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Lithium iodide → 2-(6-(Methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol

HRID 1027170
ノート
印刷プレビュー

反応式

HRID 1027170 の反応式
C[O:2][C:3]1[CH:8]=[C:7]([C:9]2[O:10][C:11]([CH3:14])=[CH:12][N:13]=2)[CH:6]=[CH:5][C:4]=1[C:15]1[N:20]=[N:19][C:18]([N:21]([CH3:32])[CH:22]2[CH2:27][C:26]([CH3:29])([CH3:28])[NH:25][C:24]([CH3:31])([CH3:30])[CH2:23]2)=[CH:17][CH:16]=1.[Li+].[I-]>N1C(C)=CC(C)=CC=1C.CO.CCOC(C)=O.O>[CH3:32][N:21]([CH:22]1[CH2:27][C:26]([CH3:29])([CH3:28])[NH:25][C:24]([CH3:31])([CH3:30])[CH2:23]1)[C:18]1[N:19]=[N:20][C:15]([C:4]2[CH:5]=[CH:6][C:7]([C:9]3[O:10][C:11]([CH3:14])=[CH:12][N:13]=3)=[CH:8][C:3]=2[OH:2])=[CH:16][CH:17]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 2

HCID 66321Lithium iodideHCID 867105626-(2-methoxy-4-(5-methyloxazol-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

生成物 1

HCID 1362530162-(6-(Methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol収率 48.4%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water
溶媒
HCID 79532,4,6-Trimethylpyridine溶媒
HCID 8857Ethyl Acetate溶媒

反応条件

温度
170 °C

実験手順

To a solution of 6-(2-methoxy-4-(5-methyloxazol-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (106 mg, 0.24 mmol) in 2,4,6 collidine (8 mL, dried over MgSO4, and filtered), was added anhydrous LiI (292 mg, 2.18 mmol). The reaction was stirred at 170° C. for 4 h, then cooled and diluted with small amounts of MeOH and EtOAc (150 mL) and H2O (30 mL). The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified via HPLC to provide 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol (49 mg). LCMS Rt=0.55 min (LCMS method Q); MS (M+1)=422.3. 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.12 (d, J=9.9 Hz, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.53 (dd, J=6.1, 1.8 Hz, 1H), 7.51 (s, 1H), 7.30 (d, J=10.1 Hz, 1H), 6.92 (d, J=1.0 Hz, 1H), 5.03-5.14 (m, 1H), 3.01 (s, 3H), 2.43 (d, J=1.2 Hz, 3H), 1.68 (dd, J=12.6, 3.5 Hz, 2H), 1.56 (t, J=12.3 Hz, 2H), 1.37 (s, 6H), 1.21 (s, 6H).

後処理

  1. temperaturecooled
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified via HPLC

出典と根拠

ORDレコード
ord-43690465ac034d20a0a49f08377b3a97
出典データセット
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08729263B2

反応ノート

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