Dichloromethane → 3-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-6-[(6-methylpyridin-3-yl)methyl]benzo[h]quinazolin-4(3H)-one

HRID 82441

반응식

HRID 82441 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][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])=[CH:4][CH:3]=1.[Cl-].C[Zn+].[CH2:34](Cl)Cl>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:29][C@@H:24]1[C@@H:23]([N:13]2[C:12](=[O:30])[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]4=[C:9]([CH2:8][C:5]4[CH:6]=[N:7][C:2]([CH3:34])=[CH:3][CH:4]=4)[CH:10]=3)[N:15]=[CH:14]2)[CH2:28][CH2:27][O:26][CH2:25]1

참가 물질

6

반응물 3

HCID 6344DichloromethaneHCID 510006176-[(6-chloropyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-oneHCID 178477797HCID 178477797, 화합물

생성물 1

HCID 510006183-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-6-[(6-methylpyridin-3-yl)methyl]benzo[h]quinazolin-4(3H)-one

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
50 °C

실험 절차

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (Example 1, 0.040 g, 0.095 mmol) in 1 mL of THF under an atmosphere of nitrogen was added methyl zinc chloride (0.095 mL, 2 M in THF, 1.90 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), 1:1 complex with DCM (3 mol %). The reaction was heated at 50° C. for 18 h, cooled to rt, and quenched with water (2 mL). The mixture was filtered through celite and the aqueous layer was extracted 2× with dichloromethane. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 10-60% ethyl acetate in hexanes, to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 401.46 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 8.92 (d, J=7.5 Hz, 1H), 8.38 (s, 1H), 8.29 (s, 1H), 7.83 (d, J=7.3 Hz, 1H), 7.79 (s, 1H), 7.66-7.59 (m, 2H), 7.15 (d, J=8.1 Hz, 1H), 6.90 (d, J=7.9 Hz, 1H), 4.87-4.78 (m, 1H), 4.26-4.19 (m, 4H), 4.12-4.08 (m, 1H), 3.81 (br s, 1H), 3.61-3.54 (m, 1H), 3.44-3.37 (m, 1H), 2.43 (s, 3H), 2.33-2.23 (m, 1H), 2.03-1.99 (m, 1H).

후처리

  1. temperaturecooled to rt
  2. customquenched with water (2 mL)
  3. filtrationThe mixture was filtered through celite
  4. extractionthe aqueous layer was extracted 2× with dichloromethane
  5. dry with materialThe combined organic fractions were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel chromatography
  9. washeluting with 10-60% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-6e922bd8d561444a811506cacae4afba
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846702B2

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