Ammonium formate → tert-Butyl (1-pyridazin-3-ylpiperidin-4-yl)carbamate

HRID 2239571

반응식

HRID 2239571 반응식
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>CO.[Pd]>[N:7]1[CH:2]=[CH:3][CH:4]=[C:5]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:18])[CH3:20])[CH2:10][CH2:9]2)[N:6]=1

참가 물질

5

반응물 2

HCID 2723923Ammonium formate2회HCID 379672514-(Boc-amino)-1-(6-chloro-3-pyridazinyl)piperidine

생성물 1

HCID 86625871tert-Butyl (1-pyridazin-3-ylpiperidin-4-yl)carbamate수율 57%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매

반응 조건

온도
0 °C

실험 절차

tert-Butyl [1-(6-chloropyridazin-3-yl)piperidin-4-yl]carbamate (0.5 g, 1.60 mmol) was dissolved in MeOH (20 ml) and cooled to 0° C. with an icebath. 10% Pd/C (60 mg) was added carefully. Ammonium formate (0.30 g, 4.80 mmol) was added and the reaction mixture was heated to 40° C. Ammonium formate (0.604 g, 9.59 mmol) was added in portions during the reaction, after 33 h at 40° C. the reaction mixture was filtered through celite and the celite was washed with MeOH (20 ml). The reaction mixture was evaporated and the residue was diluted with EtOAc (100 mL) and washed with water (200 ml). The organic phase was dried (Na2SO4) filtered and evaporated. The residue was purified by silica gel column chromatography using a 98:2 mixture of DCM:MeOH to give the title compound as a solid (0.25 g, 57%). 1H NMR (CDCl3, 500 MHz): δ 8.52-8.47 (m, 1H), 7.17-7.11 (m, 1H), 6.91-6.84 (m, 1H), 4.67-4.57 (m, 1H), 4.30-4.21 (m, 2H), 3.75-3.62 (m, 1H), 3.09-2.99 (m, 2H), 2.05-1.96 (m, 2H), 1.46-1.35 (m, 2H), 1.40 (s, 9H); 13C NMR (CDCl3, 125 MHz): δ 160.0, 155.4, 143.3, 127.5, 112.7, 79.6, 48.2, 44.3, 32.1, 28.6.

후처리

  1. temperaturethe reaction mixture was heated to 40° C
  2. filtrationwas filtered through celite
  3. washthe celite was washed with MeOH (20 ml)
  4. customThe reaction mixture was evaporated
  5. additionthe residue was diluted with EtOAc (100 mL)
  6. washwashed with water (200 ml)
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by silica gel column chromatography
  11. additiona 98:2 mixture of DCM

출처 및 근거

ORD 기록
ord-57fb08bb8e0d40bca6d0a5b4a23dc707
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723333B2

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