Water → Mk-7622

HRID 1183143ノート

反応式

HRID 1183143 の反応式
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

参加物

7

反応物 4

HCID 962WaterHCID 6344DichloromethaneHCID 46208126HCID 46208126、化合物HCID 178477797HCID 178477797、化合物

生成物 1

HCID 46207733Mk-7622

試薬・触媒・溶媒 2

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

反応条件

温度
50 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-d1cb807465414e9894a32a93c043c01d
出典データセット
uspto-grants-2014_03
特許番号
US08664234B2

反応ノート

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