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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
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HRID 1027170 반응식
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
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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

생성물 1

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

시약·촉매·용매 4

HCID 887Methanol용매HCID 962
Water
용매
HCID 79532,4,6-Trimethylpyridine용매
HCID 8857Ethyl Acetate용매

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온도
170 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-43690465ac034d20a0a49f08377b3a97
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08729263B2

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