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

HRID 2367484
ノート
印刷プレビュー

反応式

HRID 2367484 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][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]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][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]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 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504619(3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(cyclohexylmethyl)-6-methyl-3-piperidinecarboxamide

生成物 1

HCID 46215129(3S,6R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-(cyclohexylmethyl)-6-methyl-3-piperidinecarboxamide収率 59.9%

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]-N-(cyclohexylmethyl)-6-methyl-3-piperidinecarboxamide (187 mg, 0.415 mmol), 5 mL of EtOH, Hunig's base (0.290 ml, 1.66 mmol), and hydrazine anhydrous (0.078 ml, 2.49 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 being heavier than yellow solution. Water (20 mL) was added to the yellow solution, and a solid formed. The solid was filtered and washed by water, dried in vacuum, and then treated with EtOAc and CH3OH. The solid in the solvent was filtered, washed by EtOAc, and dried in vacuum to afford the title compound (115 mg) as a light yellow solid. LC-MS (ES) m/z=463 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.88 (m, 2H), 1.05-1.26 (m, 6H), 1.32-1.46 (m, 1H), 1.54-1.74 (m, 8H), 1.75-1.88 (m, 1H), 2.21-2.38 (m, 1H), 2.76-3.08 (m, 3H), 5.38 (s, 2H), 6.07 (s, 2H), 6.57 (s, 1H), 7.54-7.59 (m, 1H), 7.66-7.72 (m, 1H), 7.87-7.92 (m, 1H), 7.94 (s, 1H), 11.50 (s, 1H).

後処理

  1. customa solid formed
  2. filtrationThe solid was filtered
  3. washwashed by water
  4. customdried in vacuum
  5. additiontreated with EtOAc and CH3OH
  6. filtrationThe solid in the solvent was filtered
  7. washwashed by EtOAc
  8. customdried in vacuum

出典と根拠

ORDレコード
ord-b93616c6eccb4c41a8eb467b67d2f835
出典データセット
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08697685B2

反応ノート

読み込み中…

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