C:3]=1[C:13]1[N:17]2[N:18]=[C:19]([CH3:27])[CH:20]=[C:21]([CH:22]([CH2:23][CH3:24])[CH2:25][CH3:26])[C:16]2=[N:15][C:14]=1[CH3:28]

参加物

6

反応物 4

HCID 8028Tetrahydrofuran2 回HCID 15373214N-FluorobenzenesulfonamideHCID 579330443-[3-chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418306HCID 178418306、化合物

生成物 1

HCID 579329143-[3-chloro-5-(5-fluoro-2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine収率 22.2%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a −78° C. solution of 3-[3-chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.40 g, 0.72 mmol) and THF (8 mL) is added 1.7 M tert-BuLi (0.47 mL, 0.80 mmol). After 30 minutes the solution is transferred via a cannula into a solution of N-fluorobenzenesulfonamide (0.40 g, 1.25 mmol) and THF. After 30 minutes the solution warmed to ambient temperature. The solution is diluted with EtOAc (40 mL), washed with water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated. The solution is purified by ISCO (20%-30% EtOAc gradient) furnish the title compound (0.068 g, 0.16 mmol, 16%). 1H NMR (CDCl3) δ 0.87 (t, J=7.5 Hz, 6H), 1.71-1.93 (m, 4H), 2.53 (s, 3H), 2.54 (s, 3H), 3.26-3.36 (m, 1H), 4.08 (d J=2.7 Hz, 3H), 6.75 (s, 1H), 7.97 (s, 1H). LC/MS (m/z): calcd. for C20H22ClFN6S (M+H)+: 433.2; found: 433.2.

後処理

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

出典と根拠

ORDレコード
ord-27f279734e224bef8cef3ad1c6311f21
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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