Hydrazine → (3S)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-(3,4-difluorophenyl)-3-piperidinecarboxamide

HRID 2367452노트

반응식

HRID 2367452 반응식
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=3)=[O:15])[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.CCN(C(C)C)C(C)C.[NH2:43][NH2:44]>CCO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:25]2[CH:30]=[C:29]3[C:28]([C:31]([NH2:32])=[N:43][NH:44]3)=[CH:27][CH:26]=2)[N:3]=1

참가 물질

5

반응물 3

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504756(3S)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(3,4-difluorophenyl)-3-piperidinecarboxamide

생성물 1

HCID 58504802(3S)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-(3,4-difluorophenyl)-3-piperidinecarboxamide수율 70.3%

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
150 °C

실험 절차

Into a microwave tube, (3S)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(3,4-difluorophenyl)-3-piperidinecarboxamide (90 mg, 0.199 mmol), 3 mL of EtOH, hunig's base (0.104 ml, 0.597 mmol), and hydrazine anhydrous (0.025 ml, 0.796 mmol) weres added, and the yellow mixture was heated at 150° C. for 150 minutes under microwave conditions. The solution turned black. LCMS showed mainly product. The black solids were filtered and the yellow filtrate was evaporated. The resulting yellow residue was dissolved in CH3OH, and purified by HPLC (CH3CN/H2O w/0.1% HCO2H) to afford the title compound (65 mg) as a light yellow solid. LC-MS (ES) m/z=465 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.50 (m, 1H), 1.69-1.96 (m, 2H), 2.06 (m, 1H), 3.19 (m, 1H), 3.40-3.55 (m, 1H), 4.36-4.56 (m, 2H), 4.73-4.97 (m, 1H), 6.91-7.09 (m, 1H), 7.25-7.52 (m, 4H), 7.66-8.03 (m, 4H), 10.25-10.42 (m, 1H), 10.33 (d, J=8.8 Hz, 1H), 12.09 (s, 2H).

후처리

  1. filtrationThe black solids were filtered
  2. customthe yellow filtrate was evaporated
  3. dissolutionThe resulting yellow residue was dissolved in CH3OH
  4. custompurified by HPLC (CH3CN/H2O w/0.1% HCO2H)

출처 및 근거

ORD 기록
ord-2b31357a539e47f5b4206ea9c8a75393
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697685B2

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