Water → Mk-7622

HRID 1183143Notes

Reaction equation

HRID 1183143 reaction equation
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

Participants

7

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 46208126HCID 46208126, compoundHCID 178477797HCID 178477797, compound

Product 1

HCID 46207733Mk-7622

Reagents, catalysts & solvents 2

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

Conditions

Temperature
50 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-d1cb807465414e9894a32a93c043c01d
Source dataset
uspto-grants-2014_03
Patent number
US08664234B2

Reaction notes

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