Triethylamine → 2-[(E)-1-[3-[1-(6-fluoro-1-methylindazol-5-yl)ethyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]oxyethanol

HRID 1892372ノート

反応式

HRID 1892372 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[CH:4][C:3]=1[CH:12]([C:14]1[N:18]2[N:19]=[C:20]([C:23](=O)[CH3:24])[CH:21]=[CH:22][C:17]2=[N:16][CH:15]=1)[CH3:13].Cl.[NH2:27][O:28][CH2:29][CH2:30][OH:31].C(N(CC)CC)C>CO>[OH:31][CH2:30][CH2:29][O:28]/[N:27]=[C:23](/[C:20]1[CH:21]=[CH:22][C:17]2[N:18]([C:14]([CH:12]([C:3]3[CH:4]=[C:5]4[C:9](=[CH:10][C:2]=3[F:1])[N:8]([CH3:11])[N:7]=[CH:6]4)[CH3:13])=[CH:15][N:16]=2)[N:19]=1)\[CH3:24]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 22507086Ethanol, 2-(aminooxy)-, hydrochlorideHCID 581905981-(3-(1-(6-Fluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazin-6-yl)ethanone

生成物 1

HCID 509915362-[(E)-1-[3-[1-(6-fluoro-1-methylindazol-5-yl)ethyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]oxyethanol収率 18%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
30 °C

実験手順

To a solution of 1-(3-(1-(6-fluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazin-6-yl)ethanone (100 mg, 0.267 mmol) in methanol (10 mL) was added 2-(aminooxy)ethanol hydrochloride (30.3 mg, 0.267 mmol). Triethyl amine was added dropwise to adjust the pH to 5˜6. The reaction mixture was stirred at 30° C. for 20 h. The solvent was removed in vacuo and the residue was dissolved in DCM, washed with NaHCO3 (aq) and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to afford the crude product which was purified by chromatography on silica gel to afford 19 mg (17%) of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.01 (d, 1H), 7.91 (s, 1H), 7.77 (s, 1H), 7.58 (d, 1H), 7.50 (s, 1H), 7.49 (d, 1H), 4.91 (q, 1H), 4.76 (t, 1H), 4.20 (t, 2H), 3.95 (s, 3H), 3.65 (m, 2H), 2.13 (s, 3H), 1.76 (d, 3H). LCMS (method B): [MH]+=397, tR=2.50 min. Chiral separation (method K) provided enantiomeric pure compounds example 39-R and example 39-S.

後処理

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in DCM
  3. washwashed with NaHCO3 (aq) and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product which
  7. customwas purified by chromatography on silica gel

出典と根拠

ORDレコード
ord-66973886196745419e4734d2ea47e41a
出典データセット
uspto-grants-2013_08
特許番号
US08507676B2

反応ノート

読み込み中…