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Cesium carbonate → 3-[(1S,2S)-2-Hydroxycyclohexyl]-6-{[6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl]methyl}pyrido[3,4-h]quinazolin-4(3H)-one

HRID 1183826
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HRID 1183826 반응식
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][N:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:37][N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]1>C1COCC1.C(OCC)(=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[OH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@@H:23]1[N:13]1[C:12](=[O:30])[C:11]2[C:16](=[C:17]3[CH:22]=[CH:21][N:20]=[CH:19][C:18]3=[C:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([C:41]4[CH:40]=[N:39][N:38]([CH3:37])[CH:42]=4)=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1
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참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2회HCID 532612286-[(6-Chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one

생성물 1

HCID 532346763-[(1S,2S)-2-Hydroxycyclohexyl]-6-{[6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl]methyl}pyrido[3,4-h]quinazolin-4(3H)-one

시약·촉매·용매 3

HCID 178418851
HCID 178418851, 화합물
촉매
2회
HCID 8028Tetrahydrofuran용매
HCID 8857Ethyl Acetate용매

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온도
85 °C

실험 절차

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one (Example 1, 0.070 g, 0.17 mmol) in 2 mL of THF under an atmosphere of nitrogen was added cesium carbonate (0.33 mL, 1 N aqueous, 0.33 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.052 g, 0.19 mmol), and bis(tri-tert-butylphosphine)palladium(0) (10 mol %). The reaction was heated at 85° C. for 20 h, and additional 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.040 g, 0.19 mmol), and bis(tri-tert-butylphosphine)palladium(0) (7.0 mg, 0.014 mmol) were added. After 5 h, the reaction was cooled to rt, diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate and brine. The solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-10% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 466.9 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 9.64 (s, 1H), 9.03 (d, J=6.0 Hz, 1H), 8.80 (d, J=5.4 Hz, 1H), 8.65 (s, 1H), 8.59 (s, 1H), 8.35 (s, 1H), 8.19 (s, 2H), 8.13 (s, 1H), 8.00 (d, J=8.4 Hz, 1H), 4.18 (br s, 1H), 3.99 (s, 2H), 3.31 (s, 3H), 2.20 (br s, 1H), 2.00 (br s, 2H), 1.87 (br s, 2H), 1.52-1.39 (m, 4H).

후처리

  1. temperaturethe reaction was cooled to rt
  2. washwashed with saturated aqueous sodium bicarbonate and brine
  3. dry with materialThe solution was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via silica gel chromatography
  7. washeluting with 0-10% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-33c300d23d524499837a10932f23036e
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08664387B2

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