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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
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HRID 2367484 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][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
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참가 물질

7

반응물 4

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

생성물 1

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

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]-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).

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-b93616c6eccb4c41a8eb467b67d2f835
출처 데이터셋
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08697685B2

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