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Chloride → 3-[(1S,2S)-2-Hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]pyrido[3,4-h]quinazolin-4(3H)-one

HRID 1183821
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HRID 1183821 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.[Cl-].[CH2:32]1COCC1>C(=O)(O)[O-].[Na+].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>[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]([CH3:32])=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1
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참가 물질

7

반응물 3

HCID 312ChlorideHCID 8028TetrahydrofuranHCID 532612286-[(6-Chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one

생성물 1

HCID 532612303-[(1S,2S)-2-Hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]pyrido[3,4-h]quinazolin-4(3H)-one

시약·촉매·용매 3

HCID 178418397
HCID 178418397, 화합물
촉매
HCID 8857Ethyl Acetate용매
HCID 516892Sodium Bicarbonate용매

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온도
90 °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, 0.030 g, 0.071 mmol) in 1 mL of THF under an atmosphere of nitrogen was added methylzine chloride (2 M in THF, 0.107 mL, 0.214 mmol) and tetrakis(triphenylphosphine)palladium(0) (3.0 mg, 0.0026 mmol). The reaction was heated at 90° C. for 3 h, cooled to rt, and diluted with saturated aqueous sodium bicarbonate and ethyl acetate. The layers were partitioned, and the organic solution was washed with brine, 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 proton NMR spectra consistent with theory and a mass ion (ES+) of 401.0 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H), 8.43 (s, 2H), 8.19 (s, 2H), 7.86 (s, 1H), 7.34-7.32 (m, 1H), 7.04 (s, 1H), 5.30 (s, 2H), 4.53-4.49 (m, 2H), 4.22 (br s, 1H), 2.49 (s, 3H), 2.32-2.29 (m, 1H), 2.04-2.01 (m, 1H), 1.91-1.89 (m, 1H), 1.58-1.46 (m, 3H).

후처리

  1. temperaturecooled to rt
  2. customThe layers were partitioned
  3. washthe organic solution was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via silica gel chromatography
  8. washeluting with 0-10% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-251bf6beea0a49f89d3c76d04d3b1cb6
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08664387B2

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