5-Bromo-N-methoxy-N-methylpyridine-3-carboxamide → (S)-(5-bromopyridin-3-yl)[1-(2-{[tert-butyl(dimethl)silyl]oxy}-1-methylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanone

HRID 1753051노트

반응식

HRID 1753051 반응식
[Si:1]([O:8][CH2:9][CH:10]([N:12]1[C:20]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[C:14](I)=[CH:13]1)[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([Mg]Cl)(C)C.[Br:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([CH:39]=1)[C:33](N(OC)C)=[O:34]>C1COCC1>[Br:27][C:28]1[CH:39]=[C:32]([C:33]([C:14]2[C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:20]=3[N:12]([C@@H:10]([CH3:11])[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:13]=2)=[O:34])[CH:31]=[N:30][CH:29]=1

참가 물질

5

반응물 3

HCID 184722695-Bromo-N-methoxy-N-methylpyridine-3-carboxamideHCID 90093728HCID 90093728, 화합물HCID 178418918HCID 178418918, 화합물

생성물 1

HCID 131733656(S)-(5-bromopyridin-3-yl)[1-(2-{[tert-butyl(dimethl)silyl]oxy}-1-methylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanone수율 99.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-3-iodo-1H-pyrrolo[3,2-c]pyridine (Preparation 55, 16 g, 38.6 mmol) in THF (340 mL) was added iPrMgCl (23.2 mL, 46.3 mmol, 2M solution in THF) dropwise at 0° C. After stirring at this temperature for 1 hour, a solution of 5-bromo-N-methoxy-N-methylnicotinamide (11.4 g, 46.3 mmol) in THF (40 mL) was added slowly to the reaction. The reaction was warmed at room temperature and stirred for 18 hours. The reaction was quenched by the addition of water (200 mL) and the solvents removed in vacuo. The residue was diluted with water (400 mL), extracted into DCM:MeOH (95:5, 200 mL)) five times, the organic layers collected, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a gradient of 10-50% EtOAc in DCM to afford the title compound (18.3 g, 46.5%).

후처리

  1. stirringstirred for 18 hours
  2. customThe reaction was quenched by the addition of water (200 mL)
  3. customthe solvents removed in vacuo
  4. additionThe residue was diluted with water (400 mL)
  5. extractionextracted into DCM:MeOH (95:5, 200 mL)) five times
  6. customthe organic layers collected
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with a gradient of 10-50% EtOAc in DCM

출처 및 근거

ORD 기록
ord-ba890fa874b0423ab0ec950ff511e547
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09163021B2

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