Hydrochloric Acid → HCID 89813167, 화합물

HRID 1481106노트

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HRID 1481106 반응식
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](Br)[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[Cl:25])[CH:10]=2)=[O:5])[CH3:2].[C:27]([Cu])#[N:28].N#N.Cl>C(Cl)Cl.CN1C(=O)CCC1>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:27]#[N:28])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[Cl:25])[CH:10]=2)=[O:5])[CH3:2]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 947NitrogenHCID 89812883HCID 89812883, 화합물HCID 178418546HCID 178418546, 화합물

생성물 1

HCID 89813167HCID 89813167, 화합물수율 78%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 13387N-methyl-2-pyrrolidone용매

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온도
130 °C

실험 절차

A 20-mL scintillation vial was charged with 1-bromo-4-hydroxy-7-(4-fluoro-2-chloro-phenoxy)-isoquinoline-3-carboxylic acid ethyl ester (340 mg, 0.77 mmol), CuCN (138 mg, 1.54 mmol) and NMP (1.8 mL). It was filled with N2 gas and close-capped. The mixture was stirred in a 130° C. oil bath for 3 h. Reaction mixture was diluted with CH2Cl2 (100 mL) and stirred at room temperature for 3 days. To the mixture was added 100 mL of 0.5 N HCl aq. solution. It was stirred vigorously for 3 min. Two phases were separated. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Crude product was purified by silica gel chromatography, eluting with 5-50% EtOAc/hexanes to provide the title compound 231 mg (0.60 mmol) in 78% yield. 1H NMR (200 MHz) in CDCl3, δ ppm: 12.42 (s, 1H), 8.45 (d, J=8.8 Hz, 1H), 7.54 (dd, J=9.2, 2.6 Hz, 1H), 7.40-7.10 (m, 4H), 4.58 (q, J=7.0 Hz, 2H), 1.51 (t, J=7.0 Hz, 3H).

후처리

  1. customclose-capped
  2. customReaction mixture
  3. stirringstirred at room temperature for 3 days
  4. stirringIt was stirred vigorously for 3 min
  5. customTwo phases were separated
  6. washOrganic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customCrude product was purified by silica gel chromatography
  11. washeluting with 5-50% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-9bd66f965f5746409c96cd1d2c928ccb
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409892B2

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