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

HRID 2367577노트

반응식

HRID 2367577 반응식
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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-3fa2a99ef6924a01bffe9f31c9bd4c17
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697685B2

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