Ethanol → (3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-(3-methylcyclohexyl)-3-piperidinecarboxamide

HRID 2367500ノート

反応式

HRID 2367500 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH:20]([CH3:24])[CH2:19]3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27](F)[CH:26]=2)[N:3]=1.CCO.CCN(C(C)C)C(C)C.[NH2:46][NH2:47]>O.CO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH:20]([CH3:24])[CH2:19]3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:25]2[CH:26]=[C:27]3[C:28]([C:31]([NH2:32])=[N:46][NH:47]3)=[CH:29][CH:30]=2)[N:3]=1

参加物

7

反応物 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504608HCID 58504608、化合物

生成物 1

HCID 58504522(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-(3-methylcyclohexyl)-3-piperidinecarboxamide収率 17.8%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

反応条件

温度
110 °C

実験手順

Into a microwave tube, (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-(3-methylcyclohexyl)-3-piperidinecarboxamide (186.2 mg, 0.413 mmol), 5 mL of EtOH, Hunig's base (0.289 ml, 1.653 mmol), and hydrazine anhydrous (0.078 mL, 2.480 mmol) were added, and the yellow suspension mixture was heated overnight at 110° C. in an oil bath. LCMS showed mainly product. CH3OH (5 mL) was added to the solution. The black solid and the yellow solution were carefully separated due to the black solid is heavier than yellow solution. Water (20 mL) was added to the yellow solution, and a solid formed. The solid was filtered, washed by water, and dried in vacuum. The solid was recrystallized using CH3CN, and the solid in the solvent was filtered, washed by EtOAc and CH3CN, and dried in vacuum to afford the light yellow title compound (34 mg). LC-MS (ES) m/z=463 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.67-0.94 (m, 6H), 0.97-1.33 (m, 6H), 1.36-1.87 (m, 7H), 2.13-2.42 (m, 1H), 2.90 (m, 1H), 3.45-3.63 (m, 1H), 4.67 (m, 2H), 5.38 (s, 2H), 6.07 (s, 2H), 6.57 (s, 1H), 7.57 (dd, J=8.6, 1.0 Hz, 1H), 7.70 (m, 2H), 7.94 (s, 1H), 11.49 (s, 1H).

後処理

  1. customa solid formed
  2. filtrationThe solid was filtered
  3. washwashed by water
  4. customdried in vacuum
  5. customThe solid was recrystallized
  6. filtrationthe solid in the solvent was filtered
  7. washwashed by EtOAc and CH3CN
  8. customdried in vacuum

出典と根拠

ORDレコード
ord-7e5b9c4a67864d8cb3bce67b7521dd3a
出典データセット
uspto-grants-2014_04
特許番号
US08697685B2

反応ノート

読み込み中…