HCID 71014126, 화합물 → HCID 71014159, 화합물

HRID 1430081노트

반응식

HRID 1430081 반응식
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2([F:36])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[C:24]4[C:19](=[C:20]([F:25])[CH:21]=[CH:22][CH:23]=4)[N:18]=[C:17]([C:26]([NH:28][C@H:29]4[CH2:34][CH2:33][CH2:32][CH2:31][C@@H:30]4[OH:35])=[O:27])[CH:16]=3)[CH2:10][CH2:9]2)[CH:3]=1.[CH3:37][Zn]C>C1COCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:19]=1[N:18]=[C:17]([C:26]([NH:28][C@H:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C@@H:30]1[OH:35])=[O:27])[CH:16]=[C:15]2[CH2:14][N:11]1[CH2:12][CH2:13][C:8]([F:36])([C:4]2[CH:3]=[C:2]([CH3:37])[CH:7]=[CH:6][N:5]=2)[CH2:9][CH2:10]1

참가 물질

6

반응물 2

HCID 71014126HCID 71014126, 화합물HCID 178477796HCID 178477796, 화합물2회

생성물 1

HCID 71014159HCID 71014159, 화합물

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매2회HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

To a solution of 4-{[4-(4-chloropyridin-2-yl)-4-fluoropiperidin-1-yl]methyl}-8-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide (Example C) (0.022 g, 0.043 mmol) in THF (3 mL) under an atmosphere of nitrogen was added dimethyl zinc (2.0 M in THF, 0.043 mL, 0.085 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.0011 mg, 0.00090 mmol). The reaction was heated to 90° C., cooled to RT, and retreated with additional dimethyl zinc (2.0 M in THF, 0.043 mL, 0.085 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.0011 mg, 0.00090 mmol). The reaction was heated to 100° C. for 5 h, then at 50° C. for an additional 16 h. The mixture was cooled to RT, diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate and brine. The organic solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant residue was purified via silica gel chromatography eluting with 0-5% MeOH in dichloromethane to provide the title compound (Example D) as a white solid that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 495.1 for M+H+. 1H NMR (400 MHz, CDCl3) δ 8.39-8.36 (m, 2H), 8.30-8.20 (m, 2H), 7.69-7.38 (m, 3H), 7.00 (br s, 1H), 4.03 (s, 2H), 3.89 (br s, 1H), 3.59-3.49 (m, 1H), 3.48-3.14 (m, 1H), 2.85-2.81 (m, 2H), 2.61-2.57 (m, 2H), 2.44-2.37 (m, 2H), 2.37 (s, 3H), 2.18-2.13 (m, 2H), 1.87-1.79 (m, 4H), 1.50-1.14 (m, 4H).

후처리

  1. temperaturecooled to RT
  2. temperatureThe reaction was heated to 100° C. for 5 h
  3. temperatureThe mixture was cooled to RT
  4. washwashed with saturated aqueous sodium bicarbonate and brine
  5. dry with materialThe organic solution was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified via silica gel chromatography
  9. washeluting with 0-5% MeOH in dichloromethane

출처 및 근거

ORD 기록
ord-69a2dc7f56ff48b7a543de2ed4568672
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940765B2

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