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

HRID 2367594ノート

反応式

HRID 2367594 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][CH2:20][CH:19]3[CH3:24])=[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]>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][CH2:20][CH:19]3[CH3:24])=[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

6

反応物 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504821HCID 58504821、化合物

生成物 1

HCID 58504758(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-(2-methylcyclohexyl)-3-piperidinecarboxamide収率 61.9%

試薬・触媒・溶媒 1

HCID 887Methanol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-(2-methylcyclohexyl)-3-piperidinecarboxamide (192 mg, 0.426 mmol), EtOH (5 mL), Hunig's base (0.074 ml, 0.426 mmol), and hydrazine anhydrous (0.08 mL, 2.56 mmol) were added, and the yellow suspension mixture was heated overnight at 110° C. in an oil bath. When the temperature of the reaction reached to 100° C., the solid in the mixture was all dissolved. After overnight, there was a yellow solution as well as a little amount of black colored solid formed. LCMS showed mainly product. CH3OH (5 mL) was added to the solution. The black solid was filtered from the yellow solution. Water (20 mL) was added to the yellow solution, and a solid was formed. The solid was filtered, washed by water, and dried in vacuum. The solid was recrystallized from CH3CN, and the solid was filtered, washed by CH3CN, and dried in vacuum to afford the title compound (122 mg) as a light yellow solid. LC-MS (ES) m/z=463 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.68-0.98 (m, 4H), 1.14 (m, 8H), 1.66 (m, 8H), 2.25 (m, 1H), 3.30 (m, 1H), 3.36 (m, 1H), 5.38 (s, 2H), 6.07 (s, 2H), 6.56 (d, J=3.5 Hz, 1H), 7.51-7.65 (m, 1H), 7.70 (s, 1H), 7.73 (s, H), 7.94 (d, J=2.8 Hz, 1H), 11.50 (s, 1H).

後処理

  1. customreached to 100° C.
  2. customformed
  3. filtrationThe black solid was filtered from the yellow solution
  4. additionWater (20 mL) was added to the yellow solution
  5. customa solid was formed
  6. filtrationThe solid was filtered
  7. washwashed by water
  8. customdried in vacuum
  9. customThe solid was recrystallized from CH3CN
  10. filtrationthe solid was filtered
  11. washwashed by CH3CN
  12. customdried in vacuum

出典と根拠

ORDレコード
ord-8017faf069f542288c2c62a88116aa27
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…