Cesium carbonate → 2-Bromo-6-(8-tert-butyl-5-oxo-1,2,3,5-tetrahydrobenzo[e][1,4]diazepin-4-yl)-benzaldehyde

HRID 1879673Notes

Reaction equation

HRID 1879673 reaction equation
[C:1]([C:5]1[CH:6]=[CH:7][C:8]2[C:14](=[O:15])[NH:13][CH2:12][CH2:11][NH:10][C:9]=2[CH:16]=1)([CH3:4])([CH3:3])[CH3:2].[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22](Br)[C:19]=1[CH:20]=[O:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22]([N:13]2[C:14](=[O:15])[C:8]3[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:16][C:9]=3[NH:10][CH2:11][CH2:12]2)[C:19]=1[CH:20]=[O:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 126486412,6-DibromobenzaldehydeHCID 595485328-tert-Butyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one

Product 1

HCID 595485362-Bromo-6-(8-tert-butyl-5-oxo-1,2,3,5-tetrahydrobenzo[e][1,4]diazepin-4-yl)-benzaldehyde

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

8-tert-Butyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one (420 mg, 2 mmol), 2,6-Dibromo-benzaldehyde (2.03 g, 8 mmol, 3eq), Xanthphos (22 mg, 0.02eq), and cesium carbonate (1.23 g, 4 mmol, 2 eq) were taken up in dioxane (5.0 mL) and a stream of argon gas was bubbled through the mixture for 1 minute. The catalyst Pd(dba)2 (33 mg, 0.03 eq) was added and argon was bubbled through for an additional minute. The resulting mixture was sealed under argon and stirred at 100° C. for 18 hours. The reaction was cooled and filtered. The collected solid was triturated with water and filtered to give a solid. The dioxane filtrate was combined with this solid, the solvent removed under vacuum, and the residue chromatographed, eluting with 50% ethyl acetate in hexanes gave a solid, 81 mg. (M+H)+=402.

Workup

  1. customa stream of argon gas was bubbled through the mixture for 1 minute
  2. customargon was bubbled through for an additional minute
  3. customThe resulting mixture was sealed under argon
  4. temperatureThe reaction was cooled
  5. filtrationfiltered
  6. customThe collected solid was triturated with water
  7. filtrationfiltered
  8. customto give a solid
  9. customthe solvent removed under vacuum
  10. customthe residue chromatographed
  11. washeluting with 50% ethyl acetate in hexanes
  12. customgave a solid, 81 mg

Sources & evidence

ORD record
ord-ed7acf2dedb64cccaed3e5bd00607747
Source dataset
uspto-grants-2012_11
Patent number
US08318719B2

Reaction notes

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