Thiophenol → 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

HRID 1027167ノート

反応式

HRID 1027167 の反応式
C1(S)C=CC=CC=1.C[O:9][C:10]1[CH:15]=[C:14]([N:16]2[CH:20]=[CH:19][CH:18]=[N:17]2)[CH:13]=[CH:12][C:11]=1[C:21]1[N:26]=[N:25][C:24]([N:27]([CH3:38])[CH:28]2[CH2:33][C:32]([CH3:35])([CH3:34])[NH:31][C:30]([CH3:37])([CH3:36])[CH2:29]2)=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[CH3:38][N:27]([CH:28]1[CH2:33][C:32]([CH3:35])([CH3:34])[NH:31][C:30]([CH3:37])([CH3:36])[CH2:29]1)[C:24]1[N:25]=[N:26][C:21]([C:11]2[CH:12]=[CH:13][C:14]([N:16]3[CH:20]=[CH:19][CH:18]=[N:17]3)=[CH:15][C:10]=2[OH:9])=[CH:22][CH:23]=1

参加物

5

反応物 3

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 867105586-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

生成物 1

HCID 1362530412-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
190 °C

実験手順

As described in GENERAL METHOD 3-1, thiophenol (0.127 mL, 1.24 mmol) was added to a microwave vial containing 6-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (520 mg, 1.24 mmol) and K2CO3 (171 mg, 1.24 mmol) in NMP (5 mL). The microwave vial was evacuated and filled with N2 (2×). The reaction mixture was heated in the microwave at 190° C. for 30 min. The reaction mixture was filtered through celite (pre-packed filter funnel) washing with MeOH. The filtrate was acidified to pH 3 using 1 M HCl aqueous solution and then adsorbed onto a methanol conditioned SCX (10 g) column. The column was washed several times with methanol then eluted with 2 N ammonia in methanol solution. The product was collected and concentrated in vacuo to afford the crude product which was purified by preparative HPLC under basic conditions to provide 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol (198 mg, MS: 407.25 [M+H+], LC/MS Rt=0.53 min (LCMS method Q); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.86 (d, J=2.02 Hz, 1H), 7.71 (d, J=10.11 Hz, 1H), 7.63 (d, J=1.52 Hz, 1H), 7.54 (d, J=8.59 Hz, 1H), 7.21-7.30 (m, 2H), 6.91 (d, J=9.60 Hz, 1H) 6.31-6.41 (m, 1H), 4.76-4.95 (m, 1H), 2.89-3.01 (m, 3H), 1.62 (dd, J=12.13, 3.54 Hz, 2H), 1.34 (br. s, 2H), 1.27 (s, 6H), 1.10 (s, 6H).

後処理

  1. additionwas added to a microwave vial
  2. customThe microwave vial was evacuated
  3. additionfilled with N2 (2×)
  4. filtrationThe reaction mixture was filtered through celite (pre-packed filter funnel)
  5. washwashing with MeOH
  6. washThe column was washed several times with methanol
  7. washthen eluted with 2 N ammonia in methanol solution
  8. customThe product was collected
  9. concentrationconcentrated in vacuo
  10. customto afford the crude product which
  11. customwas purified by preparative HPLC under basic conditions

出典と根拠

ORDレコード
ord-f92a2a8b5ea643a4ac1fedd09c701e36
出典データセット
uspto-grants-2014_05
特許番号
US08729263B2

反応ノート

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