Potassium Carbonate → Methyl 4-(benzyloxy)-7-(4-methoxybenzylamino)isoquinoline-3-carboxylate

HRID 1481144노트

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HRID 1481144 반응식
[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15](Br)=[CH:16][CH:17]=2)[CH:12]=[N:11][C:10]=1[C:20]([O:22][CH3:23])=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.C(Cl)Cl.O.[Cu]I>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([NH:31][CH2:30][C:29]3[CH:32]=[CH:33][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)=[CH:16][CH:17]=2)[CH:12]=[N:11][C:10]=1[C:20]([O:22][CH3:23])=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

9

반응물 4

HCID 11430Potassium CarbonateHCID 754524-MethoxybenzylamineHCID 145742L-ProlineHCID 89812966Methyl 4-(benzyloxy)-7-bromoisoquinoline-3-carboxylate

생성물 1

HCID 89812996Methyl 4-(benzyloxy)-7-(4-methoxybenzylamino)isoquinoline-3-carboxylate

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 6344Dichloromethane용매

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온도
80 °C

실험 절차

A mixture of methyl 4-(benzyloxy)-7-bromoisoquinoline-3-carboxylate (372.0 mg, 1.0 mmol), 4-methoxybenzylamine (0.2 mL, 1.5 mmol, TCI), CuI (19.0 mg, 0.1 mmol), proline (23.0 mg, 0.2 mmol) and K2CO3 (276.4 mg, 2.0 mmol) in DMSO (0.6 mL) was stirred at 80° C. for 24 hours under a nitrogen atmosphere. After cooling to room temperature, the mixture was diluted with CH2Cl2 (50 mL) and H2O (50 mL). The layers were separated and the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-30% EtOAc/CH2Cl2) to give the title compound in 137.0 mg. 1H NMR (CDCl3, 200 MHz): δ=8.82 (s, 1H), 7.96 (d, 1H, J=9.0 Hz), 7.54 (d, 2H, J=6.6 Hz), 7.42-7.27 (m, 5H), 7.05 (d, 1H, J=9.0 Hz), 6.93-6.87 (m, 3H), 5.18 (s, 2H), 4.38 (d, 2H, J=5.0 Hz), 4.00 (s, 3H), 3.82 (s, 3H).

후처리

  1. temperatureAfter cooling to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted twice with CH2Cl2
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. custompurified by flash chromatography (0-30% EtOAc/CH2Cl2)

출처 및 근거

ORD 기록
ord-37ee1b77ee70472e80e0187f6dbaf32e
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409892B2

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