Ammonium formate → tert-butyl 7-(4-hydroxy-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

HRID 1020656

반응식

HRID 1020656 반응식
C([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:28][N:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:36])[CH:10]=1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[Pd]>[OH:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:28][N:27]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:36])[CH:10]=1

참가 물질

5

반응물 2

HCID 2723923Ammonium formateHCID 57950332tert-Butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

생성물 1

HCID 68657574tert-butyl 7-(4-hydroxy-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매

반응 조건

온도
90 °C

실험 절차

To a solution of tert-butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (0.98 g, 2.0 mmol) in CH3OH (30 mL) was added 5% Pd/C (0.3 g) and ammonium formate (0.32 g, 5.1 mmol) under an atmosphere of argon. The reaction was stirred at 90° C. until complete. The reaction mixture was cooled and filtered through a layer of Celite. The solvent was removed under reduced pressure to give tert-butyl 7-(4-hydroxy-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate, which was used directly in the next step. To a solution of tert-butyl 7-(4-hydroxy-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (800 mg, 2.02 mmol) in THF (10 mL) was added LiN(SiMe3)2 (1.0 M in THF, 2.6 mL, 2.6 mmol) followed by PhN(Tf)2 (0.94 g, 2.6 mmol) under an atmosphere of argon. The reaction was stirred at room temperature until complete. The solvent was removed under reduced pressure, and the residue was purified by flash column chromatography (silica gel, hexanes/EtOAc, 1:1) to give the title compound (0.42 g, 40% yield) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.57-7.53 (m, 2H), 7.30 (d, J=1.5 Hz, 1H), 7.02-6.99 (m, 1H), 6.60 (d, J=2.7 Hz, 1H), 6.27 (dd, J=7.8, 2.7 Hz, 1H), 4.65 (s, 2H), 3.85 (m, 2H), 3.65 (s, 3H), 2.84 (m, 2H), 1.51 (s, 9H); ESI MS m/z 528 [M+H]+.

후처리

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered through a layer of Celite
  3. customThe solvent was removed under reduced pressure

출처 및 근거

ORD 기록
ord-a5e8bf6918a74744a8b41b34540c1e9e
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716308B2

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