Water → Mk-7622

HRID 1183143노트

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HRID 1183143 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][CH2:26][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.O>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[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][CH:20]=[CH:19][C:18]3=[C:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([CH3:34])=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1

참가 물질

7

반응물 4

HCID 962WaterHCID 6344DichloromethaneHCID 46208126HCID 46208126, 화합물HCID 178477797HCID 178477797, 화합물

생성물 1

HCID 46207733Mk-7622

시약·촉매·용매 2

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

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온도
50 °C

실험 절차

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]benzo[h]quinazolin-4(3H)-one (2.50 g, 5.95 mmol) in 30 mL of THF under an atmosphere of nitrogen was added methyl zinc chloride (2 M in THF, 5.95 mL, 11.09 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), 1:1 complex with DCM (0.146 g, 0.179 mmol). The reaction was heated at 50° C. for 18 h, cooled to rt, and slowly treated with water. A beige solid was removed via filtration and the aqueous layer of the filtrate 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 0-5% methanol in dichloromethane, to provide 3-[(1S,2S)-2-hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]benzo[h]quinazolin-4(3H)-one that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 400.0 for [M+H]+.

후처리

  1. temperaturecooled to rt
  2. customA beige solid was removed via filtration
  3. extractionthe aqueous layer of the filtrate was extracted 2× with dichloromethane
  4. dry with materialThe combined organic fractions were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via silica gel chromatography
  8. washeluting with 0-5% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-d1cb807465414e9894a32a93c043c01d
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08664234B2

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