Cesium carbonate → HCID 66741757, compound

HRID 1256207Notes

Reaction equation

HRID 1256207 reaction equation
Cl[C:2]1[C:3]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:4]=2[N:5]([CH3:21])[C:6](=[O:20])[CH:7]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH3:17])=[C:12]([CH2:18][CH3:19])[CH:11]=2)[N:8]=1.[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.O.CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[Cl:26][C:24]1[CH:23]=[CH:22][C:4]2[N:5]([CH3:21])[C:6](=[O:20])[CH:7]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([CH2:16][CH3:17])=[C:12]([CH2:18][CH3:19])[CH:11]=3)[N:8]=[C:2]([C:31]3[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=3)[C:3]=2[CH:25]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 2856454-Fluorophenylboronic acidHCID 66741519HCID 66741519, compound

Product 1

HCID 66741757HCID 66741757, compoundYield 52.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A 10 mL sealed tube was charged with (E)-5,7-dichloro-3-(3,4-diethylbenzyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (0.25 g, 0.505 mmol, 1 equivalent), 4-fluorophenylboronic acid (0.071 g, 0.505 mmol, 1 equivalent), Pd(OAc)2, (0.2 equivalents), PPh3 (0.2 equivalents), Cs2CO3 (2 equivalents) and DMF (3 mL). The tube was evacuated, flushed with nitrogen gas and placed in an oil bath at 100° C. for 1.5 hour. The mixture was cooled to ambient temperature, diluted with ethyl acetate (10 mL) and water (5 mL), and filtered through a pad of celite. The layers were separated and the organic phase was washed with brine (3×10 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (silica gel, 70:30 hexanes:ethyl acetate) to provide an oil. This oil was dissolved in a mixture of acetonitrile (3 mL) and water (1 mL), and the solution was freeze-dried overnight to give (Z)-7-chloro-3-(3,4-diethylbenzyl)-5-(4-fluorophenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (0.12 g, 43%) as an off-white solid: mp 54-56° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.41-7.22 (m, 4H), 7.18-6.98 (m, 6H), 6.87 (d, J=8.6 Hz, 2H), 6.60 (d, J=4.6 Hz, 2H), 5.66 (d, J=15 Hz, 1H), 4.56 (d, J=15 Hz, 1H), 3.82-3.77 (m, 1H), 3.70 (s, 3H), 3.63-3.55 (m, 2H), 2.67-2.58 (m, 4H), 1.26-1.12 (m, 6H); APCI MS m/z 556 [M+H+].

Workup

  1. customA 10 mL sealed tube
  2. customThe tube was evacuated
  3. customflushed with nitrogen gas
  4. additiondiluted with ethyl acetate (10 mL) and water (5 mL)
  5. filtrationfiltered through a pad of celite
  6. customThe layers were separated
  7. washthe organic phase was washed with brine (3×10 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography (silica gel, 70:30 hexanes:ethyl acetate)
  12. customto provide an oil
  13. customthe solution was freeze-dried overnight

Sources & evidence

ORD record
ord-607d5420aa4346eb8a765e1146ee3fd4
Source dataset
uspto-grants-2013_06
Patent number
US08461153B2

Reaction notes

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