Dichloromethane → HCID 90409751, compound

HRID 589113Notes

Reaction equation

HRID 589113 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:21]2[C:22]([CH3:27])=[N:23][O:24][C:25]=2[CH3:26])[C:5]2[O:10][CH2:9][C@H:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)[N:7]3[C:17](=[O:20])[NH:18][C:19]=1[C:6]=23.[CH3:28][C:29]1(C)C(C)(C)OB(C=C)O1.ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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]>[CH3:27][C:22]1[C:21]([C:4]2[C:5]3[O:10][CH2:9][C@H:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=4)[N:7]4[C:17](=[O:20])[NH:18][C:19]([C:6]=34)=[C:2]([CH:28]=[CH2:29])[CH:3]=2)=[C:25]([CH3:26])[O:24][N:23]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 90409730HCID 90409730, compound

Product 1

HCID 90409751HCID 90409751, compoundYield 64.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (4S)-9-bromo-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one (3.00 g, 7.02 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (2.14 mL, 12.6 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (570 mg, 0.70 mmol) and potassium carbonate (2.90 g, 21 mmol) in 1,4-dioxane (40 mL) and water (20 mL) was heated at 80° C. for 1 h. The mixture was then poured over water and extracted with ethyl acetate. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by flash column chromatography (40% ethyl acetate/hexanes to 90% ethyl acetate/hexanes) gave the desired product (1.69 g, 64%) as a single enantiomer. LCMS calculated for C21H19N4O3 (M+H)+: m/z=375.1. found: 375.1.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extracts were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (40% ethyl acetate/hexanes to 90% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-b7b38121355440a6ba92e57d7249467d
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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