Ethanol → 6-{2-(methylamino)-6-[(2R)-2-methyl-1-pyrrolidinyl]-4-pyrimidinyl}-4-(methylthio)-1H-indazol-3-amine

HRID 2367577ノート

反応式

HRID 2367577 の反応式
F[C:2]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[CH3:21])[N:13]=[C:12]([NH:22][CH3:23])[N:11]=2)[CH:7]=[C:6]([S:24][CH3:25])[C:3]=1[C:4]#[N:5].CCO.CCN(C(C)C)C(C)C.[NH2:38][NH2:39]>O>[CH3:23][NH:22][C:12]1[N:11]=[C:10]([C:8]2[CH:9]=[C:2]3[C:3]([C:4]([NH2:5])=[N:38][NH:39]3)=[C:6]([S:24][CH3:25])[CH:7]=2)[CH:15]=[C:14]([N:16]2[CH2:20][CH2:19][CH2:18][C@H:17]2[CH3:21])[N:13]=1

参加物

6

反応物 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 585045802-fluoro-4-{2-(methylamino)-6-[(2R)-2-methyl-1-pyrrolidinyl]-4-pyrimidinyl}-6-(methylthio)benzonitrile

生成物 1

HCID 585045316-{2-(methylamino)-6-[(2R)-2-methyl-1-pyrrolidinyl]-4-pyrimidinyl}-4-(methylthio)-1H-indazol-3-amine収率 23%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

Into a sealable tube, 2-fluoro-4-{2-(methylamino)-6-[(2R)-2-methyl-1-pyrrolidinyl]-4-pyrimidinyl}-6-(methylthio)benzonitrile (86 mg, 0.241 mmol), EtOH (5 mL), Hunig's base (0.042 mL, 1.44 mmol), and hydrazine anhydrous (0.045 mL, 0.241 mmol) were added, and the yellow suspension mixture was heated overnight at 100° C. in an oil bath. After overnight, there was yellow solution as well as a little amount of white colored solid formed. LCMS showed no more starting material. The reaction was cooled to room temperature. 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 further purified by flash column chromatography. The fractions containing product were combined, and the solvent was removed under reduced pressure to afford the title compound (20.5 mg) as a white solid. LC-MS (ES) m/z=370 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.21 (d, J=6.1 Hz, 3H), 1.67 (m, 1H), 1.84-2.10 (m, 3H), 2.61 (s, 3H), 2.79-2.91 (m, 3H), 3.41-3.66 (m, 2H), 4.27 (m, 1H), 5.09 (s, 2H), 6.23 (s, 1H), 6.44 (s, 1H), 7.34-7.46 (m, 1H), 7.72 (s, 1H), 11.75 (s, 1H).

後処理

  1. customformed
  2. temperatureThe reaction was cooled to room temperature
  3. customa solid was formed
  4. filtrationThe solid was filtered
  5. washwashed by water
  6. customdried in vacuum
  7. customThe solid was further purified by flash column chromatography
  8. additionThe fractions containing product
  9. customthe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-3fa2a99ef6924a01bffe9f31c9bd4c17
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…