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

HRID 2367492
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HRID 2367492 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][CH:22]=[C:21]([F:25])[CH:20]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28](F)[CH:27]=2)[N:3]=1.CCO.CCN(C(C)C)C(C)C.[NH2:47][NH2:48]>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][CH:22]=[C:21]([F:25])[CH:20]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:26]2[CH:31]=[C:30]3[C:29]([C:32]([NH2:33])=[N:47][NH:48]3)=[CH:28][CH:27]=2)[N:3]=1
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참가 물질

7

반응물 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504504(3S,6R)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-[(3-fluorophenyl)methyl]-6-methyl-3-piperidinecarboxamide

생성물 1

HCID 58504506(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-[(3-fluorophenyl)methyl]-6-methyl-3-piperidinecarboxamide수율 45.5%

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-[(3-fluorophenyl)methyl]-6-methyl-3-piperidinecarboxamide (201 mg, 0.435 mmol), 5 mL of EtOH, Hunig's base (0.304 mL, 1.738 mmol), and hydrazine anhydrous (0.082 mL, 2.61 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, washed by water, and dried in vacuum. The solid was recrystallized using CH3CN, and the solid in the solvent was filtered, washed by EtOAc and CH3CN, and dried in vacuum to afford the title compound (94 mg) as a light yellow solid. LC-MS (ES) m/z=475 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.16 (m, 3H), 1.60-1.92 (m, 4H), 2.29-2.44 (m, 1H), 2.84-3.07 (m, 1H), 4.20-4.45 (m, 2H), 5.36 (s, 2H), 6.08 (s, 2H), 6.60 (s, 1H), 7.10 (m, 3H), 7.32-7.50 (m, 1H), 7.54-7.63 (m, 1H), 7.70 (s, 1H), 7.95 (s, 1H), 8.49-8.59 (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. customThe solid was recrystallized
  6. filtrationthe solid in the solvent was filtered
  7. washwashed by EtOAc and CH3CN
  8. customdried in vacuum

출처 및 근거

ORD 기록
ord-57afb24679da45c68f72e5fd60dfa4aa
출처 데이터셋
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08697685B2

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