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

HRID 2367486노트

반응식

HRID 2367486 반응식
[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][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[C:29](F)[CH:28]=2)[N:3]=1.CCO.CCN(C(C)C)C(C)C.[NH2:48][NH2:49]>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][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:27]2[CH:28]=[C:29]3[C:30]([C:33]([NH2:34])=[N:48][NH:49]3)=[CH:31][CH:32]=2)[N:3]=1

참가 물질

7

반응물 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504502(3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-{[4-(methyloxy)phenyl]methyl}-3-piperidinecarboxamide

생성물 1

HCID 58504803(3S,6R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-{[4-(methyloxy)phenyl]methyl}-3-piperidinecarboxamide수율 48.3%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

반응 조건

온도
110 °C

실험 절차

Into a microwave tube, (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-{[4-(methyloxy)phenyl]methyl}-3-piperidinecarboxamide (203 mg, 0.43 mmol), 5 mL of EtOH, Hunig's base (0.30 mL, 1.71 mmol), and hydrazine anhydrous (0.080 mL, 2.56 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 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 (101 mg) as a light yellow solid. LC-MS (ES) m/z=487 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.07-1.22 (m, 3H), 1.56-1.94 (m, 4H), 2.33 (m, 1H), 2.94 (m, 1H), 3.74 (s, 3H), 4.10-4.22 (m, 1H), 4.23-4.37 (m, 1H), 5.38 (s, 2H), 6.08 (s, 2H), 6.58 (s, 1H), 6.83-6.97 (m, 2H), 7.20 (d, J=8.6 Hz, 2H), 7.57 (dd, J=8.6, 1.26 Hz, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.98 (s, 1H) 8.36-8.48 (m, 1H), 11.50 (s, 1H).

후처리

  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

출처 및 근거

ORD 기록
ord-d144d9b77dea4baf87713236d7c077c6
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697685B2

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